KP-457

• CAT Number: I046262
• CAS Number: 1365803-52-6
• Molecular Formula: C21H24N2O7S2
• Molecular Weight: 480.55
• Purity: ≥95%
• Synonyms: N-[2-(4-but-2-ynoxyphenyl)sulfonyl-1-[4-(methanesulfonamidomethyl)phenyl]ethyl]-N-hydroxyformamide
• InChI: InChI=1S/C21H24N2O7S2/c1-3-4-13-30-19-9-11-20(12-10-19)32(28,29)15-21(23(25)16-24)18-7-5-17(6-8-18)14-22-31(2,26)27/h5-12,16,21-22,25H,13-15H2,1-2H3
• InChIKey: VIWDSTUVCAZZDF-UHFFFAOYSA-N
• SMILES: CC#CCOC1=CC=C(C=C1)S(=O)(=O)CC(C2=CC=C(C=C2)CNS(=O)(=O)C)N(C=O)O

KP-457 is a selective a disintegrin and metalloproteinase 17 (ADAM17) inhibitor, with higher selectivity for ADAM17 than for other MMPs and ADAM10, and IC50s are 11.1 nM (ADAM17), 748 nM (ADAM10), 717 nM (MMP2), 9760 nM (MMP3), 2200 nM (MMP8), 5410 nM (MMP9), 930 nM (MMP13), 2140 nM (MMP14), and 7100 nM (MMP17), respectively.
KP-457 is a selective metalloproteinase 17 (ADAM17) inhibitor, with higher selectivity for ADAM17 than for other MMPs and ADAM10, and IC50s are 11.1 nM (ADAM17), 748 nM (ADAM10), 717 nM (MMP2), 9760 nM (MMP3), 2200 nM (MMP8), 5410 nM (MMP9), 930 nM (MMP13), 2140 nM (MMP14), and 7100 nM (MMP17), respectively. KP-457 blocks Zn2+ chelation of the catalytic domain of ADAM17. KP-457 (15 μM) retains the expression of GPIbα on iPSC-derived platelets[1].
In a thrombus formation model using immunodeficient mice after platelet transfusion, induced pluripotent stem cells (iPSCs) platelets generated with KP-457 exerts good hemostatic function[1].

Reference

[1]. Hirata S, et al. Selective Inhibition of ADAM17 Efficiently Mediates Glycoprotein Ibα Retention During Ex Vivo Generation of Human Induced Pluripotent Stem Cell-Derived Platelets. Stem Cells Transl Med. 2017 Mar;6(3):720-730.
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