Ginsenoside Rg6 inhibits TNF-α-induced NF-κB transcriptional activity with an IC50 of 29.34 μM in HepG2 cells. Ginsenoside Rg6 also exhibits apoptosis-inducing effect.
IC50 & Target[1][2]
NF-κB
25.12 μM (IC50, in SK-Hep1 cell)
NF-κB
29.34 μM (IC50, in HepG2 cell)
Apoptosis
体外研究 (In Vitro)
Ginsenoside Rg6 inhibits TNF-α-induced NF-κB transcriptional activity with an IC50 of 25.12±1.04 μM in SK-Hep1 cells, consistent with the data from HepG2 cells[1]. Ginsenoside Rg6 exhibits obvious anti-proliferative and apoptosis-inducing effects when it is applied to JK cells in vitro. Ginsenoside Rg6 blocks S arrest in the cell cycle. CCK-8 method shows that after Ginsenoside Rg6 is used, several groups with different concentrations obviously inhibits JK cell proliferation in human lymphocytoma, with evident dose dependency. Based on IC50, the median inhibitory concentration of Ginsenoside Rg6 is 83.08 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
767.00
Formula
C42H70O12
CAS 号
147419-93-0
中文名称
人参皂苷 Rg6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Cho K, et al. Inhibition of TNF-α-Mediated NF-κB Transcriptional Activity by Dammarane-Type Ginsenosidesfrom Steamed Flower Buds of Panax ginseng in HepG2 and SK-Hep1 Cells. Biomol Ther (Seoul). 2014 Jan;22(1):55-61.
[2]. Chen B, et al. Apoptosis-inducing effect of ginsenoside Rg6 on human lymphocytoma JK cells. Molecules. 2013 Jul 9;18(7):8109-19.
Cell Assay [1]
HepG2 and SK-Hep1 cells are maintained in Dulbecco’s modified Eagle’s medium containing 10% heat-inactivated fetal bovine serum, 100 units/mL Penicillin, and 10 μg/mL Streptomycin, at 37°C and 5% CO2. Cell-Counting Kit (CCK)-8is used to analyze the effect of compounds (e.g., Ginsenoside Rg6; 0.01, 0.1, 1 and 10 μM) on cell toxicity. Cells are cultured overnight in 96-well plate (~1×104 cells/well). Cell toxicity is assessed after the addition of compounds on dose-dependent manner. After 24 h of treatment, 10 μL of the CCK-8 solution is added to triplicate wells, and incubated for 1 h. Absorbance is measured at 450 nm to determine viable cell numbers in wells[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]. Cho K, et al. Inhibition of TNF-α-Mediated NF-κB Transcriptional Activity by Dammarane-Type Ginsenosidesfrom Steamed Flower Buds of Panax ginseng in HepG2 and SK-Hep1 Cells. Biomol Ther (Seoul). 2014 Jan;22(1):55-61.
[2]. Chen B, et al. Apoptosis-inducing effect of ginsenoside Rg6 on human lymphocytoma JK cells. Molecules. 2013 Jul 9;18(7):8109-19.
RG13022 is a tyrosine kinase inhibitor; inhibits the autophosphorylation reaction of the EGF receptor with an IC50 of 4 μM.
IC50 & Target
IC50: 4 μM (EGF receptor autophosphorylation)[1]
体外研究 (In Vitro)
RG13022 suppresses EGF-stimulated cancer cell proliferation. In a cell-free reaction RG13022 inhibits the autophosphorylation reaction of the EGF receptor in immunoprecipitates with an IC50 of 4 μM. RG13022 inhibits colony formation and DNA synthesis by HER 14 cells, which were stimulated by 50 ng/mL EGF, in a dose-dependent manner. The IC50s are 1 and 3 μM for HER 14 colony formation and DNA synthesis, respectively[1]. RG-13022 inhibits not only EGF-induced growth but also growth stimulated by insulin, insulin-like growth factor I, insulin-like growth factor II, or transforming growth factor alpha. RG-13022 also totally blocks estrogen-stimulated phosphorylation of the EGF receptor, as well as estrogen-induced cell proliferation, suggesting that functioning TK pathways are required for estrogen action[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)
RG13022 suppresses tumor growth in nude mice. RG13022 also increases the life span of these tumor-bearing nude 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
266.29
Formula
C16H14N2O2
CAS 号
136831-48-6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Yoneda T, et al. The antiproliferative effects of tyrosine kinase inhibitors tyrphostins on a human squamous cell carcinoma in vitro and in nude mice. Cancer Res. 1991 Aug 15;51(16):4430-5.
[2]. Reddy KB, et al. Inhibition of breast cancer cell growth in vitro by a tyrosine kinase inhibitor. Cancer Res. 1992 Jul 1;52(13):3636-41.
Cell Assay [1]
40 mM stock solutions of RG13022 is made in 100% DMSO and diluted with the culture medium before addition to the cells. MH-85 cells and HER 14 cells are plated in culture medium in the presence or absence of increasing concentrations of RG-13022 or RG-14620 for 10 days. At the end of culture, the cells are fixed with 4% (v/v) formaldehyde and stained with hematoxylin. Numbers of colonies including more than 20 cells in each well are counted under the microscope[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: MH-85 tumors 5 mm in diameter are inoculated s.c. into the right dorsal portion of 4- to 6-week-old male BALB/c nu/nu mice. RG-13022 or RG-14620 in 0.1 ml 100% DMSO is injected i.p. twice a day from 1day after MH-85 tumor inoculation. Control animals are given the same vehicle. Tumor sizes are measured once a week under anesthesia with nembutal (0.05 mg/g body weight, i.p.) and calculated[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]. Yoneda T, et al. The antiproliferative effects of tyrosine kinase inhibitors tyrphostins on a human squamous cell carcinoma in vitro and in nude mice. Cancer Res. 1991 Aug 15;51(16):4430-5.
[2]. Reddy KB, et al. Inhibition of breast cancer cell growth in vitro by a tyrosine kinase inhibitor. Cancer Res. 1992 Jul 1;52(13):3636-41.
GDC-0425 (RG-7602) is an orally available, highly selective small molecule ChK1 inhibitor. GDC-0425 can be used for the research of various malignancies[1][2].
IC50 & Target[1]
Chk1
体外研究 (In Vitro)
MEK inhibition either by pharmacologic inhibitors or RNAi-mediated gene silencing significantly protected cells from reduced viability upon GDC-0425 treatment[3]. GDC-0425 (3 μM; 24 hours) treatment results the hyperphosphorylation of Chk1[3].
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.
Cell Viability Assay[3]
Cell Line:
Chk1-positive breast cancer cell lines
Concentration:
0.001, 0.01, 0.1, 1, 10 mM
Incubation Time:
72 hours
Result:
Reduced cell proliferation.
Cell Viability Assay[3]
Cell Line:
U-2 OS cells
Concentration:
3 μM
Incubation Time:
24 hours
Result:
Led to hyperphosphorylation of Chk1.
体内研究 (In Vivo)
GDC-0425 exhibits partial suppression of tumor growth. The Gemcitabine/GDC-0425 combination results in significant tumor regression in all tested models[3].
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:
NCr nude mice bearing xenografts of both osteosarcoma and triple-negative breast cancer models (143B PML BK TK, HCC1806, and HCC70 cell lines)[3]
Dosage:
For the 4-arm study, mice were treated with vehicle, Gemcitabine 120 mg/kg, GDC-0425 75 mg/kg alone, or Gemcitabine and GDC-0425 combination for 15 days. For 6-arm studies of HCC1806 and HCC70 models, mice were treated with vehicle, Gemcitabine 120 mg/kg, GDC-0425 50 mg/kg, GDC-0425 75 mg/kg alone, or Gemcitabine and GDC-0425 combination.
Administration:
Orally administrated at 24, 48, and 72 hours after gemcitabine administration by intraperitoneal injection.
Result:
Exhibited partial suppression of tumor growth upon treatment with either Gemcitabine or GDC-0425 alone. Notably, the Gemcitabine/GDC-0425 combination resulted in significant tumor regression in all tested models.
分子量
321.38
Formula
C18H19N5O
CAS 号
1200129-48-1
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:
H2O : 25 mg/mL (77.79 mM; ultrasonic and adjust pH to 3 with HCl)
[1]. Xiao Ding, et al. A supported liquid extraction LC-MS/MS method for determination of concentrations of GDC-0425, a small molecule Checkpoint kinase 1 inhibitor, in human plasma. Biomed Chromatogr. 2016 Dec;30(12):1984-1991.
[2]. Jeffrey R Infante, et al. Phase I Study of GDC-0425, a Checkpoint Kinase 1 Inhibitor, in Combination with Gemcitabine in Patients with Refractory Solid Tumors. Clin Cancer Res. 2017 May 15;23(10):2423-2432.
[3]. Ho-June Lee, et al. Ras-MEK Signaling Mediates a Critical Chk1-Dependent DNA Damage Response in Cancer Cells. Mol Cancer Ther. 2017 Apr;16(4):694-704.
RG-12915 is a selective 5-HT3 antagonist, with IC50 value of 0.16 nM.
IC50 & Target
5-HT3 Receptor
0.16 nM (IC50)
体外研究 (In Vitro)
RG 12915 is a potent and selective displacer of binding of 5-hydroxytryptamine (5-HT3) binding sites (IC50 value = 0.16 nM), whereas failing to displace binding of ligands for the alpha-1, alpha-2 and beta adrenergic, 5-HT1 or 5-HT2 or cholinergic-muscarinic sites with IC50 values less than 1 μM.
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)
RG 12915 has a lower ED50 value (0.004 mg/kg) for attenuating cisplatin-induced emetic episodes in the ferret. RG 12915 (1 mg/kg, p.o.) is highly protective against cisplatin-induced emesis in the dog. RG 12915 has no significant gastroprokinetic activity in the same species[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
360.88
Formula
C20H25ClN2O2
CAS 号
136174-04-4
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]. Fitzpatrick LR, et al. RG 12915: a potent 5-hydroxytryptamine-3 antagonist that is an orally effective inhibitor of cytotoxic drug-induced emesis in the ferret and dog. J Pharmacol Exp Ther. 1990 Aug;254(2):450-5.
RG-12915 is a selective 5-HT3 antagonist, with IC50 value of 0.16 nM.
IC50 & Target
5-HT3 Receptor
0.16 nM (IC50)
体外研究 (In Vitro)
RG 12915 is a potent and selective displacer of binding of 5-hydroxytryptamine (5-HT3) binding sites (IC50 value = 0.16 nM), whereas failing to displace binding of ligands for the alpha-1, alpha-2 and beta adrenergic, 5-HT1 or 5-HT2 or cholinergic-muscarinic sites with IC50 values less than 1 μM.
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)
RG 12915 has a lower ED50 value (0.004 mg/kg) for attenuating cisplatin-induced emetic episodes in the ferret. RG 12915 (1 mg/kg, p.o.) is highly protective against cisplatin-induced emesis in the dog. RG 12915 has no significant gastroprokinetic activity in the same species[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
360.88
Formula
C20H25ClN2O2
CAS 号
136174-04-4
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]. Fitzpatrick LR, et al. RG 12915: a potent 5-hydroxytryptamine-3 antagonist that is an orally effective inhibitor of cytotoxic drug-induced emesis in the ferret and dog. J Pharmacol Exp Ther. 1990 Aug;254(2):450-5.
RG-12915 is a selective 5-HT3 antagonist, with IC50 value of 0.16 nM.
IC50 & Target
5-HT3 Receptor
0.16 nM (IC50)
体外研究 (In Vitro)
RG 12915 is a potent and selective displacer of binding of 5-hydroxytryptamine (5-HT3) binding sites (IC50 value = 0.16 nM), whereas failing to displace binding of ligands for the alpha-1, alpha-2 and beta adrenergic, 5-HT1 or 5-HT2 or cholinergic-muscarinic sites with IC50 values less than 1 μM.
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)
RG 12915 has a lower ED50 value (0.004 mg/kg) for attenuating cisplatin-induced emetic episodes in the ferret. RG 12915 (1 mg/kg, p.o.) is highly protective against cisplatin-induced emesis in the dog. RG 12915 has no significant gastroprokinetic activity in the same species[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
360.88
Formula
C20H25ClN2O2
CAS 号
136174-04-4
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]. Fitzpatrick LR, et al. RG 12915: a potent 5-hydroxytryptamine-3 antagonist that is an orally effective inhibitor of cytotoxic drug-induced emesis in the ferret and dog. J Pharmacol Exp Ther. 1990 Aug;254(2):450-5.
Vemurafenib (PLX4032) is a first-in-class, selective, potent inhibitor of B-RAF kinase, with IC50s of 31 and 48 nM for RAFV600E and c-RAF-1, respectively[1][4]. Vemurafenib induces cell autophagy[5].
IC50 & Target[1]
B-RafV600E
31 nM (IC50)
c-Raf-1
48 nM (IC50)
体外研究 (In Vitro)
Vemurafenib (PLX4032) selectively blocks the RAF/MEK/ERK pathway in BRAF mutant cells[1]. RG7204 is a potent inhibitor of proliferation in those expressing RAFV600E but not BRAFWT in 17 melanoma cell lines. Vemurafenib (RG7204) induces MEK and ERK phosphorylation at high concentrations in CHL-1 cells[2]. Ectopic expression of EGFR in melanoma cells is sufficient to cause resistance to PLX4032[3].
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)
Vemurafenib (PLX4032, 20, 25, 75 mg/kg, p.o.) causes dose-dependent inhibition of tumor growth, with higher exposures resulting in tumor regression of BRAF mutant xenografts[1]. RG7204 (12.5, 25, and 75 mg/kg, p.o.) significantly inhibits tumor growth and induced tumor regression in mice bearing LOX tumor 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.
Clinical Trial
分子量
489.92
Formula
C23H18ClF2N3O3S
CAS 号
918504-65-1
中文名称
维罗非尼；维罗菲尼；威罗菲尼；唯罗非尼
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Bollag G, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature, 2010, 467(7315), 596-599.
[2]. Yang H, et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models. Cancer Res, 2010, 70(13), 5518-5527.
[3]. Prahallad A, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature, 2012, 483(7387), 100-103.
[4]. Shelledy L, et al. Vemurafenib: First-in-Class BRAF-Mutated Inhibitor for the Treatment of Unresectable or MetastaticMelanoma. J Adv Pract Oncol. 2015 Jul-Aug;6(4):361-5.
[5]. Wang W, et al. Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib.J Clin Endocrinol Metab. 2017 Feb 1;102(2):634-643.
Cell Assay [2]
Briefly, cells are plated in 96-well microtiter plates at a density of 1,000 to 5,000 cells per well in a volume of 180 μL. For the assay, Vemurafenib (RG7204) is prepared at 10 times the final assay concentration in media containing 1% DMSO. Twenty-four hours after cell plating, 20 μL of the appropriate dilution are added to plates in duplicate. The plates are assayed for proliferation 6 days after the cells are plated according to the procedure.
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 [2]
Athymic nude mice, are with ages 13 to 14 weeks, and weighing approximately 23 to 25 g. For the LOX xenografts, 2×106 cells in 0.2 mL of PBS are injected s.c. into the right lateral flank. Vemurafenib (RG7204), formulated as MBP, is suspended at the desired concentration as needed for each dose group in an aqueous vehicle containing 2% Klucel LF and adjusted to pH 4 with dilute HCl. NSC 362856 is of 250-mg capsules. Capsules are opened and combined into one bulk supply. To prepare the stock dosing material, NSC 362856 is first dissolved in 100% DMSO followed by dilution with saline to form a final milky white suspension in 10% DMSO/90% saline (pH 3.4).
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]. Bollag G, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature, 2010, 467(7315), 596-599.
[2]. Yang H, et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models. Cancer Res, 2010, 70(13), 5518-5527.
[3]. Prahallad A, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature, 2012, 483(7387), 100-103.
[4]. Shelledy L, et al. Vemurafenib: First-in-Class BRAF-Mutated Inhibitor for the Treatment of Unresectable or MetastaticMelanoma. J Adv Pract Oncol. 2015 Jul-Aug;6(4):361-5.
[5]. Wang W, et al. Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib.J Clin Endocrinol Metab. 2017 Feb 1;102(2):634-643.
Idasanutlin (RG7388) is a potent and selective MDM2 antagonist, inhibiting p53-MDM2 binding, with an IC50 of 6 nM.
IC50 & Target
IC50: 6 nM (p53-MDM2)[1]
体外研究 (In Vitro)
Idasanutlin (RG7388) inhibits cell proliferation with IC50 of 30 nM, and induces dose-dependent p53 stabilization, cell cycle arrest, as well as cell apoptosis in cancer cells expressing wild-type p53[1]. Idasanutlin (RG7388) (300 nM or 1.8 μM) induces apoptosis in SJSA osteosarcoma cells[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)
Idasanutlin (RG7388, 25 mg/kg p.o.) results in tumor growth inhibition and regression, in the mouse SJSA human osteosarcoma xenograft model[1]. Idasanutlin (RG7388) induces induction of apoptosis and antiproliferation, in the SJSA xenograft model[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.
Clinical Trial
分子量
616.48
Formula
C31H29Cl2F2N3O4
CAS 号
1229705-06-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Ding Q, et al. Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development. J Med Chem. 2013 Jul 25;56(14):5979-83.
[2]. Higgins B, et al. Preclinical optimization of MDM2 antagonist scheduling for cancer treatment by using a model-based approach. Clin Cancer Res. 2014, 20(14), 3742-3752.
Cell Assay [1]
Cell proliferation is evaluated by the tetrazolium dye assay. The concentration at which 50% inhibition (IC50) or 90% inhibition (IC90) of cell proliferation is determined from the linear regression of a plot of the logarithm of the concentration versus percent inhibition.
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 [2]
At 10 to 12 weeks of age, mice are implanted with a 1:1 mixture of human SJSA osteosarcoma cells (ATCC) suspended in phenol-free Matrigel and PBS. Mice are implanted in the right flank at a concentration of 5×106 cells in 0.2 mL total volume. At approximately day 10, animals are randomized according to tumor volume, so that all groups of 10 randomized mice have similar starting mean tumor volumes of 100 to 250 mm3. Idasanutlin (RG7388) is administered as an amorphous solid dispersion microbulk precipitate powder containing 30% drug substance and 70% hydroxypropyl methylcellulose acetate succinate polymer that is reconstituted immediately before administration as a suspension in Klucel/Tween, and remaining suspension is discarded after dosing.
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]. Ding Q, et al. Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development. J Med Chem. 2013 Jul 25;56(14):5979-83.
[2]. Higgins B, et al. Preclinical optimization of MDM2 antagonist scheduling for cancer treatment by using a model-based approach. Clin Cancer Res. 2014, 20(14), 3742-3752.
GDC-0077 (RG6114) is a potent, orally available, and selective PI3Kα inhibitor (IC50=0.038 nM). GDC-0077 (RG6114) exerts its activity by binding to the ATP binding site of PI3K, thereby inhibiting the phosphorylation of PIP2 to PIP3. GDC-0077 (RG6114) is more selective for mutant versus wild-type PI3Kα[1].
IC50 & Target[1]
PI3Kα
0.038 nM (IC50)
体外研究 (In Vitro)
GDC-0077 (RG6114) is >300-fold more selective for PI3Kα over the other class I PI3K isoforms (β, δ, and γ) and >2000-fold more selective over PIK family members. GDC-0077 selectively degrades mutant PI3Kα in a proteasome-dependent fashion resulting in reduction of PI3K pathway activity biomarkers such as pAKT and pPRAS40, inhibition of cell proliferation, and increased apoptosis in human PIK3CA-mutant breast cancer cell lines to a greater extent when compared to PIK3CA wild-type 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)
GDC-0077 (p.o.) results in tumor regressions, induction of apoptosis, and a reduction of pAKT, pPRAS40, and pS6RP in a dose-dependent fashion in patient-derived PIK3CA-mutant breast cancer xenograft models[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.
Clinical Trial
分子量
407.37
Formula
C18H19F2N5O4
CAS 号
2060571-02-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. R Hong, Abstract PD4-14: GDC-0077 is a selective PI3Kalpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies. 2017 San Antonio Breast Cancer Symposium.
RO4929097 (RG-4733) is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively[1].
IC50 & Target
IC50: 4 nM (γ secretase)[1]
体外研究 (In Vitro)
RO4929097 inhibits the production of ICN reducing the expression of the downstream Notch target, Hes1, producing a less transformed morphology in A549 cells. RO4929097 inhibits Notch processing in human tumor-derived cells[1]. RO4929097 (1 µM) inhibits the growth of breast cancer cells, and the inhibition is 20% for SUM149 and 10% for SUM190 cells. RO4929097 does not have a marked effect in invasiveness of SUM149 cells. RO4929097 significantly reduces colony formation by both cell lines with the effect being more notable in SUM149 than by SUM190 cells[2]. RO4929097 inhibits proliferation, anchorage independent growth, and sphere formation of primary melanoma cells in vitro[3].
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)
RO4929097 (3-60 mg/kg, p.o.) results in significant tumor growth inhibition in nude mice bearing A549 NSCLC xenografts, compared with vehicle-treated animals. When mice are treated with 60 mg/kg RO4929097 twice daily with the 7+/14- schedule, treatment initially causes regression of established A549 tumors[1]. RO4929097 impairs the growth of primary melanoma cells in vivo. The percentage of secondary tumors formed by RO4929097-treated cells is lower; the secondary tumors formed by RO4929097-treated cells are smaller; a significant delay in tumor formation by the RO4929097-treated cells compared to the vehicle-treated ones is observed in mice injected with 104 cells in vivo[3].
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.
Clinical Trial
分子量
469.40
Formula
C22H20F5N3O3
CAS 号
847925-91-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Luistro L, et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res. 2009, 69(19), 7672-7680.
[2]. Debeb BG, et al. Pre-clinical studies of Notch signaling inhibitor RO4929097 in inflammatory breast cancer cells. Breast Cancer Res Treat. 2012.
[3]. Huynh C, et al. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. PLoS One. 2011, 6(9), e25264.
Cell Assay [2]
The IBC cell lines SUM149 and SUM190 are seeded at a density of 5 × 104 cells. The next day, they are treated with vehicle or increasing doses of RO4929097, ranging from 0.1 nM to 10 μM. After 72 hrs, cells are trypsinized and viable cells counted with a hemocytometer.
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: RO4929097-treated mice are orally dosed with suspensions at 3 to 60 mg/kg RO4929097 according to the indicated regimens. In the Calu-6 xenograft model, RO4929097 is dosed at 60 mg/kg/d every other week for 4 weeks (7+/7- × 2 cycles). For all other xenograft models, RO4929097 is dosed once daily at 10 mg/kg for 21 days. Statistical analysis is determined by Mann-Whitney rank-sum test, one-way ANOVA, and post hoc Bonferroni t test. Differences between groups are considered significant when P ≤ 0.05. A549 tumors from vehicle-treated and selected RO4929097-treated groups are collected and fixed in 10% zinc-formalin overnight, processed, paraffin-embedded, sectioned at 5 μM, and stained with H&E for histopathology assessment. An Olympus BX51 microscope (×40 objective) mounted with a Nikon DS-Fi1 using the NIS-Elements F2.20 program collected the histology pictures. For Western blot analysis, three A549 tumors from each group, 7 (60 mg/kg) or 21 days (3 and 30 mg/kg), are flash-frozen. Collagen type V is detected using the H-200 antibody at a dilution of 1:1,000, and MFAP5 is detected using the antibody at a dilution of 1:1,000.
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]. Luistro L, et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res. 2009, 69(19), 7672-7680.
[2]. Debeb BG, et al. Pre-clinical studies of Notch signaling inhibitor RO4929097 in inflammatory breast cancer cells. Breast Cancer Res Treat. 2012.
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