Antibodies
BAY 1000394
- 貨號 Cat. No.
- S7047
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
BAY 1000394
Catalog No.S7047
BAY 1000394 is an orally bioavailable pan-CDK inhibitor for CDK1/2/3/4/7/9 with IC50 of 5-25 nM. It also potently inhibits Aurora A, Clk2, ARK5, FGFR1, Flt3, and JAK2/3. Phase 1/2.
| Availability |
|---|
The item is temporarily out of stock. Please leave your email address and we will inform you when we have it in stock. Just click the Arrival Notice and leave your email address to get 10% off. Arrival Notice |
Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | BAY 1000394 is an orally bioavailable pan-CDK inhibitor for CDK1/2/3/4/7/9 with IC50 of 5-25 nM. It also potently inhibits Aurora A, Clk2, ARK5, FGFR1, Flt3, and JAK2/3. Phase 1/2. | |||||
|---|---|---|---|---|---|---|
| Targets | CDK1 | CDK2 | CDK4 | CDK9 | CDK7 | |
| IC50 | 7 nM | 9 nM | 11 nM | 5 nM | 25 nM [1] | |
| In vitro | BAY 1000394 inhibits the kinase activity of the cell-cycle CDKs CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D with IC50 values of 7, 9, and 11 nM, respectively. The transcriptional CDKs CDK9/cyclin T1 and CDK7/cyclin H/MAT1 are also inhibited by BAY 1000394 in a similar range (5 and 25 nM), as well as the other CDK family members, classifying BAY 1000394 as a pan-CDK inhibitor. BAY 1000394 simultaneously inhibits cell-cycle progression and of RNA polymerase II-mediated gene transcription. On a panel of 214 non-CDK Ser/Thr and Tyr kinases, 16 additional kinases are found to be inhibited by BAY 1000394 with IC50 values below 100 nM. BAY 1000394 displays broad and uniform inhibitory activity on cancer cell proliferation with IC50s values between 9 and 79 nM (mean 39 nM) for a panel of 40 human lung tumor cell lines, and IC50s between 6 an d 84 nM (mean 37 nM) for a panel of 24 human breast tumor and immortalized cell lines. Within these panels, which represent a broad range of genetic backgrounds (p53, pRB, K-Ras, PGP, etc.), no cell line could be identified that is poorly sensitive towards treatment with BAY 1000394. Antiproliferative activity of BAY 1000394 is associated with the induction of apoptotic cell death. Exposure of asynchronously growing HeLa cells to BAY 1000394 for 24 hours reduces the fraction of cells with 2N content, from 69% to 52% compared with vehicle treated cells and strongly increases the fraction of cells with less than 2N DNA content from 1% to 16%. Only minor shifts are observed for cells in S, G2, or M phase. [1] | |||||
| In vivo | BAY 1000394 shows potent tumor growth inhibition in monotreatment upon oral application in various dosing schedules in a dose-dependent manner, activity in models of treatment-refractory tumors, and efficacy in cell-line–derived as well as in patient tumor–derived models. BAY 1000394 (2 mg/kg) suppresses growth of HeLa-MaTu xenografts tumor with T/C values of 0.03 and signs of tumor regression. BAY 1000394 shows additive efficacy in combination with cisplatin. Addition of BAY 1000394 to cisplatin results in a strong tumor growth inhibition of NCI-H82 SCLC xenograft tumors with T/C values of 0.01 (1.0 mg/kg BAY 1000394) and -0.02 (1.5 mg/kg BAY 1000394). [1] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Kkinase assays | Recombinant CDK1 and CycB-GST fusion proteins, and CDK2 and CycE-GST fusion proteins, are purified from baculovirus-infected Sf9 insect cells. Histon IIIS is used as kinase substrate. Inhibition of kinase activity is determined by substrate phosphorylation assays using 3P-gamma adenosine triphosphate. BAY 1000394 is counter screened against a panel of 220 kinases using the Kinase profiler screen at 500 nM. |
|---|
Cell Assay: [1]
| Cell lines | Human cervical cancer cell HeLa-MaTu |
|---|---|
| Concentrations | ~10 μM |
| Incubation Time | 4 days |
| Method | Proliferation assays are conducted in 96 well plates at densities between 1,000 and 5,000 cells per well in the appropriate medium containing 10% fetal calf serum (FCS). Cells are treated in quadruplicates with serial dilutions of BAY 1000394 for 96 hours followed by quantification of relative cell numbers upon crystal violet staining. BAY 1000394 is profiled on panels of 40 human lung and 24 human breast cell lines using the Oncology Profiling Service. |
Animal Study: [1]
| Animal Models | Human cervical cancer xenografts HeLa-MaTu |
|---|---|
| Dosages | 2 mg/kg |
| Administration | p.o. once daily for 21 days |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01188252 | Recruiting | Neoplasms | Bayer | 2010-08 | Phase 1 |
| NCT01335256 | Completed | Neoplasms | Bayer | 2010-12 | Phase 1 |
| NCT01573338 | Recruiting | Small Cell Lung Carcinoma | Bayer | 2013-02 | Phase 1|Phase 2 |
Chemical Information
| Molecular Weight (MW) | 430.44 |
|---|---|
| Formula | C18H21F3N4O3S |
| CAS No. | 1223498-69-8 |
| Storage | 3 years -20℃Powder |
|---|---|
| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | mg/mL (<1 mM) |
|---|---|---|---|
| Water | mg/mL (<1 mM) | ||
| Ethanol | mg/mL (<1 mM) | ||
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | 2-Butanol, 3-[[2-[[4-[[S(R)]-S-cyclopropylsulfonimidoyl]phenyl]amino]-5-(trifluoromethyl)-4-pyrimidinyl]oxy]-, (2R,3R)- |
|---|
