GSK-2981278

Cas：1474110-21-8

Product Information：

GSK-2981278 is a highly potent and selective inverse agonist of retinoic acid receptor-related orphan receptor gamma (ROR gamma). GSK2981278 is a strong RORγ-selective inverse agonist that inhibits activation of the il17 promoter. GSK2981278 robustly inhibits RORγ-mediated cytokine production at both the mRNA and protein level. GSK2981278 attenuates inflammation in a mouse model of psoriasis. Topical treatment with GSK2981278 will significantly limit Th17-type cytokine expression and should therefore lead to improved clinical outcomes for patients.

Chemical Formula: C25H35NO5S

Exact Mass: 461.2236

Molecular Weight: 461.62

Elemental Analysis: C, 65.05; H, 7.64; N, 3.03; O, 17.33; S, 6.95

Synonym: 

GSK2981278

GSK-2981278

GSK 2981278

Chemical Name:

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

InChi Key:

LZLBRISQTJVZNP-UHFFFAOYSA-N

InChi Code: 

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

Smiles Code:

O=S(C1=CC=C(OCC2CCOCC2)C(CO)=C1)(N(C3=CC=C(CC)C=C3)CC(C)C)=O

Technical Data：

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

In Vitro：

GSK2981278 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.

GSK2981278 (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 GSK2981278 led to a near-complete inhibition of IL-17A protein secretion.

In Vivo:

GSK2981278 (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. GSK2981278 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.