4K1L

Deposited: 2013-04-05 Released: 2014-04-09
Deposition Author(s): Loenze, P., Schimanski-Breves, S., Von der Heyden, C., Engel, C.K.

Experimental Data Snapshot

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

(2013) Bioorg Med Chem Lett 23: 4685-4691

PubMed Abstract:
Racemic cis-1,1-dioxo-5,6-dihydro-[4,1,2]oxathiazine derivative 4a was isolated as an impurity in a sample of a hit from a HTS campaign on 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). After separation by chiral chromatography the 4a-S, 8a-R enantiomer of compound 4a was identified as the true, potent enzyme inhibitor. The cocrystal structure of 4a with human and murine 11ß-HSD1 revealed the unique binding mode of the oxathiazine series. SAR elucidation and optimization in regard to metabolic stability led to monocyclic tetramethyloxathiazines as exemplified by compound 21g.

Organizational Affiliation

Sanofi Deutschland GmbH, R&D, Industriepark Höchst, 65926 Frankfurt am Main, Germany.

Macromolecule Content

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Corticosteroid 11-beta-dehydrogenase isozyme 1	A, B, C, D	286	Homo sapiens	Mutation(s): 1 Gene Names: HSD11B1, HSD11, HSD11L EC: 1.1.1.146
UniProt & NIH Common Fund Data Resources
Find proteins for P28845 (Homo sapiens) Explore P28845 Go to UniProtKB: P28845
PHAROS: P28845 GTEx: ENSG00000117594
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P28845
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NDP Query on NDP Download Ideal Coordinates CCD File SDF format, chain J [auth C] SDF format, chain L [auth D] SDF format, chain F [auth A] SDF format, chain H [auth B] MOL2 format, chain J [auth C] MOL2 format, chain L [auth D] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B]	F [auth A], H [auth B], J [auth C], L [auth D]	NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE C₂₁ H₃₀ N₇ O₁₇ P₃ ACFIXJIJDZMPPO-NNYOXOHSSA-N		Interactions Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D] Interactions & Density Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain L [auth D]
SFF Query on SFF Download Ideal Coordinates CCD File SDF format, chain G [auth B] SDF format, chain I [auth C] SDF format, chain E [auth A] SDF format, chain K [auth D] MOL2 format, chain G [auth B] MOL2 format, chain I [auth C] MOL2 format, chain E [auth A] MOL2 format, chain K [auth D]	E [auth A], G [auth B], I [auth C], K [auth D]	(4aS,8aR)-N-cyclohexyl-4a,5,6,7,8,8a-hexahydro-4,1,2-benzoxathiazin-3-amine 1,1-dioxide C₁₃ H₂₂ N₂ O₃ S ZMDVQNCMHSXAPA-NWDGAFQWSA-N		Interactions Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Focus chain K [auth D] Interactions & Density Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Focus chain K [auth D]

Binding Affinity Annotations
ID	Source	Binding Affinity
SFF	Binding MOAD: 4K1L	IC50: 31 (nM) from 1 assay(s)

Experimental Data & Validation

Unit Cell:

Software Package:

Entry History

Deposition Author(s):

Loenze, P.

Version 1.0: 2014-04-09
Type: Initial release
Version 1.1: 2023-09-20
Changes: Data collection, Database references, Derived calculations, Refinement description