TPT-004(TPT-004) - 药物靶点：TPH1_在研适应症：结直肠癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

TPH1

作用机制

TPH1抑制剂(色氨酸羟化酶1抑制剂)

治疗领域

肿瘤消化系统疾病

在研适应症

结直肠癌

非在研适应症-

原研机构-

在研机构-

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C18H20N6O3S

InChIKeyFJDRFUYWOVFIPP-UHFFFAOYSA-N

CAS号3032648-15-7

关联

100 项与 TPT-004 相关的临床结果

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100 项与 TPT-004 相关的转化医学

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100 项与 TPT-004 相关的专利（医药）

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1

项与 TPT-004 相关的文献（医药）

2023-11-09·Journal of Medicinal Chemistry1区 · 医学

Structure-Based Design of Xanthine-Imidazopyridines and -Imidazothiazoles as Highly Potent and In Vivo Efficacious Tryptophan Hydroxylase Inhibitors

1区 · 医学

Article

作者: Winkler, Lars ; Bader, Michael ; Wasinska-Kalwa, Malgorzata ; Nazaré, Marc ; Schütz, Anja ; Specker, Edgar ; Oder, Andreas ; von Kries, Jens Peter ; Pleimes, Dirk ; Wesolowski, Radoslaw ; Alenina, Natalia ; Heinemann, Udo ; Mallow, Keven ; Matthes, Susann

Tryptophan hydroxylases catalyze the first and rate-limiting step in the biosynthesis of serotonin, a well-known neurotransmitter that plays an important role in multiple physiological functions. A reduction of serotonin levels, especially in the brain, can cause dysregulation leading to depression or insomnia. In contrast, overproduction of peripheral serotonin is associated with symptoms like carcinoid syndrome and pulmonary arterial hypertension. Recently, we developed a class of TPH inhibitors based on xanthine-benzimidazoles, characterized by a tripartite-binding mode spanning the binding sites of the cosubstrate pterin and the substrate tryptophan and by chelation of the catalytic iron ion. Herein, we describe the structure-based development of a second generation of xanthine-imidiazopyridines and -imidazothiazoles designed to inhibit TPH1 in the periphery while preventing the interaction with TPH2 in the brain. Lead compound 32 (TPT-004) shows superior pharmacokinetic and pharmacodynamic properties as well as efficacy in preclinical models of peripheral serotonin attenuation and colorectal tumor growth.

100 项与 TPT-004 相关的药物交易

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