CCT369260 (compound 1) is an orally avtive B-cell lymphoma 6 (BCL6) inhibitor with anti-tumor activity. CCT369260 (compound 1) exhibits an IC50 of 520 nM[1].
IC50 & Target
IC50: 520 nM (BCL6)[1].
体内研究 (In Vivo)
CCT369260 (compound 1, 15 mg/kg, po, single dose) significantly inhibits BCL6 in OCI-Ly1 DLBCL xenograft model[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
OCI-Ly1 DLBCL xenograft model (female SCID mice)[1].
Dosage:
15 mg/kg.
Administration:
PO, single dose.
Result:
Decreased the levels of BCL6 in the tumor observed up to 10 h after administration.
Animal Model:
Female Balb/C mice[1].
Dosage:
1 mg/kg iv and 5 mg/kg po (Pharmacokinetic Analysis).
Administration:
IV and PO
Result:
Demonstrated moderate clearance (CL 20 mL min−1 kg−1) with mean oral bioavailability of 54%.
分子量
508.99
Formula
C24H31ClF2N6O2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Benjamin R Bellenie, et al. Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders. J Med Chem. 2020 Apr 23;63(8):4047-4068.
CCT128930 is a ATP-competitive and selective inhibitor of AKT (IC50=6 nM for AKT2). CCT128930 has 28-fold selectivity over the closely related PKA kinase (IC50=168 nM) through the targeting of Met282 of AKT (Met173 of PKA-AKT chimera), as well as 20-fold selectivity over p70S6K (IC50=120 nM). Antitumor activity.
IC50 & Target[1]
Akt2
6 nM (IC50)
p70S6K
120 nM (IC50)
PKA
168 nM (IC50)
Autophagy
Apoptosis
体外研究 (In Vitro)
The GI50 values of CCT128930 for growth inhibition are 6.3 μM for U87MG human glioblastoma cells, 0.35 μM for LNCaP human prostate cancer cells, and 1.9 μM for PC3 human prostate cancer cells, all of which are PTEN-deficient human tumor cell lines[1]. CCT128930 (0.1-60 μM; 1 hour; U87MG human glioblastoma cells) shows an initial induction of AKT phosphorylation at serine 473 up to 20 μM, followed by a decreased in phosphorylation at higher concentrations[1]. CCT128930 inhibits direct substrates of AKT (Ser9 GSK3β, pThr246 PRAS40 and pT24 FOXO1/p32 FOXO3a) at ≥5 μM, and the downstream target, pSer235/236 S6RP at ≥ 10 μM, with generally constant levels of the respective total proteins and GAPDH[1]. CCT128930 (18.9 μM; U87MG human glioblastoma cells) causes an increase in phosphorylation of pSer473 AKT after 30 minutes, which is sustained for 48 hours. Total AKT protein signal decreases gradually from 8 hours to 48 hours of treatment[1]. CCT128930 (PTEN-null U87MG human glioblastoma cells; over a 24-hour time period) results in an increase in G0/G1 phase cells from 43.6% to 64.8% after 24 hours of treatment[1]. CCT128930 (0-10 μM; 24 hours) increases, but not inhibites, the phosphorylation of Akt in HepG2 and A549 cells. CCT128930 (0-20 μM; 24 hours) inhibits cell proliferation by inducing cell cycle arrest in G1 phase through downregulation of cyclinD1 and Cdc25A, and upregulation of p21, p27 and p53. CCT128930 (20 μM) triggers cell apoptosis with activation of caspase-3, caspase-9, and PARP. CCT128930 (0-20 μM; 24 hours) increases phosphorylation of ERK and JNK in HepG2 cells. CCT128930 (0-20 μM; 24 hours) activates DNA damage response of HepG2 cell characterized by phosphorylation of H2AX, ATM (ataxia-telangiectasia mutated), Chk1 and Chk2[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
CCT128930 (25 or 40 mg/kg; i.p. daily or twice daily for 5 days) shows antitumor activities in U87MG and BT474 human breast cancer xenografts[1]. Summary of the pharmacokinetic parameters of CCT128930 (25 mg/kg) in CrTacNCr-Fox1nu mice[1]
Tissue
Route
T1/2 (h)
Tmax (h)
Cmax (μM)
Vss (L)
Cl (L/h)
AUC0-∞ (µMh)
Bioavailability (%)
Plasma
i.v.
0.95
0.083
6.36
0.25
0.325
4.62
100
Plasma
i.p.
2.33
0.5
1.28
N/A
0.372
1.33
28.8
Tumor
i.p.
3.89
1
8.02
N/A
0.06*
25.8
N/A
Plasma
p.o.
0.57
0.5
0.432
N/A
0.317
0.392
8.5
*Apparent clearance.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
6-8 weeks old female CrTacNCr-Fox1nu mice[1]
Dosage:
25 mg/kg (U87MG human glioblastoma xenografts) or 40 mg/kg (BT474 human breast cancer xenografts)
Administration:
i.p. daily for 5 days (U87MG human glioblastoma xenografts); i.p. twice daily for 5 days (BT474 human breast cancer xenografts)
Result:
Giving a treated:control (T/C) ratio on day 12 of 48%. There was no weight loss associated with this regime in U87MG human glioblastoma xenografts. Had a profound antitumor effect with complete growth arrest and a T/C ratio of 29% on day 22. This regimen was associated with minimal weight loss, with a nadir of only 94.8% of the initial body weight on day 15 of treatment in BT474 human breast cancer xenografts.
分子量
341.84
Formula
C18H20ClN5
CAS 号
885499-61-6
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 33.33 mg/mL (97.50 mM; ultrasonic and warming and heat to 60°C)
[1]. Yap TA et al. Preclinical pharmacology, antitumor activity, and development of pharmacodynamic markers for the novel, potent AKT inhibitor CCT128930. Mol Cancer Ther. 2011 Feb;10(2):360-71.
[2]. Wang FZ, et al. CCT128930 induces cell cycle arrest, DNA damage, and autophagy independent of Akt inhibition. Biochimie. 2014;103:118-125.
CCT245737 is an orally active and seletive Chk1 inhibitor, with an IC50 of 1.3 nM.
IC50 & Target[1]
Chk1
1.3 nM (IC50)
Chk2
2440 nM (IC50)
ERK8
130 nM (IC50)
PKD1
298 nM (IC50)
RSK2
361 nM (IC50)
RSK1
362 nM (IC50)
FLT3
582 nM (IC50)
MARK3
698 nM (IC50)
NUAK1
711 nM (IC50)
CLK2
1370 nM (IC50)
BRSK1
1660 nM (IC50)
AMPK
2970 nM (IC50)
PHK
3470 nM (IC50)
CDK2/CyclA
3850 nM (IC50)
CDK1/CyclB
9030 nM (IC50)
体外研究 (In Vitro)
CCT245737 (10 µM) shows >80% inhibition of a panel of 124 kinases, including ERK8, PKD1, RSK2 and RSK1 with IC50s of 130, 298, 361 and 362 nM[1]. CCT245737 abrogates an VP-16-induced G2 checkpoint in HT29, SW620, MiaPaCa-2, and Calu6 cell lines, with IC50s ranging from 30 to 220 nM[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
CCT245737 (150 mg/kg p.o.) inhibits tumor growth in combination with LY 188011 (100 mg/kg iv) in HT29 colon cancer xenografts. CCT245737 (300 mg/kg, p.o.) also inhibits the LY 188011 (60 mg/kg iv) induced pSer296 CHK1 autophosphorylation at 24 h in SW620 human colon cancer xenografts[1]. CCT245737 (150 mg/kg, p.o) alone significantly inhibits tumor growth in an Eμ-Myc mouse model of human B-cell lymphocytic leukemia[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
379.34
Formula
C16H16F3N7O
CAS 号
1489389-18-5
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Osborne JD, et al. Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737). J Med Chem. 2016 Jun 9;59(11):5221-37.
[2]. Walton MI, et al. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eμ-MYC driven B-cell lymphoma.
Cell Assay [2]
Cytotoxicity is determined as the drug concentration that gives 50% inhibition of tumor cell proliferation (GI50) using a 96 h Sulforhodamine B (SRB) assay. Inhibition of intracellular CHK1 activity is measured using a cell based ELISA for the abrogation of an VP-16 induced G2 checkpoint (mitosis induction assay, MIA). The IC50 for G2 checkpoint abrogation (MIA) is determined in the presence of nocodazole using UCN01 as a positive control. The activity index (AI) is used as a measure of the compounds ability to induce mitosis relative to its toxicity (i.e., ratio of MIA IC50: 96 h SRB GI50). Routine potentiation studies are carried out using a fixed concentration (GI50) of either LY 188011 or SN38 in combination with a range of CCT245737 concentrations to determine the combination GI50 of CCT245737. The ability of CCT245737 to enhance LY 188011 or SN38 cell killing is expressed as a potentiation index (PI) equal to the ratio of the GI50 for CCT245737 alone versus the combination GI50 for CCT245737. PI values > 1 indicate potentiation of the genotoxic activity. In addition, a series of experiments is carried out using fixed, non- or minimally toxic concentrations of CCT245737 (≤GI20) with a range of different concentrations of LY 188011 or SN38 to determine the extent to which CCT245737 enhances drug cytotoxicity compared with the genotoxic agent alone, i.e. conventional PI (ratio GI50 genotoxic alone: GI50 genotoxic combined with non-toxic CCT245737 concentration, Con PI)[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Human HT29 colorectal carcinoma cells are injected s.c into the flanks of female NCr athymic mice 6-8 weeks of age. Dosing commenced 5 days after transplantation when tumors reach a mean diameter of 5.5 mm. LY 188011 (100 mg/kg i.v.) is dosed in saline on days 0, 7 and 14 and compounds 4 (CCT245737) and 41 (150 mg/kg p.o.) in 10% DMSO 20% PEG 400, 5% Tween 80, 65% water, 24 and 48 h after each dose of LY 188011. Tumors are measured and body weights recorded three times weekly. Animals are culled on an individual basis when tumors reach a predetermined humane endpoint (mean diameter <15 mm)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Osborne JD, et al. Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737). J Med Chem. 2016 Jun 9;59(11):5221-37.
[2]. Walton MI, et al. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eμ-MYC driven B-cell lymphoma.
CCT128930 hydrochloride is a potent and selective inhibitor of AKT (IC50=6 nM). CCT128930 hydrochloride has 28-fold selectivity over the closely related PKA kinase (IC50=168 nM) through the targeting of Met282 of AKT (Met173 of PKA-AKT chimera), as well as 20-fold selectivity over p70S6K (IC50=120 nM). CCT128930 hydrochloride induces cell cycle arrest, DNA damage, and autophagy. Antitumor activity[1][2].
IC50 & Target[1]
Akt2
6 nM (IC50)
PKA
168 nM (IC50)
p70S6K
120 nM (IC50)
Autophagy
Apoptosis
体外研究 (In Vitro)
The GI50 values of CCT128930 hydrochloride for growth inhibition are 6.3 μM for U87MG human glioblastoma cells, 0.35 μM for LNCaP human prostate cancer cells, and 1.9 μM for PC3 human prostate cancer cells, all of which are PTEN-deficient human tumor cell lines[1]. CCT128930 (0.1-60 μM; 1 hour; U87MG human glioblastoma cells) hydrochloride shows an initial induction of AKT phosphorylation at serine 473 up to 20 μM, followed by a decreased in phosphorylation at higher concentrations[1]. CCT128930 hydrochloride inhibits direct substrates of AKT (Ser9 GSK3β, pThr246 PRAS40 and pT24 FOXO1/p32 FOXO3a) at ≥5 μM, and the downstream target, pSer235/236 S6RP at ≥10 μM, with generally constant levels of the respective total proteins and GAPDH[1]. CCT128930 (18.9 μM; U87MG human glioblastoma cells) hydrochloride causes an increase in phosphorylation of pSer473 AKT after 30 minutes, which is sustained for 48 hours. Total AKT protein signal decreases gradually from 8 hours to 48 hours of treatment[1]. CCT128930 (PTEN-null U87MG human glioblastoma cells; over a 24-hour time period) hydrochloride results in an increase in G0/G1 phase cells from 43.6% to 64.8% after 24 hours of treatment[1]. CCT128930 (0-10 μM; 24 hours) hydrochloride increases, but not inhibites, the phosphorylation of Akt in HepG2 and A549 cells. CCT128930 (0-20 μM; 24 hours) hydrochloride inhibits cell proliferation by inducing cell cycle arrest in G1 phase through downregulation of cyclinD1 and Cdc25A, and upregulation of p21, p27 and p53. CCT128930 (20 μM) hydrochloride triggers cell apoptosis with activation of caspase-3, caspase-9, and PARP. CCT128930 (0-20 μM; 24 hours) hydrochloride increases phosphorylation of ERK and JNK in HepG2 cells. CCT128930 (0-20 μM; 24 hours) hydrochloride activates DNA damage response of HepG2 cell characterized by phosphorylation of H2AX, ATM (ataxia-telangiectasia mutated), Chk1 and Chk2[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
CCT128930 (25 or 40 mg/kg; i.p. daily or twice daily for 5 days) hydrochloride shows antitumor activities in U87MG and BT474 human breast cancer xenografts[1]. Summary of the pharmacokinetic parameters of CCT128930 (25 mg/kg) in CrTacNCr-Fox1nu mice[1]
Tissue
Route
T1/2 (h)
Tmax (h)
Cmax (μM)
Vss (L)
Cl (L/h)
AUC0-∞ (µMh)
Bioavailability (%)
Plasma
i.v.
0.95
0.083
6.36
0.25
0.325
4.62
100
Plasma
i.p.
2.33
0.5
1.28
N/A
0.372
1.33
28.8
Tumor
i.p.
3.89
1
8.02
N/A
0.06*
25.8
N/A
Plasma
p.o.
0.57
0.5
0.432
N/A
0.317
0.392
8.5
*Apparent clearance.
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
6-8 weeks old female CrTacNCr-Fox1nu mice[1]
Dosage:
25 mg/kg (U87MG human glioblastoma xenografts) or 40 mg/kg (BT474 human breast cancer xenografts)
Administration:
i.p. daily for 5 days (U87MG human glioblastoma xenografts); i.p. twice daily for 5 days (BT474 human breast cancer xenografts)
Result:
Giving a treated:control (T/C) ratio on day 12 of 48%. There was no weight loss associated with this regime in U87MG human glioblastoma xenografts. Had a profound antitumor effect with complete growth arrest and a T/C ratio of 29% on day 22. This regimen was associated with minimal weight loss, with a nadir of only 94.8% of the initial body weight on day 15 of treatment in BT474 human breast cancer xenografts.
分子量
378.30
Formula
C18H21Cl2N5
CAS 号
2453324-32-6
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
*以上所有助溶剂都可在 Shanghai Jinpan Biotech Co Ltd 网站选购。
参考文献
[1]. Yap TA et al. Preclinical pharmacology, antitumor activity, and development of pharmacodynamic markers for the novel, potent AKT inhibitor CCT128930. Mol Cancer Ther. 2011 Feb;10(2):360-71.
[2]. Wang FZ, et al. CCT128930 induces cell cycle arrest, DNA damage, and autophagy independent of Akt inhibition. Biochimie. 2014;103:118-125.
CCT245232 is a potent inhibitor of heat shock factor 1 (HSF1). HSF1 is the master regulator of the heat shock response, in which multiple genes are induced in response to temperature increase and other stresses. CCT245232 has the potential for the research of proliferative diseases, such as cancer (extracted from patent WO2015049535A1)[1].
分子量
453.49
Formula
C27H23N3O4
CAS 号
1693731-14-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Keith Jones, et al. Fused 1,4-dihydrodioxin derivatives as inhibitors of heat shock transcription factor 1. Patent WO2015049535A1.
CCT251545 is an orally bioavailable and potent inhibitor of WNT signaling with an IC50 of 5 nM in 7dF3 cells[1]. CCT251545 is a selective chemical probe for exploring the role of CDK8 and CDK19 in human disease[2].
IC50 & Target
IC50: 5 nM (WNT, 7dF3 cells)[1]
体外研究 (In Vitro)
CCT251545 potently inhibits WNT pathway activity in COLO205-F1756 clone 4 (an APC -mutant human colorectal cancer cell line engineered to express a modified luciferase-based WNT reporter construct) with an IC50 of 0.035 μM[1]. CCT251545 has weak inhibition of tankyrase enzymes (TNKS1 IC50 > 10 μM, TNKS2 IC50 = 15.0)[1]. CCT251545 is a potent and selective chemical probe for the human mediator complex-associated protein kinases CDK8 and CDK19 with >100-fold selectivity over 291 other kinases[2]. CCT251545 alters WNT pathway-regulated gene expression and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1[2]. CCT251545 also reduces phospho-STAT1SER727 levels in SW620 cells with an IC50 of 9 nM[2]. CCT251545 displays potent cell-based activity[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
CCT251545 (70mg/kg; p.o.; twice daily) causes an inhibition of tumor growth in NCr athymic mice bearing established SW620 human colorectal cancer xenografts[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
6-8 weeks female NCr athymic mice bearing established SW620 xenografts[2]
Dosage:
70mg/kg
Administration:
Oral administration; twice daily; from days 0-7 and days 10-14
Result:
Caused an inhibition of tumor growth with a 70% reduction in final tumor weight relative to control.
分子量
421.92
Formula
C23H24ClN5O
CAS 号
1661839-45-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Mallinger A, et al. Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J Med Chem. 2015 Feb 26;58(4):1717-35.
[2]. Dale T, et al. A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nat Chem Biol. 2015 Dec;11(12):973-980.
CCT251545 is an orally bioavailable and potent inhibitor of WNT signaling with an IC50 of 5 nM in 7dF3 cells[1]. CCT251545 is a selective chemical probe for exploring the role of CDK8 and CDK19 in human disease[2].
IC50 & Target
IC50: 5 nM (WNT, 7dF3 cells)[1]
体外研究 (In Vitro)
CCT251545 potently inhibits WNT pathway activity in COLO205-F1756 clone 4 (an APC -mutant human colorectal cancer cell line engineered to express a modified luciferase-based WNT reporter construct) with an IC50 of 0.035 μM[1]. CCT251545 has weak inhibition of tankyrase enzymes (TNKS1 IC50 > 10 μM, TNKS2 IC50 = 15.0)[1]. CCT251545 is a potent and selective chemical probe for the human mediator complex-associated protein kinases CDK8 and CDK19 with >100-fold selectivity over 291 other kinases[2]. CCT251545 alters WNT pathway-regulated gene expression and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1[2]. CCT251545 also reduces phospho-STAT1SER727 levels in SW620 cells with an IC50 of 9 nM[2]. CCT251545 displays potent cell-based activity[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
CCT251545 (70mg/kg; p.o.; twice daily) causes an inhibition of tumor growth in NCr athymic mice bearing established SW620 human colorectal cancer xenografts[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
6-8 weeks female NCr athymic mice bearing established SW620 xenografts[2]
Dosage:
70mg/kg
Administration:
Oral administration; twice daily; from days 0-7 and days 10-14
Result:
Caused an inhibition of tumor growth with a 70% reduction in final tumor weight relative to control.
分子量
421.92
Formula
C23H24ClN5O
CAS 号
1661839-45-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Mallinger A, et al. Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J Med Chem. 2015 Feb 26;58(4):1717-35.
[2]. Dale T, et al. A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nat Chem Biol. 2015 Dec;11(12):973-980.
CCT196969 is a pan-Raf inhibitor, which inhibits B-Raf, BRafV600E and CRAF with IC50s of 0.1, 0.04, and 0.01 μM, respectively.
IC50 & Target[1]
BRafV600E
0.04 μM (IC50)
Braf
0.1 μM (IC50)
CRAF
0.01 μM (IC50)
LCK
0.02 μM (IC50)
SRC
0.03 μM (IC50)
体外研究 (In Vitro)
CCT196969 is a pan-Raf inhibitor with anti-SRC activity. CCT196969 is an orally available, well-tolerated B-Raf inhibitor that directly inhibits B-RafV600E in cells. CCT196969 inhibits B-Raf at 100 nM and B-RafV600E at 40 nM. It inhibits CRaf at 12 nM, SRC at 26 nM, and LCK at 14 nM. CCT196969 is active against melanoma and colorectal cancer cell lines that are mutant for B-Raf. CCT196969 induces caspase 3 and PARP cleavage, demonstrating that it induces apoptosis[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
CCT196969 is extremely well tolerated and does not produce any significant adverse effects in vivo. It inhibits the growth of NRAS mutant DO4 tumor xenografts in nude mice. CCT196969 inhibits ERK and SRC and induce tumor regression in a PDX from the resistant tumor without causing body weight loss in the mice[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
513.52
Formula
C27H24FN7O3
CAS 号
1163719-56-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Girotti MR, et al. Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer Cell. 2015 Jan 12;27(1):85-96.
Cell Assay [1]
Cultured cells are seeded into 96-well plates (2,000 cells per well). At 24 hr later, serial dilutions of the B-Raf inhibitors PLX4720 and SB590885, the MEK inhibitor PD184352, or compounds CCT241161 and CCT196969 are added. Cells are incubated for a further 72 hr, and viability is measured by CellTiter-Glo assays. Relative survival in the presence of drugs is normalized to the untreated controls after background subtraction[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice: Tumors are established in female nude mice. Treatment is by oral gavage daily with vehicle (5% DMSO, 95% water), 90 mg/kg PLX4720, 20 mg/kg CCT196969, or 20 mg/kg CCT241161. All the inhibitors are administered 7 days/week, with no weekend break. Tumor size is determined by caliper measurements of tumor length, width, and depth; volume is calculated as volume = 0.5236×length×width×depth (in millimeters)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Girotti MR, et al. Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer Cell. 2015 Jan 12;27(1):85-96.
CCT129202 is an aurora kinase inhibitor with IC50s of 42, 198, and 227 nM for aurora A, B and C, respectively.
IC50 & Target[1]
Aurora A
42 nM (IC50)
Aurora B
198 nM (IC50)
Aurora C
227 nM (IC50)
体外研究 (In Vitro)
CCT129202 causes the accumulation of human tumor cells with z4N DNA content, leading to apoptosis. CCT129202 is found to induce apoptosis with GI50 values that ranges between 0.08 and 1.7 μM. CCT120202-treated human tumor cells shows a delay in mitosis, abrogation of nocodazole-induced mitotic arrest, and spindle defects. CCT129202 Causes p21Up-regulation, Rb Hypophosphorylation, and H2F-DependentTK1Down-regulation[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Growth of HCT116 xenografts in nude mice is inhibited after i.p. administration of CCT129202. p21, the cyclin-dependent kinase inhibitor, is induced by CCT129202. Up-regulation of p21 by CCT129202 in HCT116 cells led to Rb hypophosphorylation and E2F inhibition, contributing to a decrease in thymidine kinase 1 transcription[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
497.02
Formula
C23H25ClN8OS
CAS 号
942947-93-5
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Chan F, et al. Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3147-57.
Cell Assay [1]
The effects of CCT129202 on cell proliferation are analyzed with the MTT assay. Cells are plated in 96-well plates at 2,500 per well and are treated with a range of 0 to 50 μM of CCT129202 for 72 h. The absorbance is measured at 570 nm[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice: For efficacy studies, human HCT116 colon carcinoma xenografts are established in female mice. CCT129202 is dissolved in DMSO and injected i.p in vehicle, which comprises 10% DMSO, 5% Tween 20, and 85% sterile saline at 0.1 mL/10 g body weight. Dosing with CCT129202 commenced when tumors are well established (f5 mm mean diameter); control animals receive an equivalent volume of vehicle. Mouse body weights and condition are monitored throughout the study. Tumors are measured thrice weekly[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Chan F, et al. Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3147-57.
CCT241533 is a potent and selective ATP competitive inhibitor of CHK2 with an IC50 of 3 nM and Ki of 1.16 nM[1].
IC50 & Target[1]
Chk2
3 nM (IC50)
Chk1
245 nM (IC50)
Chk2
1.16 nM (Ki)
体外研究 (In Vitro)
CCT241533 hydrochloride inhibits CHK2 with an IC50 of 3 nM and shows minimal cross reactivity against a panel of kinases at 1 μM. X-ray crystallography confirms that CCT241533 binds to CHK2 in the ATP pocket. CCT241533 blocks CHK2 activity in human tumor cell lines in response to DNA damage, as demonstrated by inhibition of CHK2 autophosphorylation at S516, band-shift mobility changes and HDMX degradation. CCT241533 does not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, CCT241533 significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal is seen with a PARP inhibitor alone and this activation is abolished by CCT241533. The cytotoxicity of CCT241533 in HT-29, HeLa and MCF-7, measured as the growth inhibitory IC50(GI50) by SRB assay, is 1.7, 2.2 and 5.1 μM, respectively[1]. CCT241533 hydrochloride is a potent CHK2 inhibitor (IC50=3 nM), with selectivity (63-fold) over CHK1(IC50=190 nM) and low hERG inhibition (IC50=22 μM)[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
442.48
Formula
C23H27FN4O4
CAS 号
1262849-73-9
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
[2]. Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.
Cell Assay [1]
HT-29, HeLa and MCF-7 cells are exposed to a fixed concentration (GI50) of CCT241533 in combination with increasing concentrations of either PARP inhibitor or cytotoxic drug in a 96 hour SRB assay or 7-10 day colony forming assay. The ability of CCT241533 to enhance cell killing is expressed as a potentiation index (PI) which is the ratio of GI50 for the genotoxic or PARP inhibitor alone: GI50 for the genotoxic or PARP inhibitor in combination with a CHK2 inhibitor. Thus PI>1 indicates potentiation and PI<1 indicates protection[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
[2]. Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.
CCT251455 is a potent and selective mitotic kinase monopolar spindle 1 (MPS1) inhibitor with an IC50 of 3 nM.
IC50 & Target
IC50: 3 nM (MPS1)[1]
体外研究 (In Vitro)
CCT251455 is a highly potent inhibitor of MPS1 that demonstrates high selectivity versus kinases tested in a broad kinome profiling panel. CCT251455 inhibits P-MPS1 with an IC50 of 0.04 μM in cell-based assay and has a GI50 of 0.16 μM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
CCT251455 demonstrates a good oral pharmacokinetic profile in mouse and rat as well as inhibition of MPS1 activity in vivo following oral administration[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
503.98
Formula
C26H26ClN7O2
CAS 号
1400284-80-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Naud S, et al. Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1). J Med Chem. 2013 Dec 27;56(24):10045-65.
Cell Assay [1]
HCT116 cells are treated with 0-20 μM CCT251455 for 72 h. Cell viability is measured using the MTT assay[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1]
[1]Human HCT116 colon carcinoma cells are sc injected bilaterally in the flanks of female CrTac:NCr-Fox1(nu) athymic mice. Once tumors reach a mean diameter of 8 mm (day 15), mice are dosed twice at a 12 h intervals with 50, 75, or 100 mg/kg of CCT251455 in 10% (v/v) DMSO and 5% (v/v) Tween 20 in saline. Mice are culled (n=3 per group) at 2, 10, and 72 h after the second dose. Tumors are snap-frozen and stored at -80 °C until analysis[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Naud S, et al. Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1). J Med Chem. 2013 Dec 27;56(24):10045-65.
CCT241533 dihydrochloride is a potent and selective ATP competitive inhibitor of CHK2 with an IC50 of 3 nM and Ki of 1.16 nM[1].
IC50 & Target
Chk2
3 nM (IC50)
Chk1
245 nM (IC50)
Chk2
1.16 nM (Ki)
体外研究 (In Vitro)
CCT241533 inhibits CHK2 with an IC50 of 3 nM and shows minimal cross reactivity against a panel of kinases at 1 μM. X-ray crystallography confirms that CCT241533 binds to CHK2 in the ATP pocket. CCT241533 blocks CHK2 activity in human tumor cell lines in response to DNA damage, as demonstrated by inhibition of CHK2 autophosphorylation at S516, band-shift mobility changes and HDMX degradation. CCT241533 does not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, CCT241533 significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal is seen with a PARP inhibitor alone and this activation is abolished by CCT241533. The cytotoxicity of CCT241533 in HT-29, HeLa and MCF-7, measured as the growth inhibitory IC50(GI50) by SRB assay, is 1.7, 2.2 and 5.1 μM, respectively[1]. CCT241533 hydrochloride is a potent CHK2 inhibitor (IC50=3 nM), with selectivity (63-fold) over CHK1(IC50=190 nM) and low hERG inhibition (IC50=22 μM)[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
515.41
Formula
C23H29Cl2FN4O4
CAS 号
1962925-28-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
[2]. Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.
CCT241533 dihydrochloride is a potent and selective ATP competitive inhibitor of CHK2 with an IC50 of 3 nM and Ki of 1.16 nM[1].
IC50 & Target
Chk2
3 nM (IC50)
Chk1
245 nM (IC50)
Chk2
1.16 nM (Ki)
体外研究 (In Vitro)
CCT241533 inhibits CHK2 with an IC50 of 3 nM and shows minimal cross reactivity against a panel of kinases at 1 μM. X-ray crystallography confirms that CCT241533 binds to CHK2 in the ATP pocket. CCT241533 blocks CHK2 activity in human tumor cell lines in response to DNA damage, as demonstrated by inhibition of CHK2 autophosphorylation at S516, band-shift mobility changes and HDMX degradation. CCT241533 does not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, CCT241533 significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal is seen with a PARP inhibitor alone and this activation is abolished by CCT241533. The cytotoxicity of CCT241533 in HT-29, HeLa and MCF-7, measured as the growth inhibitory IC50(GI50) by SRB assay, is 1.7, 2.2 and 5.1 μM, respectively[1]. CCT241533 hydrochloride is a potent CHK2 inhibitor (IC50=3 nM), with selectivity (63-fold) over CHK1(IC50=190 nM) and low hERG inhibition (IC50=22 μM)[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
515.41
Formula
C23H29Cl2FN4O4
CAS 号
1962925-28-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
[2]. Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.
CCT241533 dihydrochloride is a potent and selective ATP competitive inhibitor of CHK2 with an IC50 of 3 nM and Ki of 1.16 nM[1].
IC50 & Target
Chk2
3 nM (IC50)
Chk1
245 nM (IC50)
Chk2
1.16 nM (Ki)
体外研究 (In Vitro)
CCT241533 inhibits CHK2 with an IC50 of 3 nM and shows minimal cross reactivity against a panel of kinases at 1 μM. X-ray crystallography confirms that CCT241533 binds to CHK2 in the ATP pocket. CCT241533 blocks CHK2 activity in human tumor cell lines in response to DNA damage, as demonstrated by inhibition of CHK2 autophosphorylation at S516, band-shift mobility changes and HDMX degradation. CCT241533 does not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, CCT241533 significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal is seen with a PARP inhibitor alone and this activation is abolished by CCT241533. The cytotoxicity of CCT241533 in HT-29, HeLa and MCF-7, measured as the growth inhibitory IC50(GI50) by SRB assay, is 1.7, 2.2 and 5.1 μM, respectively[1]. CCT241533 hydrochloride is a potent CHK2 inhibitor (IC50=3 nM), with selectivity (63-fold) over CHK1(IC50=190 nM) and low hERG inhibition (IC50=22 μM)[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
515.41
Formula
C23H29Cl2FN4O4
CAS 号
1962925-28-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
[2]. Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.
CCT018159, a 3,4-diaryl pyrazoleresorcinol, is a ATP-competitive HSP90 ATPase activity inhibitor with IC50s of 3.2 and 6.6 µM for human Hsp90β and yeast Hsp90, respectively. CCT018159 caused cell cytostasis associated with a G1 arrest and induces apoptosis. CCT018159 inhibits key endothelial and tumor cell functions implicated in invasion and angiogenesis[1].
IC50 & Target[1]
human Hsp90β
3.2 μM (IC50)
yeast Hsp90
6.6 μM (IC50)
分子量
352.38
Formula
C20H20N2O4
CAS 号
171009-07-7
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Swee Y Sharp, et al. In vitro biological characterization of a novel, synthetic diaryl pyrazole resorcinol class of heat shock protein 90 inhibitors. Cancer Res. 2007 Mar 1;67(5):2206-16.
CCT018159, a 3,4-diaryl pyrazoleresorcinol, is a ATP-competitive HSP90 ATPase activity inhibitor with IC50s of 3.2 and 6.6 µM for human Hsp90β and yeast Hsp90, respectively. CCT018159 caused cell cytostasis associated with a G1 arrest and induces apoptosis. CCT018159 inhibits key endothelial and tumor cell functions implicated in invasion and angiogenesis[1].
IC50 & Target[1]
human Hsp90β
3.2 μM (IC50)
yeast Hsp90
6.6 μM (IC50)
分子量
352.38
Formula
C20H20N2O4
CAS 号
171009-07-7
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Swee Y Sharp, et al. In vitro biological characterization of a novel, synthetic diaryl pyrazole resorcinol class of heat shock protein 90 inhibitors. Cancer Res. 2007 Mar 1;67(5):2206-16.
CCT018159, a 3,4-diaryl pyrazoleresorcinol, is a ATP-competitive HSP90 ATPase activity inhibitor with IC50s of 3.2 and 6.6 µM for human Hsp90β and yeast Hsp90, respectively. CCT018159 caused cell cytostasis associated with a G1 arrest and induces apoptosis. CCT018159 inhibits key endothelial and tumor cell functions implicated in invasion and angiogenesis[1].
IC50 & Target[1]
human Hsp90β
3.2 μM (IC50)
yeast Hsp90
6.6 μM (IC50)
分子量
352.38
Formula
C20H20N2O4
CAS 号
171009-07-7
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Swee Y Sharp, et al. In vitro biological characterization of a novel, synthetic diaryl pyrazole resorcinol class of heat shock protein 90 inhibitors. Cancer Res. 2007 Mar 1;67(5):2206-16.
CCT 031374 hydrobromid is a potent inhibitor of β-catenin/transcription factor (TCF) complex signaling. CCT031374 inhibits TCF-dependent transcription of genes of Wnt signaling pathway. CCT 031374 has antitumor activity[1].
分子量
434.33
Formula
C23H20BrN3O
CAS 号
1219184-91-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Ewan K, et al. A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription. Cancer Res. 2010 Jul 15;70(14):5963-73.
CCT241533 hydrochloride is a potent and selective CHK2 inhibitor with an IC50 of 3 nM and a Ki of 1.16 nM[1].
IC50 & Target[1]
Chk2
3 nM (IC50)
Chk1
245 nM (IC50)
Chk2
1.16 nM (Ki)
体外研究 (In Vitro)
CCT241533 hydrochloride inhibits CHK2 with an IC50 of 3 nM and shows minimal cross reactivity against a panel of kinases at 1 μM. X-ray crystallography confirms that CCT241533 binds to CHK2 in the ATP pocket. CCT241533 blocks CHK2 activity in human tumor cell lines in response to DNA damage, as demonstrated by inhibition of CHK2 autophosphorylation at S516, band-shift mobility changes and HDMX degradation. CCT241533 does not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, CCT241533 significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal is seen with a PARP inhibitor alone and this activation is abolished by CCT241533. The cytotoxicity of CCT241533 in HT-29, HeLa and MCF-7, measured as the growth inhibitory IC50(GI50) by SRB assay, is 1.7, 2.2 and 5.1 μM, respectively[1]. CCT241533 hydrochloride is a potent CHK2 inhibitor (IC50=3 nM), with selectivity (63-fold) over CHK1(IC50=190 nM) and low hERG inhibition (IC50=22 μM)[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
478.94
Formula
C23H28ClFN4O4
CAS 号
1431697-96-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
[2]. Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.
Cell Assay [1]
HT-29, HeLa and MCF-7 cells are exposed to a fixed concentration (GI50) of CCT241533 in combination with increasing concentrations of either PARP inhibitor or cytotoxic drug in a 96 hour SRB assay or 7-10 day colony forming assay. The ability of CCT241533 to enhance cell killing is expressed as a potentiation index (PI) which is the ratio of GI50 for the genotoxic or PARP inhibitor alone: GI50 for the genotoxic or PARP inhibitor in combination with a CHK2 inhibitor. Thus PI>1 indicates potentiation and PI<1 indicates protection[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
[2]. Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.
CCT020312 is a selective EIF2AK3/PERK activator. CCT020312 elicits EIF2A phosphorylation in cells.
IC50 & Target
EIF2AK3/PERK[1][2].
体外研究 (In Vitro)
Treatment of HT29 cells with CCT020312 for 24 hours reveals a concentration-dependent loss of P-S608-pRB signal, with a linear response between 1.8 and 6.1 μM[1]. CCT020312 treatment effectively inhibits cell proliferation (as measured at 96 hours) even if treatment is for 2 hours only with subsequent compound washout, indicating that CCT020312 is capable of eliciting durable rather than transient cytostasis[1]. Treatment of HT29 cells with 10 μM CCT020312 for 24 hours reduces the amount of the G1/S cyclins D1, D2, E and A as well as the CDK catalytic subunit CDK2 and increased the level of the CDK inhibitor p27KIP1 present in such cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Treatment of 15-week-old wildtype mice with the PERK activator CCT020312 (1-5 mg/kg; i.p.; once daily for 3 days) leads to increased levels of phosphorylated PERK and NRF2 in brain homogenates[2]. P301S transgenic mice treated with CCT020312 (2 mg/kg; i.p.; once daily for 6 weeks) performes significantly better in Morris water maze[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
9-week-old P301S tau transgenic mice[2]
Dosage:
2 mg/kg
Administration:
Intraperitoneal injection; once daily for 6 weeks
Result:
P301S transgenic mice treated with CCT020312 performed significantly better in Morris water maze.
分子量
650.40
Formula
C31H30Br2N4O2
CAS 号
324759-76-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Stockwell SR, et al.Mechanism-based screen for G1/S checkpoint activators identifies a selective activator of EIF2AK3/PERK signalling. PLoS One. 2012;7(1):e28568.
[2]. Bruch J, et al. PERK activation mitigates tau pathology in vitro and in vivo. EMBO Mol Med. 2017 Mar;9(3):371-384.
