Description
Product Usage Information
TL12-186 is supplied as a lyophilized powder. For a 5 mM stock, reconstitute 5 mg of powder in 1.07 mL 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
TL12-186 is a pan-kinase PROTAC (proteolysis-targeting chimera) compound that links a cereblon (CRBN)-recruiting pomalidomide moiety and a promiscuous kinase inhibitor (1). The inhibitor moiety competes with ATP for binding to the kinase catalytic site. TL12-186 exhibits a binding affinity (IC ) of 12 nM for CRBN. At a concentration of 1 μM, TL12-186 induces >90% inhibition of 193 kinases according to a kinase selectivity assay. When administered at 100 nM for four hours in human MOLM-14 and MOLT-4 cells, TL12-186 degrades 28 kinases by 50% or more, including BTK, PTK2, PTK2B, FLT3, AURKA/B, TEC, ULK1, ITK, and nine members of the CDK family. This compound is valuable for assessing the susceptibility of kinases to degradation in various model systems. In one study, a platelet model system treated with TL12-186 showed that BTK degradation has advantages over simple inhibition in preventing thrombosis (2). Additionally, TL12-186 was used to experimentally validate a computational model that predicts which substrate lysines are most likely to be ubiquitinated by CRBN-dependent PROTACs (3).
