3KCK

A Novel Chemotype of Kinase Inhibitors

PDB DOI: https://doi.org/10.2210/pdb3KCK/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2009-10-21 Released: 2009-11-24
Deposition Author(s): Zuccola, H.J., Wang, T., Ledeboer, M.W.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.20 Å
R-Value Free: 0.296
R-Value Work: 0.225
R-Value Observed: 0.244

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

A novel chemotype of kinase inhibitors: Discovery of 3,4-ring fused 7-azaindoles and deazapurines as potent JAK2 inhibitors.

Wang, T., Ledeboer, M.W., Duffy, J.P., Pierce, A.C., Zuccola, H.J., Block, E., Shlyakter, D., Hogan, J.K., Bennani, Y.L.

(2010) Bioorg Med Chem Lett 20: 153-156

PubMed: 19945871 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2009.11.021
Primary Citation of Related Structures:
3KCK

PubMed Abstract:
Pictet-Spengler condensation of aldehydes or alpha-keto-esters with 4-(2-anilinophenyl)-7-azaindole (11) or deazapurine (12) gave high yields of the 3,4-fused cyclic compounds. SAR studies, by varying the substituted benzaldehyde components, lead to the discovery of a series of potent JAK2 kinase inhibitors.

Organizational Affiliation

Vertex Pharmaceuticals Inc., 130 Waverly St., Cambridge, MA 02139-4242, United States. tiansheng_wang@vrtx.com

Macromolecule Content

Total Structure Weight: 37.13 kDa
Atom Count: 2,506
Modelled Residue Count: 287
Deposited Residue Count: 313
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Tyrosine-protein kinase JAK2	A	313	Homo sapiens	Mutation(s): 0 Gene Names: JAK2 EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for O60674 (Homo sapiens) Explore O60674 Go to UniProtKB: O60674
PHAROS: O60674 GTEx: ENSG00000096968
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O60674
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
3KC Query on 3KC Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	3-chloro-4-(4H-3,4,7-triazadibenzo[cd,f]azulen-6-yl)phenol C₂₀ H₁₂ Cl N₃ O JBHMPWHPXOOFNL-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
PTR Query on PTR	A	L-PEPTIDE LINKING	C₉ H₁₂ N O₆ P		TYR

Binding Affinity Annotations
ID	Source	Binding Affinity
3KC	PDBBind: 3KCK	Ki: 0.8 (nM) from 1 assay(s)
3KC	Binding MOAD: 3KCK	Ki: 0.8 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.20 Å
R-Value Free: 0.296
R-Value Work: 0.225
R-Value Observed: 0.244
Space Group: C 2 2 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 95.156	α = 90
b = 100.803	β = 90
c = 67.621	γ = 90

Software Package:

Software Name	Purpose
d*TREK	data scaling
REFMAC	refinement
PDB_EXTRACT	data extraction
BOS	data collection
d*TREK	data reduction
REFMAC	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-11-24

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2009-11-24
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.