更新于：2024-11-01

CTPS2

更新于：2024-11-01

基本信息

别名

CTP synthase 2、CTP synthetase 2、CTPS2

+ [2]

简介

Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides.

关联

项与 CTPS2 相关的药物

compound 27(Sygnature Discovery)

靶点

CTPS1 x CTPS2

作用机制

CTPS1 modulators [+1]

在研机构

The University of North Carolina at Chapel Hill [+1]

原研机构

Step Pharma SAS初创企业

在研适应症

新型冠状病毒感染 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CTPS1/2 inhibitors(Sygnature Discovery)

靶点

CTPS1 x CTPS2

作用机制

CTPS1拮抗剂 [+1]

在研机构

Sygnature Discovery Ltd.

原研机构

Sygnature Discovery Ltd.

在研适应症

炎症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CTPS2 相关的临床结果

登录后查看更多信息

100 项与 CTPS2 相关的转化医学

登录后查看更多信息

0 项与 CTPS2 相关的专利（医药）

登录后查看更多信息

项与 CTPS2 相关的文献（医药）

2025-12-01·Journal of Clinical Immunology

Concomitant Ultrarare Mutations in TLR3 and CTPS2 in a Patient with Severe and Recurrent Respiratory Infections in Early Life

Letter

作者: Khan, Taushif ; Adeli, Mehdi ; Mackeh, Rafah ; Guennoun, Andrea ; Bougarn, Salim ; Marr, Nico

2024-01-01·Leukemia

CTPS1 is a novel therapeutic target in multiple myeloma which synergizes with inhibition of CHEK1, ATR or WEE1

Article

作者: Zojer, Niklas ; Schreder, Martin ; Pfeiffer, Christina ; Grandits, Alexander M ; Parker, Andrew E ; Schneller, Anja ; Ludwig, Heinz ; Huber, Julia ; Beer, Philip A ; Bolomsky, Arnold ; Asnagli, Hélène

Targeting nucleotide biosynthesis is a proven strategy for the treatment of cancer but is limited by toxicity, reflecting the fundamental nucleotide requirement of dividing cells. The rate limiting step in de novo pyrimidine synthesis is of interest, being catalyzed by two homologous enzymes, CTP synthase 1 (CTPS1) and CTPS2, that could be differentially targeted. Herein, analyses of publicly available datasets identified an essential role for CTPS1 in multiple myeloma (MM), linking high expression of CTPS1 (but not CTPS2) with advanced disease and poor outcomes. In cellular experiments, CTPS1 knockout induced apoptosis of MM cell lines. Exposure of MM cells to STP-B, a novel and highly selective pharmacological inhibitor of CTPS1, inhibited proliferation, induced S phase arrest and led to cell death by apoptosis. Mechanistically, CTPS1 inhibition by STP-B activated DNA damage response (DDR) pathways and induced double-strand DNA breaks which accumulated in early S phase. Combination of STP-B with pharmacological inhibitors of key components of the DDR pathway (ATR, CHEK1 or WEE1) resulted in synergistic growth inhibition and early apoptosis. Taken together, these findings identify CTPS1 as a promising new target in MM, either alone or in combination with DDR pathway inhibition.

2023-09-01·Life Science Alliance

Differential roles of CTP synthetases CTPS1 and CTPS2 in cell proliferation

Article

作者: Laughton, David ; Bourne, Tim ; Beer, Philip ; Martin, Emmanuel ; Minet, Norbert ; Fischer, Alain ; Soudais, Claire ; Lane, Rebecca ; Asnagli, Hélène ; Latour, Sylvain ; Boschat, Anne-Claire

The CTP nucleotide is a key precursor of nucleic acids metabolism essential for DNA replication. De novo CTP production relies on CTP synthetases 1 and 2 (CTPS1 and CTPS2) that catalyze the conversion of UTP into CTP. CTP synthetase activity is high in proliferating cells including cancer cells; however, the respective roles of CTPS1 and CTPS2 in cell proliferation are not known. By inactivation ofCTPS1and/orCTPS2and complementation experiments, we showed that both CTPS1 and CTPS2 are differentially required for cell proliferation. CTPS1 was more efficient in promoting proliferation than CTPS2, in association with a higher intrinsic enzymatic activity that was more resistant to inhibition by 3-deaza-uridine, an UTP analog. The contribution of CTPS2 to cell proliferation was modest when CTPS1 was expressed but essential in absence of CTPS1. Public databases analysis of more than 1,000 inactivated cancer cell lines for CTPS1 or CTPS2 confirmed that cell growth is highly dependent of CTPS1 but less or not of CTPS2. Therefore, our results demonstrate that CTPS1 is the main contributor to cell proliferation.