GSK2981278 | CAS#1474110-21-8 | ROR Gamma

GSK2981278
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 526931

CAS#: 1474110-21-8

Description: GSK2981278 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 Structure

GSK2981278

CAS# 1474110-21-8

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 526931
Name: GSK2981278
CAS#: 1474110-21-8
Chemical Formula: C25H35NO5S
Exact Mass: 461.22
Molecular Weight: 461.620
Elemental Analysis: C, 65.05; H, 7.64; N, 3.03; O, 17.33; S, 6.95

Price and Availability

Size	Price	Availability
10mg	USD 90	Ready to ship
25mg	USD 190	Ready to ship
50mg	USD 350	Ready to ship
100mg	USD 550	Ready to ship
200mg	USD 950	Ready to ship
500mg	USD 1850	Ready to ship
1g	USD 2950	Ready to ship
2g	USD 4850	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: GSK2981278; GSK-2981278; GSK 2981278.

IUPAC/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

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

More Info:

Product Data:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#A9T02K21

QC Data:

View QC data: current batch, Lot#A9T02K21

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	GSK2981278 is a highly potent and selective inverse agonist for RORγ.
In vitro activity:	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. Reference: PLoS One. 2016 Feb 12;11(2):e0147979. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26870941/
In vivo activity:	The imiquimod (IMQ) mouse model was employed to demonstrate efficacy of GSK2981278 in a psoriaform-like mouse model. Topical application of IMQ can induce and exacerbate psoriasis-like chronic skin inflammation in mice, including epidermal thickening, a dependence on T cell immunity, and a mechanism dependent on the IL-23/IL-17 pathway. It was first confirmed that GSK2981278 can inhibit IL-17A protein secretion by mouse CD4+ T cells, confirming cross-reactivity of our compound for both mouse and human RORγ (data not shown). Next, mice were treated topically with GSK2981278 (1% ointment or placebo) for three days (day -3 to day 0), after which mice continued to receive compound for the duration of the study. Starting on day 0, mice were challenged topically with IMQ (5%) cream or petrolatum (non-inflammatory inert cream) for up to ten days (day 0 to day +9). On the last day of treatment, the skin was imaged and clinically assessed. GSK2981278 was undetectable (<5 ng/ml) in serum at harvest, indicating that systemic exposure was minimal. Mice exposed to GSK2981278 exhibited reduced skin redness and scaling, as well as decreased hyperplasia, as evidenced by a 23% reduction in epidermal thickness when compared to the placebo + IMQ-treated group (Fig 2A and 2B). Reference: PLoS One. 2016 Feb 12;11(2):e0147979. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26870941/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	92.0	199.30
	Ethanol	92.0	199.30

Preparing Stock Solutions

The following data is based on the product molecular weight 461.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:
In vitro protocol:	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. PMID: 26870941; PMCID: PMC4752338.
In vivo protocol:	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. PMID: 26870941; PMCID: PMC4752338.

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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.

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