PDBsum entry 3io7

Transferase

PDB id: 3io7

Contents

Protein chain

284 a.a. *

Ligands

1P5

Waters ×36

* Residue conservation analysis

PDB id:

3io7

Name:

Transferase

Title:

2-aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of jak2

Structure:

Tyrosine-protein kinase jak2. Chain: a. Fragment: jak kinase domain(unp residue 842-1132). Synonym: janus kinase 2, jak-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: jak2. Expressed in: baculovirus. Expression_system_taxid: 10469.

Resolution:

2.60Å R-factor: 0.206 R-free: 0.294

Authors:

H.J.Zuccola,M.W.Ledeboer,A.C.Pierce

Key ref:

M.W.Ledeboer et al. (2009). 2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2. Bioorg Med Chem Lett, 19, 6529-6533. PubMed id: 19857967

Date:

13-Aug-09 Release date: 10-Nov-09

Protein chain

O60674  (JAK2_HUMAN) -  Tyrosine-protein kinase JAK2 from Homo sapiens

Seq: 1132 a.a.

Struc: 284 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.2 - non-specific 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

Bioorg Med Chem Lett 19:6529-6533 (2009)

PubMed id: 19857967

2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2.

M.W.Ledeboer, A.C.Pierce, J.P.Duffy, H.Gao, D.Messersmith, F.G.Salituro, S.Nanthakumar, J.Come, H.J.Zuccola, L.Swenson, D.Shlyakter, S.Mahajan, T.Hoock, B.Fan, W.J.Tsai, E.Kolaczkowski, S.Carrier, J.K.Hogan, R.Zessis, S.Pazhanisamy, Y.L.Bennani.

ABSTRACT

Constitutive activation of the EPO/JAK2 signaling cascade has recently been implicated in a variety of myeloproliferative disorders including polycythemia vera, essential thrombocythemia and myelofibrosis. In an effort to uncover therapeutic potential of blocking the EPO/JAK2 signaling cascade, we sought to discover selective inhibitors that block the kinase activity of JAK2. Herein, we describe the discovery and structure based optimization of a novel series of 2-amino-pyrazolo[1,5-a]pyrimidines that exhibit potent inhibition of JAK2.