PDBsum entry 3iit

Hydrolase

PDB id: 3iit

Contents

Protein chains

233 a.a. *

54 a.a. *

Ligands

D14

Metals

_CA ×2

Waters ×192

* Residue conservation analysis

PDB id:

3iit

Name:

Hydrolase

Title:

Factor xa in complex with a cis-1,2-diaminocyclohexane derivative

Structure:

Activated factor xa heavy chain. Chain: a. Synonym: coagulation factor x heavy chain, factor x heavy chain. Factor x light chain. Chain: b. Fragment: unp residues 125-178. Synonym: coagulation factor x light chain. Ec: 3.4.21.6

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: proteolytic cleavage product

Resolution:

1.80Å R-factor: 0.203 R-free: 0.233

Authors:

M.Suzuki

Key ref:

K.Yoshikawa et al. (2009). Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part II: exploration of 6-6 fused rings as alternative S1 moieties. Bioorg Med Chem Lett, 17, 8221-8233. PubMed id: 19900814

Date:

03-Aug-09 Release date: 04-Aug-10

Protein chain

P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens

Seq: 488 a.a.

Struc: 233 a.a.

Protein chain

P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens

Seq: 488 a.a.

Struc: 54 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.4.21.6 - coagulation factor Xa.
• Reaction: Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.

Bioorg Med Chem Lett 17:8221-8233 (2009)

PubMed id: 19900814

Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part II: exploration of 6-6 fused rings as alternative S1 moieties.

K.Yoshikawa, S.Kobayashi, Y.Nakamoto, N.Haginoya, S.Komoriya, T.Yoshino, T.Nagata, A.Mochizuki, K.Watanabe, M.Suzuki, H.Kanno, T.Ohta.

ABSTRACT

A series of cis-1,2-diaminocyclohexane derivatives possessing a 6-6 fused ring for the S1 moiety were synthesized as novel factor Xa (fXa) inhibitors. The synthesis, structure-activity relationship (SAR), and physicochemical properties are reported herein, together with the discovery of compound 45c, which has potent anti-fXa activity, good physicochemical properties and pharmacokinetic (PK) profiles, including a reduced negative food effect.