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S18-000003 Sale

目录号 : GC65155

S18-000003, a potent, selective and orally active inhibitor of retinoic acid receptor-related orphan receptor-gamma-t (RORγt), with an IC50 of <30 μM towards human RORγt in competitive binding assays.

S18-000003 Chemical Structure

Cas No.:2068119-11-7

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥2,673.00
现货
5mg
¥2,340.00
现货
10mg
¥3,780.00
现货
25mg
¥7,560.00
现货
50mg
¥12,150.00
现货

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Sample solution is provided at 25 µL, 10mM.

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实验参考方法

RORγt

<30nM(IC50)

产品描述

S18-000003, a potent, selective and orally active inhibitor of retinoic acid receptor-related orphan receptor-gamma-t (RORγt), with an IC50 of <30 μM towards human RORγt in competitive binding assays.

S18-000003 is a potent, selective and orally active inhibitor of retinoic acid receptor-related orphan receptor-gamma-t (RORγt).[1]

[1] Sasaki Y, et al. Bioorg Med Chem Lett. 2018 Dec 1;28(22):3549-3553.

Chemical Properties

Cas No. 2068119-11-7 SDF Download SDF
分子式 C26H25F3N2O4S 分子量 518.55
溶解度 DMSO : 100 mg/mL (192.85 mM; Need ultrasonic) 储存条件 Store at -20°C
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溶解性数据

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1 mg 5 mg 10 mg
1 mM 1.9285 mL 9.6423 mL 19.2845 mL
5 mM 0.3857 mL 1.9285 mL 3.8569 mL
10 mM 0.1928 mL 0.9642 mL 1.9285 mL
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Research Update

Discovery of a potent orally bioavailable retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitor, S18-000003

Bioorg Med Chem Lett 2018 Dec 1;28(22):3549-3553.PMID:30301676DOI:10.1016/j.bmcl.2018.09.032.

The retinoic acid receptor-related orphan receptor-gamma-t (RORγt) is the master transcription factor responsible for regulating the development and function of T-helper 17 (Th17) cells, which are related to the pathology of several autoimmune disorders. Therefore, RORγt is an attractive drug target for such Th17-mediated autoimmune diseases. A structure-activity relationship (SAR) study of lead compound 1 yielded a novel series of RORγt inhibitors, represented by compound 6. Detailed SAR optimization, informed by X-ray cocrystal structure analysis, led to the discovery of a potent orally bioavailable RORγt inhibitor 25, which inhibited IL-17 production in the skin of IL-23-treated mice by oral administration.

A novel RORγt inhibitor is a potential therapeutic agent for the topical treatment of psoriasis with low risk of thymic aberrations

J Dermatol Sci 2019 Mar;93(3):176-185.PMID:30905492DOI:10.1016/j.jdermsci.2019.03.002.

Background: Retinoic acid receptor-related orphan receptor gamma t (RORγt) has critical roles in the development, maintenance and function of interleukin (IL)-17-producing cells and is a highly attractive target for the treatment of IL-17-mediated autoimmune disease, particularly psoriasis. On the other hand, RORγt is also critical for controlling apoptosis during thymopoiesis, and genetic RORγt ablation or systematic RORγt inhibition cause progressive thymic aberrations leading to T cell lymphomas. Objective: We investigated whether topical administration of our novel RORγt inhibitor, S18-000003 has therapeutic potential for psoriasis with low risk of thymic aberrations. Methods: We evaluated the effect of topical S18-000003 on psoriasis-like skin inflammation and influence on the thymus in a 12-O-tetradecanoylphorbol-13-acetate-induced K14.Stat3C mouse psoriasis model. Results: S18-000003 markedly inhibited the development of psoriatic skin inflammation via suppression of the IL-17 pathway. In the skin, S18-000003 suppressed all subsets of IL-17-producing cells that we previously identified in this psoriasis model: Th17 cells, Tc17 cells, dermal γδ T cells, TCR- cells that probably included innate lymphoid cells, and CD4-CD8- double-negative αβ T cells. Notably, neither reduction of CD4+CD8+ double-positive thymocytes nor dysregulation of cell cycling was observed in S18-000003-treated mice, even at a high dose. Conclusion: Our topically administered RORγt inhibitor is a potential therapeutic agent for psoriasis with low risk of thymic lymphoma.