compound 11 [PMID: 35653642]   Click here for help

GtoPdb Ligand ID: 12047

PDB Ligand
Compound class: Synthetic organic
Comment: This is a small molecule that was optimised for binding to the pseudokinase (JH2) domain of Janus kinase 2 (JAK2) [1]. It is ~150-fold selective for JH2 compared to the JH1 active kinase site of the enzyme. It binds potently to the JH2 domain with the V617F mutation (Kd 62 nM) that is a known driver of pathogenesis in some myeloproliferative neoplasms. Compound 11 is a potent binder of JAK2 JH2 but it is inactive in cellular assays.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 11
Hydrogen bond donors 5
Rotatable bonds 11
Topological polar surface area 212.93
Molecular weight 599.16
XLogP 4.15
No. Lipinski's rules broken 1
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Canonical SMILES OC(=O)c1cc(ccc1OCc1ccccc1)c1ccc(cc1)NC(=O)n1nc(nc1N)Nc1ccc(cc1)S(=O)(=O)N
Isomeric SMILES Nc1nc(Nc2ccc(S(=O)(=O)N)cc2)nn1C(=O)Nc1ccc(c2cc(C(=O)O)c(OCc3ccccc3)cc2)cc1
InChI InChI=1S/C29H25N7O6S/c30-27-34-28(32-21-11-13-23(14-12-21)43(31,40)41)35-36(27)29(39)33-22-9-6-19(7-10-22)20-8-15-25(24(16-20)26(37)38)42-17-18-4-2-1-3-5-18/h1-16H,17H2,(H,33,39)(H,37,38)(H2,31,40,41)(H3,30,32,34,35)
1. Liosi ME, Ippolito JA, Henry SP, Krimmer SG, Newton AS, Cutrona KJ, Olivarez RA, Mohanty J, Schlessinger J, Jorgensen WL. (2022)
Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands.
J Med Chem, 65 (12): 8380-8400. [PMID:35653642]