TD-165

TD-165 is a proteolysis-targeting chimera (PROTAC) that contains VH 032 (Cay-39982) conjugated to the cereblon (CRBN) inhibitor pomalidomide (Cay-19877). It induces degradation of CRBN in HEK293T cells with a half-maximal degradation concentration (DC50) value of 20. nM. TD-165 (0. µM) increases L-type voltage-gated calcium channel 1.2alpha (Cav1.2alpha) levels in AC16 ventricular cardiomyocytes. It increases left ventricle pressure and heart rate in mice. Intra-articular administration of TD-165 (1. µg/joint) decreases disease severity and subchondral bone plate thickness in a mouse model of osteoarthritis induced by destabilization of the medial meniscus. Formal Name: (2S,4R)-1-((2S)-2-(11-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)undecanamido)-3,3-dimethyl-butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide. CAS Number: 2305936-56-3. Molecular Formula: C46H59N7O8S. Formula Weight: 870.1. Purity: >95%. Formulation (Request formulation change): A solid. Solubility: DMSO: Sparingly soluble: 1-10 mg/ml Ethanol: Slightly soluble: 0.1-1 mg/ml. SMILES: O=C([C@@H](NC(CCCCCCCCCCNC1=C(C(C(N2C3C(NC(CC3)=O)=O)=O)=CC=C1)C2=O)=O)C(C)(C)C)N4[C@H](C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)C[C@H](C4)O. InChi Code: InChI=1S/C46H59N7O8S/c1-28-39(62-27-49-28)30-19-17-29(18-20-30)25-48-41(57)35-24-31(54)26-52(35)45(61)40(46(2,3)4)50-36(55)16-11-9-7-5-6-8-10-12-23-47-33-15-13-14-32-38(33)44(60)53(43(32)59)34-21-22-37(56)51-42(34)58/h13-15,17-20,27,31,34-35,40,47,54H,5-12,16,21-26H2,1-4H3,(H,48,57)(H,50,55)(H,51,56,58)/t31-,34?,35+,40-/m1/s1. InChi Key: KSXVXTSIDVRZBR-IINAPWRYSA-N. Storage: -20°C. Stability: > 4 years.