Development of SOS1 targeting molecules as antitumor candidates: design, synthesis, and biological activity evaluations

doi:10.6023/cjoc202605028

Chinese Journal of Organic Chemistry

ARTICLE

靶向SOS1抗肿瘤候选药物的设计、合成与生物活性评价

陈刚胜^a,b, 徐畅^a, 赵雅莉^a, 李双辰^a, 苏熠东^b, 房雷^a,c,*, 苟少华^a,*

^a江苏省生物药物高技术研究重点实验室南京 211189, 中国;
^b江苏豪森药业集团有限公司连云港 222000, 中国;
^c糖化学与生物技术教育部重点实验室（江南大学）

收稿日期:2026-07-26 修回日期:2026-09-07

Development of SOS1 targeting molecules as antitumor candidates: design, synthesis, and biological activity evaluations

Gangsheng Chen^a,b, Chang Xu^a, Yali Zhao^a, Shuangchen Li^a, Yidong Su^b, Lei Fang^a,c,*, Shaohua Gou^a,*

^aSchool of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China;
^bJiangsu Hansoh Pharmaceutical Group CO., LTD., Lianyungang 222000, China;
^cKey Laboratory of Carbohydrate Chemistry and Biotechnology (Jiangnan University), Ministry of Education

Received:2026-07-26 Revised:2026-09-07
Contact: ^*E-mail: sgou@seu.edu.cn (S. Gou); lei.fang@seu.edu.cn (L.Fang)
Supported by:
Priority Academic Program Development of Jiangsu Higher Education Institutions and the National Science and Technology Major Foundation of China.

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Abstract

To identify SOS1 inhibitors, eighteen pyrimido[4,5-b]pyridine derivatives were designed, synthesized and evaluated for their potential antitumor activity. Pharmacological data demonstrated that most of the tested compounds exhibited potent inhibitory activity against SOS1 and could significantly suppress the tumor cells lines harboring the KRAS G12C mutation. Among them, compounds 5a, 5d, 4c, 4d and 4f showed favorable absorption profile in mice. Subsequent assays confirmed that the representative compound 4c also possessed good absorption properties in rats and dogs. Notably, compound 4c exhibited remarkable in vivo antitumor efficacy, which warrants further preclinical pharmacokinetic, safety, and pharmacodynamic evaluations.

Key words: KRAS, SOS1, Pyrimido[4,5-b]pyridine, antitumor, GDP, GTP

Cite this article

Gangsheng Chen, Chang Xu, Yali Zhao, Shuangchen Li, Yidong Su, Lei Fang, Shaohua Gou. Development of SOS1 targeting molecules as antitumor candidates: design, synthesis, and biological activity evaluations[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202605028.

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靶向SOS1抗肿瘤候选药物的设计、合成与生物活性评价

Development of SOS1 targeting molecules as antitumor candidates: design, synthesis, and biological activity evaluations

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