PDBsum entry 4na9

Hydrolase/hydrolase inhibitor

PDB id: 4na9

Contents

Protein chains

254 a.a.

55 a.a.

Ligands

1T7

Metals

_CA

Waters ×177

PDB id:

4na9

Name:

Hydrolase/hydrolase inhibitor

Title:

Factor viia in complex with the inhibitor 3'-amino-5'-[(2s,4r)-6- carbamimidoyl-4-phenyl-1,2,3,4-tetrahydroquinolin-2-yl]biphenyl-2- carboxylic acid

Structure:

Coagulation factor vii heavy chain. Chain: h. Synonym: proconvertin, serum prothrombin conversion accelerator, spca. Engineered: yes. Coagulation factor vii light chain. Chain: l. Synonym: proconvertin, serum prothrombin conversion accelerator, spca.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: f7. Expressed in: cricetinae. Expression_system_taxid: 10026. Expression_system_taxid: 10026

Resolution:

2.24Å R-factor: 0.225 R-free: 0.246

Authors:

A.Wei

Key ref:

M.L.Quan et al. (2014). Tetrahydroquinoline derivatives as potent and selective factor XIa inhibitors. J Med Chem, 57, 955-969. PubMed id: 24405333 DOI: 10.1021/jm401670x

Date:

21-Oct-13 Release date: 12-Feb-14

Protein chain

P08709  (FA7_HUMAN) -  Coagulation factor VII from Homo sapiens

Seq: 466 a.a.

Struc: 254 a.a.

Protein chain

P08709  (FA7_HUMAN) -  Coagulation factor VII from Homo sapiens

Seq: 466 a.a.

Struc: 55 a.a.

Enzyme reactions

• Enzyme class: Chains H, L: E.C.3.4.21.21 - coagulation factor VIIa.
• Reaction: Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.

DOI no: 10.1021/jm401670x

J Med Chem 57:955-969 (2014)

PubMed id: 24405333

Tetrahydroquinoline derivatives as potent and selective factor XIa inhibitors.

M.L.Quan, P.C.Wong, C.Wang, F.Woerner, J.M.Smallheer, F.A.Barbera, J.M.Bozarth, R.L.Brown, M.R.Harpel, J.M.Luettgen, P.E.Morin, T.Peterson, V.Ramamurthy, A.R.Rendina, K.A.Rossi, C.A.Watson, A.Wei, G.Zhang, D.Seiffert, R.R.Wexler.

ABSTRACT

Antithrombotic agents that are inhibitors of factor XIa (FXIa) have the potential to demonstrate robust efficacy with a low bleeding risk profile. Herein, we describe a series of tetrahydroquinoline (THQ) derivatives as FXIa inhibitors. Compound 1 was identified as a potent and selective tool compound for proof of concept studies. It exhibited excellent antithrombotic efficacy in rabbit thrombosis models and did not prolong bleeding times. This demonstrates proof of concept for the FXIa mechanism in animal models with a reversible, small molecule inhibitor.