THZ2

• CAT Number: I002040
• CAS Number: 1604810-84-5
• Molecular Formula: C31H28ClN7O2
• Molecular Weight: 566.05
• Purity: ≥95%
• Synonyms: THZ2; THZ-2; (Z)-N-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-3-((Z)-((E)-4-(dimethylamino)-1-hydroxybut-2-en-1-ylidene)amino)benzimidic acid
• Target: Cyclin-Dependent Kinases
• Solubility: DMSO: ≥ 39 mg/mL
• Storage: Store at -20°C
• IC50: 13.9 nM
• IUPAC Name: N-[3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]phenyl]-3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]benzamide
• InChI: InChI=1S/C31H28ClN7O2/c1-39(2)15-7-14-28(40)35-21-9-5-8-20(16-21)30(41)36-22-10-6-11-23(17-22)37-31-34-19-26(32)29(38-31)25-18-33-27-13-4-3-12-24(25)27/h3-14,16-19,33H,15H2,1-2H3,(H,35,40)(H,36,41)(H,34,37,38)/b14-7+
• InChIKey: FONRCZUZCHXWBD-VGOFMYFVSA-N
• SMILES: CN(C)C/C=C/C(=O)NC1=CC=CC(=C1)C(=O)NC2=CC=CC(=C2)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl

THZ2（Cat No.:I002040）is a selective inhibitor of cyclin-dependent kinase 7 (CDK7), an essential enzyme involved in transcriptional regulation and cell cycle progression. By targeting CDK7, THZ2 disrupts the phosphorylation of RNA polymerase II, hindering transcription of genes critical for cancer cell survival and proliferation. This compound has shown promise in preclinical studies, particularly in cancers characterized by high transcriptional activity, such as triple-negative breast cancer. THZ2’s ability to sensitize cancer cells to chemotherapy and its role in modulating oncogenic pathways make it a valuable tool in cancer research and therapeutic development.

Reference

1. Mol Cancer Ther. 2017 Sep;16(9):1739-1750. doi: 10.1158/1535-7163.MCT-17-0078.
Epub 2017 Jun 1.
Preclinical Efficacy and Molecular Mechanism of Targeting CDK7-Dependent
Transcriptional Addiction in Ovarian Cancer.
Zhang Z(1)(2), Peng H(1), Wang X(3), Yin X(4)(5), Ma P(1), Jing Y(1), Cai MC(2),
Liu J(2), Zhang M(4)(5), Zhang S(6), Shi K(6), Gao WQ(1)(6), Di W(4)(5), Zhuang
G(7)(5).
Author information:
(1)State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem
Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong
University, Shanghai, China.
(2)State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer
Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University,
Shanghai, China.
(3)Department of Obstetrics and Gynecology, Tongren Hospital, Shanghai Jiao Tong
University School of Medicine, Shanghai, China.
(4)Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine,
Shanghai Jiao Tong University, Shanghai, China.
(5)Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of
Medicine, Shanghai Jiao Tong University, Shanghai, China.
(6)School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao
Tong University, Shanghai, China.
(7)State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem
Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong
University, Shanghai, China. .
Ovarian cancer remains a significant cause of gynecologic cancer mortality, and
novel therapeutic strategies are urgently needed in clinic as new treatment
options. We previously showed that BET bromodomain inhibitors displayed promising
efficacy for the treatment of epithelial ovarian cancer by downregulating pivot
transcription factors. However, the potential antitumor activities and molecular
mechanisms of other epigenetic or transcriptional therapies have not been
systematically determined. Here, by performing an unbiased high-throughput drug
screen to identify candidate compounds with antineoplastic effects, we identified
THZ1, a recently developed covalent CDK7 inhibitor, as a new
transcription-targeting compound that exerted broad cytotoxicity against ovarian
tumors. Mechanistically, CDK7 represented a previously unappreciated actionable
vulnerability in ovarian cancer, and CDK7 inhibition led to a pronounced
dysregulation of gene transcription, with a preferential repression of
E2F-regulated genes and transcripts associated with super-enhancers. Our findings
revealed the molecular underpinnings of THZ1 potency and established
pharmaceutically targeting transcriptional addiction as a promising therapeutic
strategy in aggressive ovarian cancer. Mol Cancer Ther; 16(9); 1739-50. ©2017
AACR.