TL 12-186

TL12-186 is a multikinase degrading PROTAC.

Product information

CAS Number: 2250025-88-6

Molecular Weight: 931.46

Formula: C44H51ClN10O9S

Chemical Name: N-(2-(2-(2-(4-(4-((5-Chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)phenyl)piperazin-1-yl)ethoxy)ethoxy)ethyl)-2-((2-(2, 6-dioxopiperidin-3-yl)-1, 3-dioxoisoindolin-4-yl)amino)acetamide

Smiles: CC(C)S(=O)(=O)C1=CC=CC=C1NC1=NC(NC2=CC=C(C=C2)N2CCN(CCOCCOCCNC(=O)CNC3=CC=CC4C(=O)N(C5CCC(=O)NC5=O)C(=O)C=43)CC2)=NC=C1Cl

InChiKey: YNGWQHGVASHCBK-UHFFFAOYSA-N

InChi: InChI=1S/C44H51ClN10O9S/c1-28(2)65(61,62)36-9-4-3-7-33(36)50-40-32(45)26-48-44(52-40)49-29-10-12-30(13-11-29)54-19-17-53(18-20-54)21-23-64-25-24-63-22-16-46-38(57)27-47-34-8-5-6-31-39(34)43(60)55(42(31)59)35-14-15-37(56)51-41(35)58/h3-13,26,28,35,47H,14-25,27H2,1-2H3,(H,46,57)(H,51,56,58)(H2,48,49,50,52)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

TL12-186 displays >90% inhibition of 193 kinases at a screening concentration of 1 μM. TL12-186 displays potent binding to CRBN (IC50=12 nM) using an AlphaScreen engagement assay. TL12-186 (1-10000 nM; 2 days) exhibits a CRBN-dependent pharmacological effect, displaying 13 to 15-fold more potent inhibition of survival of the WT cells than the CRBN-/- cells. TL12-186 (10-10000 nM; 4 hours) inhibits STAT1 phosphorylation without causing JAK1/2 degradation.

References:

1. Hai-Tsang Huang, et al. A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader. Cell Chem Biol. 2018 Jan 18;25(1):88-99.e6.

Products are for research use only. Not for human use.