| Identification | Back Directory | [Name]
CDK7-IN-1 | [CAS]
1604810-84-5 | [Synonyms]
THZ2
CS-1182
CDK7-IN-1
THZ2,CDK7-IN-1
THZ-2;THZ2;THZ 2
(E)-N-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-3-(4-(dimethylamino)but-2-enamido)benzamide
Benzamide, N-[3-[[5-chloro-4-(1H-indol-3-yl)-2-pyrimidinyl]amino]phenyl]-3-[[(2E)-4-(dimethylamino)-1-oxo-2-buten-1-yl]amino]- | [Molecular Formula]
C31H28ClN7O2 | [MDL Number]
MFCD28716099 | [MOL File]
1604810-84-5.mol | [Molecular Weight]
566.05 |
| Chemical Properties | Back Directory | [density ]
1.379±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≥28.3 mg/mL in DMSO; insoluble in H2O; ≥2.96 mg/mL in EtOH with gentle warming and ultrasonic | [form ]
solid | [pka]
13.06±0.70(Predicted) | [color ]
Light yellow to khaki |
| Hazard Information | Back Directory | [Uses]
THZ2 is a potent and selective CDK7 inhibitor with an IC50 of 13.9 nM. | [Biological Activity]
thz2 is a potent and selective cdk7 inhibitor (ic50=13.9 nm).cyclin-dependent kinase (cdk) is a group of serine/threonine kinases. it is activated by binding to cyclin and participates in the regulation of cell cycle.thz2 selectively targets cdk7 and potently blocks the proliferation of triple-negative breast cancer (tnbc) cells and induces apoptotic cell death without causing alteration in cell cycle. the low nanomolar dose of thz2 also inhibits the clonogenic growth of tnbc cells with ic50 of 10 nm.thz2 is well tolerant in mice as 10 mg/kg intraperitoneal treatment of thz2 twice daily does not cause weight loss or behavioral changes. thz2 treatment also significantly reduces the tumor growth rate mice. in addition, both acute (50 hr) or chronic (25 days) exposure to thz markedly decreases ctd phosphorylation of rnapii at all three phosphorylation sites as indication of cdk7 being efficiently targeted. | [in vivo]
THZ2 (10 mg/Kg) markedly reduces the growth rate of tumors in mice and demonstrates an anti-tumor activity. Compared to vehicle-treated tumors, tumor tissues isolated from mice treated with THZ2 has reduced proliferation and increased apoptosis, as indicated by immunostaining against Ki67 and cleaved Caspase 3 respectively. THZ2 in NOD-SCID mice leads to reduced body weight, suggesting that THZ2 mayt be less well-tolerated in this particular mouse strain[1]. | [IC 50]
CDK7: 13.9 nM (IC50); CDK1: 96.9 nM (IC50); CDK2: 222 nM (IC50); CDK5: 134 nM (IC50); CDK9: 194 nM (IC50); CDK8: 6830 nM (IC50) | [References]
1. wang y, zhang t, kwiatkowski n et al. cdk7-dependent transcriptional addiction in triple-negative breast cancer. cell. 2015 sep 24;163(1):174-86. |
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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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