2. Academic Validation
  3. Discovery of a Potent Dual Son of Sevenless 1 (SOS1) and Epidermal Growth Factor Receptor (EGFR) Inhibitor for the Treatment of Prostate Cancer

Discovery of a Potent Dual Son of Sevenless 1 (SOS1) and Epidermal Growth Factor Receptor (EGFR) Inhibitor for the Treatment of Prostate Cancer

  • J Med Chem. 2024 May 9;67(9):7130-7145. doi: 10.1021/acs.jmedchem.3c02433.
Lufeng Zheng 1 2,  Yuxin Zhang 1 2,  Shuang Mei 1,  Tianyuan Xie 1 2,  Yunting Zou 1,  Yuting Wang 1 2,  Han Jing 1 2,  Shengtao Xu 3,  Pierre Dramou 4,  Zhen Xu 5,  Jindong Li 6,  Yang Zhou 7,  Miao-Miao Niu 1
Affiliations

Affiliations

  • 1 Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 211198, China.
  • 2 School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 211198, China.
  • 3 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
  • 4 Department of Analytical Chemistry, School of Sciences, China Pharmaceutical University, Nanjing 210009, China.
  • 5 Department of Pharmacy, Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, China.
  • 6 Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, China.
  • 7 Department of Pathology, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou 213000, China.
PMID: 38630077 DOI: 10.1021/acs.jmedchem.3c02433
Abstract

Multitarget medications represent an appealing therapy against the disease with multifactorial abnormalities─cancer. Therefore, simultaneously targeting son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR), two aberrantly expressed proteins crucial for the oncogenesis and progression of prostate Cancer, may achieve active antitumor effects. Here, we discovered dual SOS1/EGFR-targeting compounds via pharmacophore-based docking screening. The most prominent compound SE-9 exhibited nanomolar inhibition activity against both SOS1 and EGFR and efficiently suppressed the phosphorylation of ERK and Akt in prostate Cancer cells PC-3. Cellular assays also revealed that SE-9 displayed strong antiproliferative activities through diverse mechanisms, such as induction of cell Apoptosis and G1 phase cell cycle arrest, as well as reduction of angiogenesis and migration. Further in vivo findings showed that SE-9 potently inhibited tumor growth in PC-3 xenografts without obvious toxicity. Overall, SE-9 is a novel dual-targeting SOS1/EGFR inhibitor that represents a promising treatment strategy for prostate Cancer.

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