5qcm

FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl ~{N}-[4-[[(1~{S})-2-[(~{E})-3-[3-chloranyl-2-fluoranyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]prop-2-enoyl]-3,4-dihydro-1~{H}-isoquinolin-1-yl]carbonylamino]phenyl]carbamate

spinqualitylabelsall models 5qcm, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5qcm is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: BVJ, EDO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease FA11_HUMAN Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:612416; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate. Function FA11_HUMAN Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX. Publication Abstract from PubMed Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Preclinical studies using a variety of approaches to reduce FXIa activity, including direct inhibitors of FXIa, have demonstrated good antithrombotic efficacy without increasing bleeding. Based on this potential, we targeted our efforts at identifying potent inhibitors of FXIa with a focus on discovering an acute antithrombotic agent for use in a hospital setting. Herein we describe the discovery of a potent FXIa clinical candidate, 55 (FXIa Ki = 0.7 nM), with excellent preclinical efficacy in thrombosis models and aqueous solubility suitable for intravenous administration. BMS-962212 is a reversible, direct, and highly selective small molecule inhibitor of FXIa. Discovery of a parenteral small molecule coagulation Factor XIa inhibitor clinical candidate (BMS-962212).,Pinto DJP, Orwat MJ, Smith Ii LM, Quan ML, Lam PYS, Rossi KA, Apedo A, Bozarth JM, Wu Y, Zheng JJ, Xin B, Toussaint N, Stetsko P, Gudmundsson O, Maxwell BD, Crain EJ, Wong PC, Lou Z, Harper TW, Chacko SA, Myers JE, Sheriff S, Zhang H, Hou X, Mathur A, Seiffert DA, Wexler RR, Luettgen JM, Ewing WR J Med Chem. 2017 Oct 27. doi: 10.1021/acs.jmedchem.7b01171. PMID:29077405 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Factor XIa 3D structures

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