12FJ
Crystal structure of 6-fluoropyrazolo[1,5-a]pyridine derivative bound to KIT
This is a non-PDB format compatible entry.
Summary for 12FJ
| Entry DOI | 10.2210/pdb12fj/pdb |
| Descriptor | Mast/stem cell growth factor receptor Kit, ~{N}-[5-(5-cyclopropyl-4~{H}-1,2,4-triazol-3-yl)-4-fluoranyl-2-methyl-phenyl]-6-fluoranyl-pyrazolo[1,5-a]pyridine-3-carboxamide (2 entities in total) |
| Functional Keywords | kit inhibitor, tyrosine kinase inhibitor, inflammation, allergy, chronic urticaria, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 38954.96 |
| Authors | |
| Primary citation | Chen, K.Y.,Qu, S.,Yan, X.,Moon, H.,Lamani, M.,Wang, Z.,Mata, G.,Zhu, J.,Schweickert, P.G.,Sivick, K.E.,Huang, H.T.,Van Abbema, A.M.,Zhao, X.,Green, D.W.,Jin, L.,Young, S.W.,Walters, M.J.,Walker, N.P.,Leleti, M.R.,Powers, J.P.,Jeffrey, J.L. Discovery of a Potent, Orally Bioavailable Small-Molecule Inhibitor of Wildtype KIT with Exceptionally High Kinome Selectivity. J.Med.Chem., 2026 Cited by PubMed Abstract: Mast cells play critical roles in the pathogenesis of many allergic and inflammatory diseases. KIT, a receptor tyrosine kinase, is a crucial regulator of mast cells and, in consequence, the modulation of mast cells through KIT inhibition presents a promising therapeutic approach for treating a range of chronic diseases. Clinical applications of small-molecule KIT inhibitors have been limited to oncology due to adverse effects associated with poor kinome selectivity. Here, we describe a highly selective small-molecule KIT inhibitor () that exhibits excellent broad kinome selectivity, with a selectivity score of S(50%) = 0.003. Data-driven investigations of structure-activity relationships and careful modulation of physicochemical properties yielded improvements in potency, selectivity, and metabolic stability. Compound demonstrated promising therapeutic efficacy in an SCF-driven acute cutaneous anaphylaxis model in rodents. PubMed: 42503832DOI: 10.1021/acs.jmedchem.6c00898 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.629 Å) |
Structure validation
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