PDBsum entry 6izn

Transcription

PDB id

6izn

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Contents

			Protein chain

					265 a.a.

			Ligands

					SER-LEU-LEU-LYS- LYS-LEU-LEU-LEU- ALA-PRO


					B1O

			Waters ×159

PDB id:

6izn

Links

Name:

Transcription

Title:

Crystal structure of the ppargamma-lbd complexed with compound 3g

Structure:

Peroxisome proliferator-activated receptor gamma. Chain: a. Synonym: ppar-gamma,nuclear receptor subfamily 1 group c member 3. Engineered: yes. Peptide from peroxisome proliferator-activated receptor gamma coactivator 1-alpha. Chain: c. Synonym: ppargc-1-alpha,ligand effect modulator 6. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pparg, nr1c3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.75Å

R-factor:

0.239

R-free:

0.265

Authors:

Y.Matsui,H.Hanzawa

Key ref:

T.Shinozuka et al. (2019). Structure-Activity Relationship Studies of 3- or 4-Pyridine Derivatives of DS-6930. ACS Med Chem Lett, 10, 358-362. PubMed id: 30891140 DOI: 10.1021/acsmedchemlett.8b00645

Date:

20-Dec-18

Release date:

27-Mar-19

PROCHECK

	Headers

	References

Protein chain

P37231 (PPARG_HUMAN) - Peroxisome proliferator-activated receptor gamma from Homo sapiens

Seq: Struc:					505 a.a. 265 a.a.

Key:

PfamA domain

Secondary structure

DOI no: 10.1021/acsmedchemlett.8b00645	ACS Med Chem Lett 10:358-362 (2019)
PubMed id: 30891140

Structure-Activity Relationship Studies of 3- or 4-Pyridine Derivatives of DS-6930.
T.Shinozuka, T.Tsukada, K.Fujii, E.Tokumaru, Y.Matsui, S.Wakimoto, T.Ogata, K.Araki, R.Sawamura, N.Watanabe, M.Mori, J.Tanaka.

ABSTRACT

Derivatization efforts were continued to discover backups for a potent selective PPARγ modulator, DS-6930. In this Letter, the replacement of 2-pyridine ring in DS-6930 with 3- or 4-pyridyl group is reported. As the introduction of substituents on the pyridine ring did not provide potent partial agonists, modifications of benzimidazole ring were explored to discover potent intermediate agonists. 4'-Alkoxy substituted benzimidazoles failed to show potent efficacy in vivo, whereas 7'-fluoro benzimidazole 3g (DS19161384) was found to result in robust plasma glucose reductions with excellent DMPK profiles.