6F1X

Complex between MTH1 and compound 7 (a 7-azaindole-2-amide derivative)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design.

Rahm, F.Viklund, J.Tresaugues, L.Ellermann, M.Giese, A.Ericsson, U.Forsblom, R.Ginman, T.Gunther, J.Hallberg, K.Lindstrom, J.Persson, L.B.Silvander, C.Talagas, A.Diaz-Saez, L.Fedorov, O.Huber, K.V.M.Panagakou, I.Siejka, P.Gorjanacz, M.Bauser, M.Andersson, M.

(2018) J Med Chem 61: 2533-2551

  • DOI: https://doi.org/10.1021/acs.jmedchem.7b01884
  • Primary Citation of Related Structures:  
    6F1X, 6F20, 6F22, 6F23

  • PubMed Abstract: 

    Recent literature has both suggested and questioned MTH1 as a novel cancer target. BAY-707 was just published as a target validation small molecule probe for assessing the effects of pharmacological inhibition of MTH1 on tumor cell survival, both in vitro and in vivo. (1) In this report, we describe the medicinal chemistry program creating BAY-707, where fragment-based methods were used to develop a series of highly potent and selective MTH1 inhibitors. Using structure-based drug design and rational medicinal chemistry approaches, the potency was increased over 10,000 times from the fragment starting point while maintaining high ligand efficiency and drug-like properties.


  • Organizational Affiliation

    Sprint Bioscience AB, Novum , 14157 Huddinge , Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
7,8-dihydro-8-oxoguanine triphosphatase
A, B
159Homo sapiensMutation(s): 0 
Gene Names: NUDT1MTH1
EC: 3.6.1.55 (PDB Primary Data), 3.6.1.56 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P36639 (Homo sapiens)
Explore P36639 
Go to UniProtKB:  P36639
PHAROS:  P36639
GTEx:  ENSG00000106268 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP36639
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
C9Q
Query on C9Q

Download Ideal Coordinates CCD File 
C [auth A],
G [auth B]
4-(3-chlorophenyl)-~{N}-ethyl-1~{H}-pyrrolo[2,3-b]pyridine-2-carboxamide
C16 H14 Cl N3 O
AWWOSFPXOHAONT-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
H [auth B]
I [auth B]
D [auth A],
E [auth A],
F [auth A],
H [auth B],
I [auth B],
J [auth B],
K [auth B],
L [auth B],
M [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
C9Q BindingDB:  6F1X IC50: 20 (nM) from 1 assay(s)
Binding MOAD:  6F1X IC50: 20 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.38α = 90
b = 67.27β = 90
c = 82.29γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2018-03-07
    Type: Initial release
  • Version 1.1: 2018-04-04
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-17
    Changes: Data collection, Database references, Refinement description