PDBsum entry 5imx

Transferase/transferase inhibitor

PDB id: 5imx

Contents

Protein chain

266 a.a.

Ligands

CZ4

Waters ×30

PDB id:

5imx

Name:

Transferase/transferase inhibitor

Title:

Anaplastic lymphoma kinase (alk) catalytic domain complexed with novel inhibitor 3-sulfonylpyrazol-4-amino pyrimidine

Structure:

Alk tyrosine kinase receptor. Chain: a. Fragment: unp residues 1093-1411. Synonym: anaplastic lymphoma kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: alk. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.12Å R-factor: 0.213 R-free: 0.259

Authors:

C.Wang,P.Zhang,J.Dong

Key ref:

P.Zhang et al. (2016). Design and synthesis of novel 3-sulfonylpyrazol-4-amino pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors. Bioorg Med Chem Lett, 26, 1910-1918. PubMed id: 26979157 DOI: 10.1016/j.bmcl.2016.03.017

Date:

07-Mar-16 Release date: 04-May-16

Protein chain

Q9UM73  (ALK_HUMAN) -  ALK tyrosine kinase receptor from Homo sapiens

Seq: 1620 a.a.

Struc: 266 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.bmcl.2016.03.017

Bioorg Med Chem Lett 26:1910-1918 (2016)

PubMed id: 26979157

Design and synthesis of novel 3-sulfonylpyrazol-4-amino pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors.

P.Zhang, J.Dong, B.Zhong, D.Zhang, H.Yuan, C.Jin, X.Xu, H.Li, Y.Zhou, Z.Liang, M.Ji, T.Xu, G.Song, L.Zhang, G.Chen, X.Meng, D.Sun, J.Shih, R.Zhang, G.Hou, C.Wang, Y.Jin, Q.Yang.

ABSTRACT

Anaplastic lymphoma kinase (ALK) is a highly attractive therapeutic target for the treatment of some non-small cell lung cancer patients. This Letter describes the further SAR exploration on the novel 3-sulfonylpyrazol-4-amino pyrimidine scaffold. This work identified a compound 53 with very good in vitro/in vivo efficacies, good DMPK properties together with better hERG tolerability and it is currently being profiled for the evaluation as a potential pre-clinical candidate.