7JR8

H-PDGS complexed with a 2-phenylimidazo[1,2-a]pyridine-6-carboxamide inhibitors

PDB DOI: https://doi.org/10.2210/pdb7JR8/pdb

Classification: Isomerase, Transferase/Inhibitor
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2020-08-11 Released: 2021-05-26
Deposition Author(s): Nolte, R.T., Somers, D.O., Gampe, R.T.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.13 Å
R-Value Free: 0.143
R-Value Work: 0.115
R-Value Observed: 0.115

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors.

Schulte, C.A., Deaton, D.N., Diaz, E., Do, Y., Gampe, R.T., Guss, J.H., Hancock, A.P., Hobbs, H., Hodgson, S.T., Holt, J., Jeune, M.R., Kahler, K.M., Kramer, H.F., Le, J., Mortenson, P.N., Musetti, C., Nolte, R.T., Orband-Miller, L.A., Peckham, G.E., Petrov, K.G., Pietrak, B.L., Poole, C., Price, D.J., Saxty, G., Shillings, A., Smalley Jr., T.L., Somers, D.O., Stewart, E.L., Stuart, J.D., Thomson, S.A.

(2021) Bioorg Med Chem Lett 47: 128113-128113

PubMed: 33991628 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2021.128113
Primary Citation of Related Structures:
6ZTC, 7JR6, 7JR8

PubMed Abstract:
Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.

Organizational Affiliation

GlaxoSmithKline, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, NC 27709, United States. Electronic address: [email protected].

Macromolecule Content

Total Structure Weight: 48.56 kDa
Atom Count: 4,279
Modelled Residue Count: 400
Deposited Residue Count: 400
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Hematopoietic prostaglandin D synthase	A, B	200	Homo sapiens	Mutation(s): 0 Gene Names: HPGDS, GSTS, PGDS, PTGDS2 EC: 5.3.99.2 (PDB Primary Data), 2.5.1.18 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for O60760 (Homo sapiens) Explore O60760 Go to UniProtKB: O60760
PHAROS: O60760 GTEx: ENSG00000163106
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O60760
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 6 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
VH7 (Subject of Investigation/LOI) Query on VH7 Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain J [auth B] MOL2 format, chain G [auth A] MOL2 format, chain J [auth B] mmCIF format, chain G [auth A] mmCIF format, chain J [auth B]	G [auth A], J [auth B]	N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-2-phenylimidazo[1,2-a]pyridine-6-carboxamide C₂₃ H₂₇ N₃ O₂ GOQZMCCBUBCPNK-WGSAOQKQSA-N		Interactions Focus chain G [auth A] Focus chain J [auth B] Interactions & Density Focus chain G [auth A] Focus chain J [auth B]
GSH Query on GSH Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B]	F [auth A], I [auth B]	GLUTATHIONE C₁₀ H₁₇ N₃ O₆ S RWSXRVCMGQZWBV-WDSKDSINSA-N		Interactions Focus chain F [auth A] Focus chain I [auth B] Interactions & Density Focus chain F [auth A] Focus chain I [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain H [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B]	D [auth A], E [auth A], H [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain K [auth B] SDF format, chain L [auth B] MOL2 format, chain K [auth B] MOL2 format, chain L [auth B] mmCIF format, chain K [auth B] mmCIF format, chain L [auth B]	K [auth B], L [auth B]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain K [auth B] Focus chain L [auth B] Interactions & Density Focus chain K [auth B] Focus chain L [auth B]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain M [auth B] SDF format, chain N [auth B] SDF format, chain O [auth B] MOL2 format, chain M [auth B] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] mmCIF format, chain M [auth B] mmCIF format, chain N [auth B] mmCIF format, chain O [auth B]	M [auth B], N [auth B], O [auth B]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain M [auth B] Focus chain N [auth B] Focus chain O [auth B] Interactions & Density Focus chain M [auth B] Focus chain N [auth B] Focus chain O [auth B]