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概览

疾病领域	数量

感染	1

排名前五的药物类型	数量

小分子化药	1

排名前五的靶点	数量

env(包膜蛋白)	1

关联

1

项与 Lead Discovery 相关的药物

MAS-596

靶点

env

作用机制

env调节剂

在研机构

Lead Discovery [+2]

原研机构

University of Siena

在研适应症

流感病毒感染

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期-

100 项与 Lead Discovery 相关的临床结果

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0 项与 Lead Discovery 相关的专利（医药）

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7

项与 Lead Discovery 相关的文献（医药）

2025-04-24·Journal of Medicinal Chemistry

Discovery of Naphthyridinone Derivatives as Selective and Potent PKMYT1 Inhibitors with Antitumor Efficacy

Article

作者: Qi, Yunyue ; Qiu, Hongxia ; Liu, Xiaofeng ; Chen, Shuai ; Chen, Bo ; Li, Yi ; Tu, Yifan ; Xu, Zhiheng ; Wu, Jun ; Yang, June ; Yan, Zhipeng ; Tan, Xuefei ; Yang, Juhao ; Shen, Hong C. ; Jiang, Tianyi ; Xu, Jiasu ; Huang, Ke ; Zhu, Sining ; Dey, Fabian ; Zhao, Dan ; Dai, Yu ; Wang, Summer ; Li, Chiho ; Zhu, Wei ; Tang, Yang ; Yao, XiangYu ; Mu, Tong

PKMYT1 is a crucial regulator of the cell cycle, particularly involved in the G2/M transition through the inhibitory phosphorylation of CDK1, and is a promising therapeutic target for cancer therapy. Data mining in the Roche kinome screen database identified a hit characterized by 100% PKMYT1 inhibitory activity at a 10 μM concentration, which was further validated with a PKMYT1 enzymatic assay showing double-digit nanomolar potency. The hit featured a quinolinone central core and a phenol headgroup. The replacement of the problematic phenol headgroup with an indazole moiety induced a flip in the kinase hinge cysteine and glycine residues, resulting in a series of derivatives with enhanced potency, superior kinome selectivity, and no GSH flag. Further structural fine-tuning led to the discovery of compound 36, a novel, selective, and potent PKMYT1 inhibitor with favorable oral pharmacokinetic profiles and promising in vivo antitumor efficacy.

2025-03-04·Proceedings of the National Academy of Sciences

Reply to Trollmann et al.: Perspective on LNP structure and simulation

Article

作者: Rissanen, Sami ; Sun, Jiawei ; Steigemann, Patrick ; Garaizar, Adiran ; Mann, Florian A. ; Zablowsky, Nina ; Díaz-Oviedo, David ; Köbberling, Johannes ; Meier, Katharina ; Steiger, Christoph

2012-02-01·Analytical Biochemistry

Development of a time-resolved fluorescence resonance energy transfer assay for cyclin-dependent kinase 4 and identification of its ATP-noncompetitive inhibitors

Article

作者: Xiao, Shou-Hua ; Ngo, Rachel ; Li, Cong ; Ventura, Manuel ; Emkey, Renee ; Lo, Mei-Chu ; Dai, Kang ; Liang, Lingming ; Lee, Josie ; Eksterowicz, John ; Young, Stephen W.

Protein kinases are recognized as important drug targets due to the pivotal roles they play in human disease. Many kinase inhibitors are ATP competitive, leading to potential problems with poor selectivity and significant loss of potency in vivo due to cellular ATP concentrations being much higher than K(m). Consequently, there has been growing interest in the development of ATP-noncompetitive inhibitors to overcome these problems. There are challenges to identifying ATP-noncompetitive inhibitors from compound library screens because ATP-noncompetitive inhibitors are often weaker and commonly excluded by potency-based hit selection criteria in favor of abundant and highly potent ATP-competitive inhibitors in screening libraries. Here we report the development of a time-resolved fluorescence resonance energy transfer (TR-FRET) assay for protein kinase cyclin-dependent kinase 4 (CDK4) and the identification of ATP-noncompetitive inhibitors by high-throughput screening after employing a strategy to favor this type of inhibitors. We also present kinetic characterization that is consistent with the proposed mode of inhibition.

100 项与 Lead Discovery 相关的药物交易

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100 项与 Lead Discovery 相关的转化医学

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