1223498-69-8
1223498-69-8 structure
- Name: BAY 1000394
- Chemical Name: (2R,3R)-3-[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol
- CAS Number: 1223498-69-8
- Molecular Formula: C18H21F3N4O3S
- Molecular Weight: 430.44500
- Catalog: Research Areas Cancer
- Create Date: 2017-09-29 04:57:44
- Modify Date: 2024-01-03 13:52:41
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Roniciclib is an orally bioavailable pan-cyclin dependent kinase (CDK) inhibitor, with IC50s of 5-25 nM for CDK1, CDK2, CDK3, CDK4, CDK7 and CDK9.
| Name | (2R,3R)-3-[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol |
|---|---|
| Synonyms | BAY 1000394 |
| Description | Roniciclib is an orally bioavailable pan-cyclin dependent kinase (CDK) inhibitor, with IC50s of 5-25 nM for CDK1, CDK2, CDK3, CDK4, CDK7 and CDK9. |
|---|---|
| Related Catalog | |
| Target |
Cdk1/cyclin B:7 nM (IC50) CDK2/cyclinE:9 nM (IC50) CDK4/cyclin D:11 nM (IC50) CDK9/cyclinT1:5 nM (IC50) CDK7/Cyclin H/MAT1:25 nM (IC50) |
| In Vitro | Roniciclib (BAY 1000394) inhibits the kinase activity of the cell-cycle CDKs CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclinDwith IC50 values of 7, 9, and 11 nM, respectively. The transcriptional CDKs CDK9/cyclin T1 and CDK7/cyclin H/MAT1 are inhibited in a similar range (5 and 25 nM)[1]. Roniciclib potently inhibits the proliferation of various human and murine tumor cell lines with a very balanced profile (mean IC50 on human tumor cells: 16 nM)[2]. |
| In Vivo | Tumor growth is strongly inhibited in a dose-dependent manner with T/C values of 0.19 at the lower dose and of 0.02 (tumor regression) at the higher dose. Furthermore, Roniciclib strongly inhibits growth of HeLa-MaTu tumors that have been grown to a size of approximately 50mm2 before start of treatment (day 8 after inoculation). Treatment with Roniciclib at doses of 1.5 and 1 mg/kg slow tumor growth to T/C values of 0.15 and 0.62, respectively. Addition of Roniciclib to cisplatin result in a strong tumor growth inhibition with T/C values of 0.01 (1.0 mg/kg Roniciclib) and -0.02 (1.5 mg/kg Roniciclib)[1]. Roniciclib has low blood clearance rates in mouse, rat, and dog (0.51, 0.78, and 0.50 Lh-1kg-1, respectively) [2]. |
| Animal Admin | Mice[1] Athymic mice bearing established HeLa-MaTu xenograft tumors of approx. 25 mm2 in size are treated orally with Roniciclib (BAY 1000394) at doses of 0.5, 1.0, 1.5, and 2.0 mg/kg once daily for 21 days. Treatment is well tolerated as no body weight loss below the initial body weight is observed. Additional groups of mice are treated on a cyclic intermittent dosing schedule at doses of 1.5, 2.0, and 2.5 mg/kg twice daily for 2 days followed by 5 days without treatment (2 on/5 off). In total, 3 treatment cycles are completed[1]. |
| References |
| Molecular Formula | C18H21F3N4O3S |
|---|---|
| Molecular Weight | 430.44500 |
| Exact Mass | 430.12900 |
| PSA | 116.57000 |
| LogP | 4.99360 |
| Storage condition | -20℃ |