Figure 9.

Chemical structures of true binder hits of ACVR1 uniquely identified by FRAGSITE but not FINDSITE^comb2.0 comprising diverse scaffolds for fragment-based drug design. Three compounds labeled red have a conservatively estimated K_d < 1 μM based on the reference ΔT_m values observed in this study for the known affinity of kinase inhibitors NSC760766 (Vandetanib, K_d of 0.15 μM),⁶⁸ NSC732517 (Dasatinib, K_d of 0.62 μM),⁶⁸ and NSC749005 (Crizotinib, K_d of 0.44 μM)⁶⁸ and K02288 (IC50 of 1.1 nM),⁷⁰ 8.0, 4.0, 8.0, and 13.0 °C, respectively. The rest of the true hit binders have estimated affinity for ACVR1 at the micromolar level based on the above reference compounds and the reported method of estimating binding affinity based on thermal shift assays.⁶³