THAL-SNS-032

InvivoChem Cat #:V3487CAS #:2139287-33-3Purity >=98%

Description: THAL-SNS-032 is a novel, potent and selective CDK9 degrader baed on PROTAC technology to degrade CDK9. THAL-SNS-032 is composed of a CDK-binding SNS-032 ligand linked to a thalidomide which is E3 ligase ligand that binds the E3 ubiquitin ligase Cereblon (CRBN). Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. THAL-SNS-032 induced rapid degradation of CDK9 without affecting the levels of other SNS-032 targets. Moreover, the transcriptional changes elicited by THAL-SNS-032 were more like those caused by NVP-2 than those induced by SNS-032. Notably, compound washout did not significantly reduce levels of THAL-SNS-032-induced apoptosis, suggesting that CDK9 degradation had prolonged cytotoxic effects compared with CDK9 inhibition. Thus, the findings suggest that thalidomide conjugation represents a promising strategy for converting multi-targeted inhibitors into selective degraders and reveal that kinase degradation can induce distinct pharmacological effects compared with inhibition.

References: Nat Chem Biol. 2018 Feb; 14(2):163-170.

Related CAS#: 345627-90-9 (HCl); 2139287-33-3 (THAL-SNS-032, a selective CDK9 degrader)

345627-90-9 (HCl); 2139287-33-3 (THAL-SNS-032, a selective CDK9 degrader)

-20C for 3 years in powder form

Synonym: THAL-SNS 032; THAL SNS-032; THAL-SNS032; THAL-SNS-032; THALSNS032; THAL SNS 032; THALSNS-032
Chemical Name: N-(5-(((5-(tert-Butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-(14-((2-(2, 6-dioxopiperidin-3-yl)-1, 3-dioxoisoindolin-4-yl)amino)-2-oxo-6, 9, 12-trioxa-3-azatetradecyl)piperidine-4-carboxamide
InChi Key: BXDZOYLPNAIDOC-UHFFFAOYSA-N
InChi Code: InChI=1S/C40H52N8O10S2/c1-40(2, 3)29-21-43-32(58-29)24-59-33-22-44-39(60-33)46-35(51)25-9-13-47(14-10-25)23-31(50)42-12-16-56-18-20-57-19-17-55-15-11-41-27-6-4-5-26-34(27)38(54)48(37(26)53)28-7-8-30(49)45-36(28)52/h4-6, 21-22, 25, 28, 41H, 7-20, 23-24H2, 1-3H3, (H, 42, 50)(H, 44, 46, 51)(H, 45, 49, 52)
SMILES Code: O=C(C1CCN(CC(NCCOCCOCCOCCNC2=CC=CC(C(N3C(CC4)C(NC4=O)=O)=O)=C2C3=O)=O)CC1)NC5=NC=C(SCC6=NC=C(C(C)(C)C)O6)S5