Delving into the Latest Updates on LL-K9-3 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CDK9 x cyclin-T1

Mechanism

CDK9 inhibitors(Cyclin-dependent kinase 9 inhibitors), cyclin-T1 inhibitors(cyclin T1 inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Prostatic Cancer

Inactive Indication-

Originator Organization

Chinese Academy of Sciences

Active Organization

Chinese Academy of Sciences

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Aberrant hyperactivation of cyclins results in carcinogenesis and therapy resistance in cancers. Direct degradation of the specific cyclin or cyclin-dependent kinase (CDK)-cyclin complex by small-molecule degraders remains a great challenge. Here, we applied the first application of hydrophobic tagging to induce degradation of CDK9-cyclin T1 heterodimer, which is required to keep productive transcription of oncogenes in cancers. LL-K9-3 was identified as a potent small-molecule degrader of CDK9-cyclin T1. Quantitative and time-resolved proteome profiling exhibited LL-K9-3 induced selective and synchronous degradation of CDK9 and cyclin T1. The expressions of androgen receptor (AR) and cMyc were reduced by LL-K9-3 in 22RV1 cells. LL-K9-3 exhibited enhanced anti-proliferative and pro-apoptotic effects compared with its parental CDK9 inhibitor SNS032 and suppressed downstream signaling of CDK9 and AR more effectively than SNS032. Moreover, LL-K9-3 inhibited AR and Myc-driven oncogenic transcriptional programs and exerted stronger inhibitory effects on several intrinsic target genes of AR than the monomeric CDK9 PROTAC (Thal-SNS032).

100 Deals associated with LL-K9-3

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