SAR studies toward discovery of emvododstat (PTC299), a potent dihydroorotate dehydrogenase (DHODH) inhibitor,European Journal of Medicinal Chemistry

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SAR studies toward discovery of emvododstat (PTC299), a potent dihydroorotate dehydrogenase (DHODH) inhibitor
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2022-10-05 , DOI: 10.1016/j.ejmech.2022.114826
Ramil Y Baiazitov ₁ , Hongyan Qi , Tamil Arasu ₂ , William Lennox ₃ , Liangxian Cao ₁ , Marla Weetall ₁ , Bansri Furia ₄ , Jin Zhuo ₄ , Soongyu Choi ₅ , Min Jung Kim ₁ , Josephine Sheedy ₁ , Thomas Davis ₆ , Young-Choon Moon ₁

Affiliation

Dihydroorotate dehydrogenase (DHODH) is the enzyme that catalyzes a rate-determining step during the de novo synthesis of uridine, an important source of cellular pyrimidine nucleotides. Ability to modulate the activity of this enzyme may be used to control diseases associated with rapid, out-of-control cell growth in oncology, immunology, and virology. Emvododstat (PTC299) is a tetrahydro-β-carboline DHODH inhibitor discovered through the GEMS technology (Gene Expression Modulation by Small-Molecules). Described in this paper is the lead optimization campaign that culminated in the discovery of this highly potent DHODH inhibitor.

中文翻译：

SAR 研究发现 emvododstat (PTC299)，一种有效的二氢乳清酸脱氢酶 (DHODH) 抑制剂

二氢乳清酸脱氢酶 (DHODH) 是催化尿苷从头合成过程中决定速率步骤的酶，尿苷是细胞嘧啶核苷酸的重要来源。调节这种酶活性的能力可用于控制与肿瘤学、免疫学和病毒学中快速、失控的细胞生长相关的疾病。Emvododstat (PTC299) 是一种四氢-β-咔啉 DHODH 抑制剂，通过 GEMS 技术（S mall -Molecules 的Gene E xpression M odulation ）发现。本文描述的是领先的优化活动，最终发现了这种高效的 DHODH 抑制剂。

更新日期：2022-10-05

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