Formulation: A solid
Formal Name: 4-((2-(4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)-2-oxoethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
Purity: ≥95%
Formula Markup: C39H40ClN9O8S
Formula Weight: 830,3
Shelf life (days): 1095
Notes: AP-1 is a miniaturized proteolysis-targeting chimera (PROTAC) that contains an anaplastic lymphoma kinase (ALK) ligand connected to the E3 ubiquitin ligase ligand (±)-thalidomide (Item No. 14610) by an ultrashort linker.{65740} It degrades the ALK fusion protein NPM-ALK in Karpas-299 cells, where it is highly expressed, when used at concentrations ranging from 10 to 300 nM, an effect that can be blocked by the proteasome inhibitor MG-132. It also degrades the ALK fusion protein EML4-ALK and ALK containing the phenylalanine-to-leucine substitution mutation at position 1174 (ALKF1174L) expressed in SN-N-SH and NCI H3122 cells, respectively. AP-1 is cytotoxic to ALK-dependent Karpas-299 cells (IC50 = 0.1265 nM) but not non-ALK-dependent THP-1 cells (IC50 = 2,704 nM). It reduces tumor volume in an NCI H3122 mouse xenograft model when administered at doses of 25, 50, and 100 mg/kg.
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