THZ531

• CAT Number: I009802
• CAS Number: 1702809-17-3
• Molecular Formula: C30H32ClN7O2
• Molecular Weight: 558.083
• Purity: ≥95%
• Synonyms: THZ531; THZ-531; THZ 531.;(R,E)-N-(4-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide
• Target: Cyclin-Dependent Kinases
• Solubility: Soluble in DMSO
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• InChI: InChI=1S/C30H32ClN7O2/c1-37(2)15-6-10-27(39)34-21-13-11-20(12-14-21)29(40)38-16-5-7-22(19-38)35-30-33-18-25(31)28(36-30)24-17-32-26-9-4-3-8-23(24)26/h3-4,6,8-14,17-18,22,32H,5,7,15-16,19H2,1-2H3,(H,34,39)(H,33,35,36)/b10-6+/t22-/m1/s1
• InChIKey: RUBYHLPRZRMTJO-MOVYNIQHSA-N
• SMILES: ClC1=CN=C(N[C@H]2CN(C(C3=CC=C(NC(/C=C/CN(C)C)=O)C=C3)=O)CCC2)N=C1C4=CNC5=C4C=CC=C5

THZ531 (CAT: I009802) is a highly potent and selective inhibitor of CDK12 and CDK13, two members of the cyclin-dependent kinase (CDK) family. It acts by binding to the ATP-binding pocket of CDK12/13 and inhibiting their kinase activity. THZ531 has been shown to disrupt the phosphorylation of RNA polymerase II, leading to the downregulation of transcription and subsequent inhibition of cancer cell growth. It displays strong antitumor effects in preclinical models, particularly in cancers driven by transcriptional dependencies such as Ewing sarcoma and triple-negative breast cancer. THZ531 represents a promising therapeutic strategy for targeting transcriptional regulation in cancer cells and is undergoing further investigation for its clinical potential.

Overview of Clinical Research

Originator: Syros Pharmaceuticals
Developer: Dana-Farber Cancer Institute; Syros Pharmaceuticals; Whitehead Institute for Biomedical Research
Class Small molecules
Mechanism of Action: Cyclin-dependent kinase inhibitors; Cyclin-dependent kinase-activating kinase inhibitors; Gene expression modulators; Immunosuppressants
Orphan Drug Status: No

Reference

1: Zhang T, Kwiatkowski N, Olson CM, Dixon-Clarke SE, Abraham BJ, Greifenberg AK,
Ficarro SB, Elkins JM, Liang Y, Hannett NM, Manz T, Hao M, Bartkowiak B,
Greenleaf AL, Marto JA, Geyer M, Bullock AN, Young RA, Gray NS. Covalent
targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors. Nat
Chem Biol. 2016 Oct;12(10):876-84. doi: 10.1038/nchembio.2166. PubMed PMID:
27571479; PubMed Central PMCID: PMC5033074.