3LW0

IGF-1RK in complex with ligand MSC1609119A-1

PDB DOI: https://doi.org/10.2210/pdb3LW0/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): Yes

Deposited: 2010-02-23 Released: 2010-09-29
Deposition Author(s): Graedler, U., Heinrich, T., Boettcher, H., Blaukat, A., Shutes, A., Askew, B.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.79 Å
R-Value Free: 0.185
R-Value Work: 0.157

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Allosteric IGF-1R Inhibitors.

Heinrich, T., Gradler, U., Bottcher, H., Blaukat, A., Shutes, A.

(2010) ACS Med Chem Lett 1: 199-203

PubMed: 24900194 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/ml100044h
Primary Citation of Related Structures:
3LW0

PubMed Abstract:
Targeting allosteric protein sites is a promising approach to interfere selectively with cellular signaling cascades. We have discovered a novel class of allosteric insulin-like growth factor-I receptor (IGF-1R) inhibitors. 3-Cyano-1H-indole-7-carboxylic acid {1-[4-(5-cyano-1H-indol-3-yl)butyl]piperidin-4-yl}amide (10) was found with nanomolar biochemical, micromolar, cellular IGF-1R activity and no relevant interference with cellular insulin receptor signaling up to 30 μM. The allosteric binding site was characterized by X-ray crystallographic studies, and the structural information was used to explain the unique mode of action of this new class of inhibitors.

Organizational Affiliation

Merck Serono, Frankfurter Strasse 250, 64293 Darmstadt, Germany.

Macromolecule Content

Total Structure Weight: 142.33 kDa
Atom Count: 10,929
Modelled Residue Count: 1,168
Deposited Residue Count: 1,216
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Insulin-like growth factor 1 receptor	A, B, C, D	304	Homo sapiens	Mutation(s): 2 Gene Names: IGF1R EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P08069 (Homo sapiens) Explore P08069 Go to UniProtKB: P08069
PHAROS: P08069 GTEx: ENSG00000140443
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P08069
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
CCX Query on CCX Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth B] SDF format, chain H [auth B] SDF format, chain J [auth C] SDF format, chain K [auth C] SDF format, chain M [auth D] SDF format, chain N [auth D] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B] MOL2 format, chain J [auth C] MOL2 format, chain K [auth C] MOL2 format, chain M [auth D] MOL2 format, chain N [auth D]	E [auth A] F [auth A] G [auth B] H [auth B] J [auth C] E [auth A], F [auth A], G [auth B], H [auth B], J [auth C], K [auth C], M [auth D], N [auth D]	3-cyano-N-{1-[4-(5-cyano-1H-indol-3-yl)butyl]piperidin-4-yl}-1H-indole-7-carboxamide C₂₈ H₂₈ N₆ O GVZDPXYOJHKYRC-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain J [auth C] Focus chain K [auth C] Focus chain M [auth D] Focus chain N [auth D] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain J [auth C] Focus chain K [auth C] Focus chain M [auth D] Focus chain N [auth D]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain I [auth B] SDF format, chain L [auth C] MOL2 format, chain I [auth B] MOL2 format, chain L [auth C]	I [auth B], L [auth C]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain I [auth B] Focus chain L [auth C] Interactions & Density Focus chain I [auth B] Focus chain L [auth C]

Binding Affinity Annotations
ID	Source	Binding Affinity
CCX	PDBBind: 3LW0	IC50: 400 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.79 Å
R-Value Free: 0.185
R-Value Work: 0.157
Space Group: H 3

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 189.346	α = 90
b = 189.346	β = 90
c = 115.92	γ = 120

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
XSCALE	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-09-29

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2010-09-29
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2019-12-25
Changes: Advisory, Database references
Version 1.3: 2023-11-01
Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description