3KRL
cFMS Tyrosine kinase in complex with 5-Cyano-furan-2-carboxylic acid [4-(4-methyl-piperazin-1-yl)-2-piperidin-1-yl-phenyl]-amide
Summary for 3KRL
| Entry DOI | 10.2210/pdb3krl/pdb |
| Related | 3KRJ |
| Descriptor | Macrophage colony-stimulating factor 1 receptor, Basic fibroblast growth factor receptor 1, 5-cyano-N-[4-(4-methylpiperazin-1-yl)-2-piperidin-1-ylphenyl]furan-2-carboxamide, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | kinase, inhibitor, chimera, atp-binding, disulfide bond, glycoprotein, immunoglobulin domain, membrane, nucleotide-binding, phosphoprotein, proto-oncogene, receptor, transferase, transmembrane, tyrosine-protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens More |
| Cellular location | Cell membrane; Single-pass type I membrane protein: P07333 |
| Total number of polymer chains | 1 |
| Total formula weight | 38554.02 |
| Authors | Schubert, C. (deposition date: 2009-11-18, release date: 2010-12-01, Last modification date: 2023-09-06) |
| Primary citation | Illig, C.R.,Manthey, C.L.,Wall, M.J.,Meegalla, S.K.,Chen, J.,Wilson, K.J.,Ballentine, S.K.,Desjarlais, R.L.,Schubert, C.,Crysler, C.S.,Chen, Y.,Molloy, C.J.,Chaikin, M.A.,Donatelli, R.R.,Yurkow, E.,Zhou, Z.,Player, M.R.,Tomczuk, B.E. Optimization of a Potent Class of Arylamide Colony-Stimulating Factor-1 Receptor Inhibitors Leading to Anti-inflammatory Clinical Candidate 4-Cyano-N-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1H-imidazole-2-carboxamide (JNJ-28312141). J.Med.Chem., 54:7860-7883, 2011 Cited by PubMed Abstract: A class of potent inhibitors of colony-stimulating factor-1 receptor (CSF-1R or FMS), as exemplified by 8 and 21, was optimized to improve pharmacokinetic and pharmacodynamic properties and potential toxicological liabilities. Early stage absorption, distribution, metabolism, and excretion assays were employed to ensure the incorporation of druglike properties resulting in the selection of several compounds with good activity in a pharmacodynamic screening assay in mice. Further investigation, utilizing the type II collagen-induced arthritis model in mice, culminated in the selection of anti-inflammatory development candidate JNJ-28312141 (23, FMS IC(50) = 0.69 nM, cell assay IC(50) = 2.6 nM). Compound 23 also demonstrated efficacy in rat adjuvant and streptococcal cell wall-induced models of arthritis and has entered phase I clinical trials. PubMed: 22039836DOI: 10.1021/jm200900q PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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