LSN 3213128(LSN 3213128) - 药物靶点：AICARFT_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

AICARFT

作用机制

AICARFT抑制剂(AICAR甲酰基转移酶抑制剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病

在研适应症-

非在研适应症

三阴性乳腺癌

原研机构

Lilly Research Laboratories

在研机构-

非在研机构

Lilly Research Laboratories

最高研发阶段无进展临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C17H16FN3O4S2

InChIKeyDSUZLJDXUJUTGI-LLVKDONJSA-N

CAS号1941211-99-9

关联

100 项与 LSN 3213128 相关的临床结果

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100 项与 LSN 3213128 相关的转化医学

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100 项与 LSN 3213128 相关的专利（医药）

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1

项与 LSN 3213128 相关的文献（医药）

Scientific Reports3区 · 综合性期刊

Characterization of a novel AICARFT inhibitor which potently elevates ZMP and has anti-tumor activity in murine models

3区 · 综合性期刊

ArticleOA

作者: Njoroge, F George ; Iversen, Philip W ; Durham, Timothy B ; Thrasher, Kenneth J ; Fales, Kevin R ; Roth, Kenneth D ; Wang, Tao ; Hui, Yu-Hua ; Frimpong, Kwame ; Wu, Zhipei ; Lee, Matthew R ; Geeganage, Sandaruwan ; Dally, Robert D ; Shepherd, Timothy A ; Spencer, Charles D ; Thibodeaux, Stefan ; Mc Cowan, Jefferson R ; Wang, Yong ; Torrado, Alicia ; Luo, Shuang ; Meier, Timothy I ; Qian, Yue-Wei ; Toth, James L ; Konicek, Susan A ; Foreman, Robert T ; Brooks, Harold B ; Si, Chong

AbstractAICARFT is a folate dependent catalytic site within the ATIC gene, part of the purine biosynthetic pathway, a pathway frequently upregulated in cancers. LSN3213128 is a potent (16 nM) anti-folate inhibitor of AICARFT and selective relative to TS, SHMT1, MTHFD1, MTHFD2 and MTHFD2L. Increases in ZMP, accompanied by activation of AMPK and cell growth inhibition, were observed with treatment of LY3213128. These effects on ZMP and proliferation were dependent on folate levels. In human breast MDA-MB-231met2 and lung NCI-H460 cell lines, growth inhibition was rescued by hypoxanthine, but not in the A9 murine cell line which is deficient in purine salvage. In athymic nude mice, LSN3213128 robustly elevates ZMP in MDA-MB-231met2, NCI-H460 and A9 tumors in a time and dose dependent manner. Significant tumor growth inhibition in human breast MDA-MB231met2 and lung NCI-H460 xenografts and in the syngeneic A9 tumor model were observed with oral administration of LSN3213128. Strikingly, AMPK appeared activated within the tumors and did not change even at high levels of intratumoral ZMP after weeks of dosing. These results support the evaluation of LSN3213128 as an antineoplastic agent.

100 项与 LSN 3213128 相关的药物交易

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