CST, 43407S, HQ461

Product Usage Information
HQ461 is supplied as a lyophilized powder. For a 15 mM stock, reconstitute 5 mg of powder in 965 μL of DMSO. Working concentrations and length of treatment can vary depending on the desired effect.
Storage
Store lyophilized at -20ºC, desiccated. In lyophilized form, the chemical is stable for 24 months. Once in solution, store at -20ºC and use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles .
Background
The cyclin K (CCNK)/CDK12 complex regulates the expression of key proteins in the DNA Damage Response (DDR) (1). HQ461 is a molecular glue that promotes cyclin K degradation by converting CDK12 into a substrate-specific receptor for the DDB1 E3 ubiquitin ligase (2). Although CDK12 is not directly targeted, HQ461-induced degradation of cyclin K disrupts the function of its partner protein, impairing kinase activity, downregulating DDR genes, and ultimately leading to cell death (2,3). In the non-small cell lung cancer cell line A549, HQ461 has an IC of 1.3 µM (2).