Nelfinavir is a selective, nonpeptidic competitive inhibitor of HIV-1 protease. Nelfinavir shows good in vitro activity against HIV-1 strains[1].
In vitro, Nelfinavir (1, 2.5, 5, 10, 20, 40 and 60µM; 24 and 48h) dose-dependently suppressed proliferation of human A549 cells[2]. Nelfinavir (20μM; 24h) can directly inhibit the activity of aspartic protease DNA damage inducible 1 homolog 2 (DDI2), thereby effectively blocking the proteolysis of NFE2L1 and enhancing the cytotoxicity of proteasome inhibitors (PIs) in cancer cells[3].
In vivo, combining Nelfinavir (50mg/kg/daily; 13 days; i.p.) with Chloroquine inhibits in vivo growth of human lung cancer xenograft tumors[4]. Nelfinavir (100mg/kg per day; 24 days; i.p.) and metformin, when used in combination, act synergistically to inhibit the growth of cervical cancer cell xenografts in nude mice[5].
References:
[1] Perry CM, Frampton JE, McCormack PL, Siddiqui MA, Cvetković RS. Nelfinavir: a review of its use in the management of HIV infection. Drugs. 2005;65(15):2209-44.
[2] He F, Wang G, Xu Z, Huang Z. Nelfinavir restricts A549 cell growth by inhibiting STAT3 signaling. J Int Med Res. 2021 Jun;49(6):3000605211014989.
[3] Gu Y, Wang X, Wang Y, Wang Y, Li J, Yu FX. Nelfinavir inhibits human DDI2 and potentiates cytotoxicity of proteasome inhibitors. Cell Signal. 2020 Nov;75:109775.
[4] Lopiccolo J, Kawabata S, Gills JJ, Dennis PA. Combining Nelfinavir With Chloroquine Inhibits In Vivo Growth of Human Lung Cancer Xenograft Tumors. In Vivo. 2021 Jan-Feb;35(1):141-145.
[5] Xia C, Chen R, Chen J, Qi Q, Pan Y, Du L, Xiao G, Jiang S. Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice. Sci Rep. 2017 Mar 2;7:43373.