3dt1

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3dt1, resolution 2.80Å ()
Ligands:
Gene: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2 (Homo sapiens)
Activity: Mitogen-activated protein kinase, with EC number 2.7.11.24
Related: 3ds6
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

P38 Complexed with a quinazoline inhibitor

Publication Abstract from PubMed

Investigations into the structure-activity relationships (SAR) of a series of phthalazine-based inhibitors of p38 are described. These efforts originated from quinazoline 1 and through rational design led to the development of a series of orally bioavailable, potent, and selective inhibitors. Kinase selectivity was achieved by exploiting a collection of interactions with p38alpha including close contact to Ala157, occupation of the hydrophobic gatekeeper pocket, and a residue flip with Gly110. Substitutions on the phthalazine influenced the pharmacokinetic properties, of which compound 16 displayed the most desirable profile. Oral dosing (0.03 mg/kg) of 16 in rats 1 h prior to LPS challenge gave a >50% decrease in TNFalpha production.

Discovery of Highly Selective and Potent p38 Inhibitors Based on a Phthalazine Scaffold., Herberich B, Cao GQ, Chakrabarti PP, Falsey JR, Pettus L, Rzasa RM, Reed AB, Reichelt A, Sham K, Thaman M, Wurz RP, Xu S, Zhang D, Hsieh F, Lee MR, Syed R, Li V, Grosfeld D, Plant MH, Henkle B, Sherman L, Middleton S, Wong LM, Tasker AS, J Med Chem. 2008 Sep 26. PMID:18817365

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3dt1 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Herberich B, Cao GQ, Chakrabarti PP, Falsey JR, Pettus L, Rzasa RM, Reed AB, Reichelt A, Sham K, Thaman M, Wurz RP, Xu S, Zhang D, Hsieh F, Lee MR, Syed R, Li V, Grosfeld D, Plant MH, Henkle B, Sherman L, Middleton S, Wong LM, Tasker AS. Discovery of Highly Selective and Potent p38 Inhibitors Based on a Phthalazine Scaffold. J Med Chem. 2008 Sep 26. PMID:18817365 doi:10.1021/jm8005417

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