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. Author manuscript; available in PMC: 2020 Oct 23.
Published in final edited form as: J Med Chem. 2018 Jul 9;61(14):6350–6363. doi: 10.1021/acs.jmedchem.8b00810

Figure 1. Molecular docking and thermodynamic analysis of N-Me-AVPF-NH2, LCL161, and compound 1 followed by selectivity studies against the BIR3 domains of XIAP, cIAP1, and cIAP2.

Figure 1.

a) Docking pose of N-Me-AVPF-NH2 into the binding pocket of the BIR3 domain of XIAP (PDB ID 2OPZ). b) Isothermal Titration Calorimetry (ITC) curve for the binding between the BIR3 domain of XIAP and N-Me-AVPF-NH2. c) DELFIA displacement curves relative to the compound N-Me-AVPF-NH2 tested against the BIR3 domains of XIAP, cIAP1, and cIAP2, respectively (IC50 values 108.2 nM, 48.2 nM, and 209 nM, for XIAP, cIAP1, and cIAP2, respectively). d) Docking pose of the clinical compound LCL161 into the binding pocket of the BIR3 domain of XIAP (PDB ID 2OPZ). e) Isothermal Titration Calorimetry (ITC) curve for the interaction between the BIR3 domain of XIAP and LCL161. f) DELFIA displacement curves relative to the compound LCL161 tested against the BIR3 domains of XIAP, cIAP1, and cIAP2 (IC50 values 52.7 nM, 10.4 nM, and 12.9 nM, for XIAP, cIAP1, and cIAP2, respectively). g) Docking pose of the compound 1 into the binding pocket of the BIR3 domain of XIAP (PDB ID 2OPZ). The XIAP BIR3 residue Lys311, interacting with the phosphonate group, is highlighted. h) Isothermal Titration Calorimetry (ITC) curve for the binding between the BIR3 domain of XIAP and compound 1. i) DELFIA displacement curves relative to the compound 1 tested against the BIR3 domain of XIAP, cIAP1, and cIAP2 (IC50 values 35 nM, 197.6 nM, and 364.3 nM, for XIAP, cIAP1, and cIAP2, respectively).