CCT367766 is a potent and the third generation heterobifunctional and Cereblon-based pirin targeting protein degradation probe (PDP, or PROTAC), depletes pirin protein expression at low concentration. CCT367766 exhibits a moderate affinity for the CRBN-DDB1 complex with an IC50 value of 490 nM. CCT367766 reveals a good affinity for the recombinant pirin and CRBN with Kd values of 55 nM and 120 nM, respectively. CCT367766 provides a potential chemical tool to study a largely unexplored protein[1].
IC50 & Target[1]
CRBN-DDB1
490 nM (IC50)
体外研究 (In Vitro)
CCT367766 (50-1500 nM; 24 hours) demonstates the depletion of pirin protein as a the time-dependent hook-effect in SK-OV-3 human ovarian cancer cells[1]. CCT367766 (0.5-50 nM; 2 hours) demonstrates the concentration-dependent depletion of pirin protein after 2 h exposure in SK-OV-3 cells[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
SK-OV-3 human ovarian cancer cells
Concentration:
50, 150, 250, 500 and 1500 nM
Incubation Time:
2 hours, 4 hours, 24 hours
Result:
Decreased pirin protein expression.
Western Blot Analysis[1]
Cell Line:
SK-OV-3 human ovarian cancer cells
Concentration:
0.5, 1, 2.5, 5, 7.5, 10, 25, and 50 nM
Incubation Time:
2 hours
Result:
Completely degraded pirin just at 50 nM treatment.
分子量
946.40
Formula
C49H48ClN7O11
CAS 号
2229856-58-8
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]. Chessum NEA, et al. Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766).J Med Chem. 2018 Feb 8;61(3):918-933.
CCT365623 hydrochloride is an orally active lysyl oxidase (LOX) inhibitor, with an IC50 of 0.89 μM. CCT365623 hydrochloride suppresses EGFR (pY1068) and AKT phosphorylation driven by EGF. CCT365623 hydrochloride is extremely well tolerated, and has good pharmacokinetic properties[1].
IC50 & Target
IC50: 0.89 μM (LOX)[1].
体外研究 (In Vitro)
CCT365623 inhibits LOX at ~5 μM in the biosensor system[1]. CCT365623 (0-40 μM) concentration-dependently decreases the protein levels of surface EGFR[1]. CCT365623 (5 μM) decreases the protein levels of pY1068 EGFR, pAKT and MATN2, and increases the protein levels of pSMAD2[1]. CCT365623 disrupts HTRA1 multimerization, activates TGFβ1 signalling, suppresses MATN2 expression, suppresses EGFR surface retention, and suppresses EGFR signalling[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.
Western Blot Analysis[1]
Cell Line:
MDA-MB-231 cells.
Concentration:
0-40 μM.
Incubation Time:
24 hours
Result:
Significantly decreased the protein levels of surface EGFR, pY1068 EGFR, pAKT and MATN2. Increased the protein levels of pSMAD2.
体内研究 (In Vivo)
CCT365623 displays good stability in mouse liver microsomes and does not inhibit the cardiac potassium channel hERG[1]. CCT365623 (70 mg/kg, oral gavage per day) significantly delays the development of the primary tumors and also suppresses metastatic lung burden in the animals. CCT365623 disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumor cell[1]. CCT365623 exhibits a T1/2PO of 0.6 h and F% (oral bioavailability) of 45%[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:
Mouse model of spontaneous breast cancer that metastasizes to the lungs (70 days old)[1].
Dosage:
70 mg/kg.
Administration:
Oral gavage per day for about 3 weeks.
Result:
Significantly reduced MATN2 protein levels in both the primary and metastatic lung tumors and this is accompanied by the loss of EGFR from the plasma membranes of the cells in both the primary and metastatic tumors.
分子量
443.99
Formula
C18H18ClNO4S3
CAS 号
2126136-98-7
运输条件
Room temperature in continental US; may vary elsewhere.
CCT007093 is an effective protein phosphatase 1D (PPM1D Wip1) inhibitor. Wip1 inhibition can activate the mTORC1 pathway and enhance hepatocyte proliferation after hepatectomy[1][2].
体外研究 (In Vitro)
CCT007093 (25 or 50 µM, 8 h) significantly increases the phosphorylation levels of mTOR at Ser2448, Ser2481 and Ser2159, and the phosphorylation levels of p70S6K (Thr389) and S6 (Ser235/236) are also up-regulated in transfected HEK293T cell line[1]. CCT007093 shows specificity for MCF-7 cells, reducing viability by 40% after 2 days with no observable effect on the growth of HeLa cells[2]. CCT007093 induces P38 phosphorylation at 4 h post exposure in MCF-7 cells (sensitive to PPM1D inhibition), and does not induce P38 phosphorylation in HeLa cells (relatively resistant to PPM1D inhibition)[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.
Western Blot Analysis[1]
Cell Line:
HEK293T cell line.
Concentration:
25 or 50 µM.
Incubation Time:
8 h.
Result:
The phosphorylation levels of mTOR at Ser2448, Ser2481 and Ser2159 were all significantly increased[1]. The phosphorylation levels of p70S6K (Thr389) and S6 (Ser235/236) were also up-regulated[1].
体内研究 (In Vivo)
CCT007093 (6.4 mg/kg) enhances liver regeneration and increases the survival rate of mice following major hepatectomy[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:
Wild-type mice[1].
Dosage:
3.2 and 6.4 mg/kg.
Administration:
Injected intraperitoneally 4 times (mice were sacrificed at 36 h post-PH).
Result:
Significantly improved survival in mice following major hepatectomy (80% hepatectomy). The level of PCNA was also significantly increased in the liver of CCT007093-treated mice at 36h, 48h and 72h post-PH.
分子量
272.39
Formula
C15H12OS2
CAS 号
176957-55-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Lingling Zhang, et al. Inhibition of wild-type p53-induced phosphatase 1 promotes liver regeneration in mice by direct activation of mammalian target of rapamycin. Hepatology. 2015 Jun;61(6):2030-41.
[2]. S Rayter, et al. A chemical inhibitor of PPM1D that selectively kills cells overexpressing PPM1D. Oncogene. 2008 Feb 14;27(8):1036-44.
CCT-251921 is a potent, selective, and orally bioavailable CDK8 inhibitor with an IC50 of 2.3 nM.
IC50 & Target[1]
CDK8
2.3 nM (IC50)
CDK19
2.6 nM (IC50)
体外研究 (In Vitro)
CCT-251921 has acceptable aqueous solubility and demonstrates minimal activity when tested in a panel of 55 receptors, ion channels, and enzymes at 1 μM and in a panel of 279 kinases; weak inhibition of CYPs is observed. CCT-251921 demonstrates potent inhibition of reporter-based readouts measuring basal WNT pathway activity in human cancer cell lines that have constitutively activated WNT pathway signaling: LS174T (β-catenin mutant), SW480 and Colo205 (APC mutant) or PA-1 human teratocarcinoma cells that are WNT ligand dependent[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)
CCT-251921 shows improved oral pharmacokinetics and pharmaceutical properties in order to facilitate further evaluation of CDK8/19 pharmacology and progression into preclinical efficacy and safety studies. In APC-mutant SW620 human colorectal carcinoma xenograft model, CCT-251921 treatment reduces mice tumor weight (54.2%) at day 15. The inhibition of STAT1SER727 phosphorylation is maintained for more than 6 h after the last dose[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
410.90
Formula
C21H23ClN6O
CAS 号
1607837-31-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Mallinger A, et al. Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. J Med Chem. 2016 Feb 11;59(3):1078-101.
Cell Assay [1]
7dF3 cells are treated with CCT-251921 ranging in final concentration from 90 μM to 0.3 nM. After 2 h of further incubation, β-oestradiol is added to a final concentration of 10 μM. The cells are incubated and then 25 μL of luciferase reagent is added and mixed. After leaving the plate for 60 min at room temperature, luminescence is read on a plate luminescence reader[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: Animals are dosed orally by gavage every 24 h at 0.1 mL per 10 g body weight. Tumors are measured three times weekly by Vernier calipers and body weights recorded. At the end of the study, animals are culled at intervals: 3 control and 3 treated at 1, 2, 6, and 24 h after the final dose. Heparinized blood is collected by cardiac puncture, spun, and plasma snap frozen for analysis of compound exposure. Tumors are excised, weighed and samples snap frozen for compound quantification and PD analyses. The 30 mg/kg q.d. schedule is well tolerated with no significant body weight loss. Tumor growth is significantly inhibited[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]. Mallinger A, et al. Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. J Med Chem. 2016 Feb 11;59(3):1078-101.
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.
