Senexin C
- CAS No.
- 2375554-02-0
- Chemical Name:
- Senexin C
- Synonyms
- Senexin C;Senexin C, 10 mM in DMSO
- CBNumber:
- CB811275596
- Molecular Formula:
- C28H27N5O
- Molecular Weight:
- 449.56
- MDL Number:
- MOL File:
- 2375554-02-0.mol
Senexin C Chemical Properties,Uses,Production
Description
Senexin C exhibits potent CDK8/19 inhibitory activity with high selectivity. Senexin C is more metabolically stable and provides a more sustained inhibition of CDK8/19-dependent cellular gene expression when compared with the prototype inhibitor Senexin B. Senexin C inhibits MV4-11 leukemia growth in a systemic in vivo model with good tolerability.
Uses
Senexin C is a selective and orally active CDK8/19 inhibitor. Senexin C shows a strong tumor-enrichment pharmacokinetic (PK) profile and tumor-pharmacodynamic (PD) marker responses. Senexin C inhibits the growth of MV4-11 leukemia cells with good tolerability[1].
in vivo
Senexin C (2.5 mg/kg, i.v.; 100 mg/kg, p.o.) shows good oral bioavailability[1].
Senexin C (40 mg/kg; p.o.; twice daily for 4 weeks) suppresses the systemic growth of MV4-11 AML with good tolerability[1].
Pharmacokinetic Parameters of Senexin C in eight-week-old female Balb/c mice[1].
| parameters | iv (2.5 mg/kg) | po (100 mg/kg) | ||
| plasma | tumor | plasma | tumor | |
| C0 (μg/mL) | 503 | |||
| Kel (h-1) | 0.93 | 0.06 | 0.2 | 0.1 |
| T1/2 (h) | 0.75 | 12.1 | 3.53 | 7.27 |
| Tmax (h) | 0.58 | 12 | 12 | |
| Cmax (ng/mL or ng/g) | 488 | 144 | 5728 | |
| AUC0-24 h (ng x h/ml or ng x h/g) | 331 | 6408 | 2182 | 88,600 |
| F% | 16.5% | 34.6% |
| Animal Model: | eight-week-old female Balb/c mice ( CT26 tumor mode)[1] |
| Dosage: | 2.5 mg/kg (10 mL/kg of 2.5 mg/mL Senexin C solution in 5% dextrose), 100 mg/kg (10 mL/kg of 10 mg/mL Senexin C solution in 30% propylene glycol/70% PEG-400 vehicle) |
| Administration: | 2.5 mg/kg, i.v.; 100 mg/kg, p.o. |
| Result: | Showed good oral bioavailability. |
| Animal Model: | eight-week-old female NSG mice ( AML model)[1] |
| Dosage: | 40 mg/kg |
| Administration: | p.o.; twice daily, 4 weeks |
| Result: | Suppressed the systemic growth of MV4-11 AML with good tolerability. |
IC 50
CDK8/CycC: 3.6 nM (IC50); CDK19/CycC: 2.9 nM (Kd); CDK8/CycC: 1.4 nM (Kd)
References
[1] Zhang L, et al. A Selective and Orally Bioavailable Quinoline-6-Carbonitrile-Based Inhibitor of CDK8/19 Mediator Kinase with Tumor-Enriched Pharmacokinetics. J Med Chem. 2022; 65(4):3420-3433. DOI:10.1021/acs.jmedchem.1c01951
Senexin C Preparation Products And Raw materials
Raw materials
Preparation Products
Senexin C Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Shanghai Lollane Biological Technology Co.,Ltd. | 021-52996696，15000506266 15000506266 | China | 4601 | 55 | |
| Suzhou youruike Chemical Pharmaceutical Technology Co., Ltd | 15317229551 | 15151849396@163.com | China | 998 | 58 |
| cjbscvictory | 13348960310 13348960310 | 3003867561@qq.com | China | 10523 | 58 |
| Shenyang Zhongshen Zekang Biomedical Technology Research Co., Ltd | 024-024-024-88590548 18341751992 | 757984502@qq.com | China | 929 | 58 |
| Shanghai Yifei Biotechnology Co. , Ltd. | 021-65675885 18964387627 | customer_service@efebio.com | China | 11973 | 58 |
| Shandong Mopai Biotechnology Co., Ltd | 13053322091 13053322091 | admin@mopaikeji.com | China | 4263 | 58 |
| TargetMol Chemicals Inc. | 15002134094 | marketing@targetmol.cn | China | 19727 | 58 |
| Sangon Biotech (Shanghai) Co.,Ltd. | 400-821-026 | Sales@sangon.com | China | 47255 | 58 |