5QIK image
Deposition Date 2018-08-05
Release Date 2018-10-31
Last Version Date 2026-02-18
Entry Detail
PDB ID:
5QIK
Keywords:
TRANSFERASE/TRANSFERASE INHIBITOR
Title:
TGF-BETA RECEPTOR TYPE 1 KINASE DOMAIN (T204D) IN COMPLEX WITH N-{4-[3-(6-fluoropyridin-3-yl)-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl]pyridin-2-yl}acetamide
Biological Source:
Source Organism(s):
Homo sapiens (Taxon ID: 9606)
Expression System(s):
Spodoptera frugiperda
Method Details:
Experimental Method:
X-RAY DIFFRACTION
Resolution:
1.58 Å
R-Value Free:
0.19
R-Value Work:
0.16
R-Value Observed:
0.16
Space Group:
P 21 21 21
5QIK validation report missing
Macromolecular Entities
Structures with similar UniProt ID
Protein Blast
Polymer Type:polypeptide(L)
Molecule:TGF-beta receptor type-1
Gene (Uniprot):TGFBR1
Mutagens:T204D
Chain IDs:A
Chain Length:307
Number of Molecules:1
Biological Source:Homo sapiens
UniProt ID:P36897 Pfam ID:PF00069 EC:2.7.10.2
Ligand Molecules
GOL
J2M
Primary Citation
Discovery of 4-Azaindole Inhibitors of TGF beta RI as Immuno-oncology Agents.
ACS Med Chem Lett 9 1117 1122 (2018)
PMID: 30429955 DOI: 10.1021/acsmedchemlett.8b00357

Abstact

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.

Legend

Protein

Chemical

Disease

Primary Citation of related structures
5QIK
Feedback Form
Name
Email
Institute
Feedback