Formulation: A solid
Formal Name: (2S,4R)-1-((S)-2-(7-(4-((R)-3-((4-(N-(4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoyl)sulfamoyl)-2-((trifluoromethyl)sulfonyl)phenyl)amino)-4-(phenylthio)butyl)piperazin-1-yl)-7-oxoheptanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide
Purity: ≥98%
Formula Markup: C77H96ClF3N10O10S4
Formula Weight: 1542,4
Shelf life (days): 1460
CAS Number: 2365172-42-3
Notes: DT2216 is a proteolysis-targeting chimera (PROTAC) composed of the Bcl-2 family inhibitor ABT-263 (Item No. 11500) conjugated to a von Hippel-Lindau (VHL) E3 ligase ligand.{65683} It selectively induces degradation of Bcl-xL in MOLT-4 T cell acute lymphoblastic leukemia (T-ALL) cells with a 50% degradation concentration (DC50) value of 63 nM and maximum degradation (Dmax) of 90.8% over washed isolated human platelets with a Dmax of 26% at 3 µM. DT2216 selectively binds to Bcl-xL and Bcl-2 over Bcl-W (Kis = 12.82, 1.82, and 300.9 nM, respectively) but does not induce degradation of Bcl-2 or Bcl-W in RS4;11 B-ALL cells at 1 µM. It is cytotoxic to MOLT-4 cells but not washed isolated human platelets (EC50s = 0.052 and >3 µM, respectively) and induces cleavage of caspase-3 in MOLT-4 cells when used at concentrations of 100 and 300 nM. DT2216 (15 mg/kg) reduces tumor volume and weight in a MOLT-4 mouse xenograft model. It acts synergistically with the Bcl-2 inhibitor ABT-199 (Item No. 16233) in an NCI H146 small cell lung cancer (SCLC) mouse xenograft model and the microtubule-stabilizing anticancer agent docetaxel (Item No. 11637) in an MDA-MB-231 breast cancer mouse xenograft model.
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