104 The molecular context of vulnerability for CDK9 suppression in melanoma

Abstract

In unpublished studies, we recently found that a cyclin-dependent kinase 9 (CDK9) degrader (Thal-SNS-032, TS-032) selectively inhibited BRAF/NRAS wild type melanomas. We now confirm this finding using another competitive CDK9 inhibitor, NVP-2. To further explore the context of this vulnerability, we undertook a large RNA seq analysis of 9 pigment cell lines (1 triple wild-type melanoma line, 2 uveal lines, 2 BRAF-mutated, 2 NRAS-mutated, 1 NF1-mutated, and 1 immortalized melanocyte line) in order to uncover transcriptional programs which may be preferentially extinguished or activated by TS-032 and NVP-2.