GSK-2981278

GSK-2981278 is a highly potent and selective inverse agonist of retinoic acid receptor-related orphan receptor gamma (ROR gamma). GSK-2981278 is a strong RORγ-selective inverse agonist that inhibits activation of the il17 promoter. GSK-2981278 robustly inhibits RORγ-mediated cytokine production at both the mRNA and protein level. GSK-2981278 attenuates inflammation in a mouse model of psoriasis. Topical treatment with GSK-2981278 will significantly limit Th17-type cytokine expression and should therefore lead to improved clinical outcomes for patients.

Product information

CAS Number: 1474110-21-8

Molecular Weight: 461.61

Formula: C25H35NO5S

Synonym:

GSK 2981278

Chemical Name: N-(4-ethylphenyl)-3-(hydroxymethyl)-N-isobutyl-4-((tetrahydro-2H-pyran-4-yl)methoxy)benzenesulfonamide

Smiles: CC(C)CN(C1=CC=C(CC)C=C1)S(=O)(=O)C1=CC(CO)=C(C=C1)OCC1CCOCC1

InChiKey: LZLBRISQTJVZNP-UHFFFAOYSA-N

InChi: InChI=1S/C25H35NO5S/c1-4-20-5-7-23(8-6-20)26(16-19(2)3)32(28,29)24-9-10-25(22(15-24)17-27)31-18-21-11-13-30-14-12-21/h5-10,15,19,21,27H,4,11-14,16-18H2,1-3H3

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

GSK-2981278 markedly and potently inhibits IL-17A and IL-22 protein secretion in a concentration dependent manner (IC50 = 3.2 nM) during 5 days of culture under Th17 skewing conditions. GSK-2981278 (0.3, 1, 3, 10, 30, 100, 300, 1000 pM; 5 day) potently and selectively inhibits IL-17 and IL-22 levels. Culture in the presence of ≥3 nM GSK-2981278 led to a near-complete inhibition of IL-17A protein secretion.

In Vivo:

GSK-2981278 (1% in ointment; topically; for three days) reduces skin redness and scaling, as well as decreased hyperplasia, as evidenced by a 23% reduction in epidermal thickness. GSK-2981278 attenuates inflammation in a mouse model of psoriasis.

References:

1. Smith SH, Peredo CE, Takeda Y, Bui T, Neil J, Rickard D, Millerman E, Therrien JP, Nicodeme E, Brusq JM, Birault V, Viviani F, Hofland H, Jetten AM, Cote-Sierra J. Development of a Topical Treatment for Psoriasis Targeting RORγ: From Bench to Skin. PLoS One. 2016 Feb 12;11(2):e0147979. doi: 10.1371/journal.pone.0147979. PubMed PMID: 26870941; PubMed Central PMCID: PMC4752338.

Products are for research use only. Not for human use.