MG16

MG16 is a prodrug of 10-Methoxycamptothecin. It functions by downregulating CDK6 and upregulating ASK1 expression. MG16 can induce cell cycle arrest and apoptosis (Apoptosis). Furthermore, it exhibits anticancer activity against Lewis lung carcinoma, small cell lung cancer, and non-small cell lung cancer.

MG16 exhibits potent inhibitory effects on the proliferation of lung cancer cells LLC, A549, and H446 in vitro over 48 hours, with IC50 values of 408.2 ± 32.4 nM, 613.1 ± 54.7 nM, and 140.4 ± 10.4 nM, respectively. MG16 (0.1-100 nM; 48 h) induces dose-dependent apoptosis in A549 and H446 lung cancer cells, demonstrating a significantly stronger pro-apoptotic activity compared to SN-38. Furthermore, MG16 modulates the expression of key apoptotic proteins in A549 (90.1-1 μM) and H446 (10-100 nM) cancer cells, leading to marked activation of Caspase-3 after 24 hours of treatment, which surpasses the Caspase-3 activation observed with SN-38. Additionally, treatment of A549 lung cancer cells with MG16 at its IC50 concentration (613.1 nM) for 48 hours results in cell cycle arrest at the G0/G1 phase.

Administered intravenously at a dosage of 5 mg/kg every other day, MG16 demonstrates significant anti-tumor efficacy, achieving a 75.11% tumor inhibition rate in the murine LLC subcutaneous tumor model. It further exhibits potent lung cancer growth suppression in the murine A549 subcutaneous tumor model, reaching an 80.5% tumor inhibition rate.