5QIM

TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH N-{4-[3-(5-METHOXYPYRIDIN-2-YL)-1H-PYRROLO[3,2-B] PYRIDIN-2-YL]PYRIDIN-2-YL}ACETAMIDE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.188 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.169 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of 4-Azaindole Inhibitors of TGF beta RI as Immuno-oncology Agents.

Zhang, Y.Zhao, Y.Tebben, A.J.Sheriff, S.Ruzanov, M.Fereshteh, M.P.Fan, Y.Lippy, J.Swanson, J.Ho, C.P.Wautlet, B.S.Rose, A.Parrish, K.Yang, Z.Donnell, A.F.Zhang, L.Fink, B.E.Vite, G.D.Augustine-Rauch, K.Fargnoli, J.Borzilleri, R.M.

(2018) ACS Med Chem Lett 9: 1117-1122

  • DOI: https://doi.org/10.1021/acsmedchemlett.8b00357
  • Primary Citation of Related Structures:  
    5QIK, 5QIL, 5QIM, 5QIN

  • PubMed Abstract: 

    The multifunctional cytokine TGFβ plays a central role in regulating antitumor immunity. It has been postulated that inhibition of TGFβ signaling in concert with checkpoint blockade will provide improved and durable immune response against tumors. Herein, we describe a novel series of 4-azaindole TGFβ receptor kinase inhibitors with excellent selectivity for TGFβ receptor 1 kinase. The combination of compound 3f and an antimouse-PD-1 antibody demonstrated significantly improved antitumor efficacy compared to either treatment alone in a murine tumor model.


  • Organizational Affiliation

    Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, New Jersey 08543, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TGF-beta receptor type-1306Homo sapiensMutation(s): 0 
Gene Names: TGFBR1ALK5SKR4
EC: 2.7.11.30
UniProt & NIH Common Fund Data Resources
Find proteins for P36897 (Homo sapiens)
Explore P36897 
Go to UniProtKB:  P36897
PHAROS:  P36897
GTEx:  ENSG00000106799 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP36897
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
J2Y
Query on J2Y

Download Ideal Coordinates CCD File 
B [auth A]N-{4-[3-(5-methoxypyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide
C20 H17 N5 O2
VRPRBQAJAQCSCW-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
C [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
J2Y BindingDB:  5QIM IC50: 6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.188 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.169 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.01α = 90
b = 77.8β = 90
c = 90.27γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
Aimlessdata scaling
AMoREphasing
BUSTERrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2018-10-31 
  • Deposition Author(s): Sheriff, S.

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-31
    Type: Initial release
  • Version 1.1: 2018-12-26
    Changes: Data collection, Database references
  • Version 1.2: 2021-05-12
    Changes: Structure summary
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references