Drug Repositioning – Nelfinavir (From AntiViral to AntiCancer)

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Drug Repositioning Nelfinavir (From AntiViral to AntiCancer)


Nelfinavir is a competitive inhibitor of human immunodeficiency virus (HIV) aspartyl protease and is being used in combination with other antiretroviral drugs to treat patients with HIV infection. It received the US-FDA approval in 1997 for an oral dose regimen of 750 mg three times daily. It was later modified to a regimen of 1250 mg twice daily as recommended by US-FDA. Both regimens were proven to be equally effective. Nelfinavir is a well-tolerated drug with some common side effects such as insulin resistance, hyperglycemia and lipodystrophy.

Researchers have found potential anticancer activity of nelfinavir. It was reported to inhibit the growths of Kaposi’s sarcoma, multiple myeloma, prostate cancer and breast cancer. Nelfinavir exhibited a broad-spectrum anticancer activity in vivo, being efficacious in several preclinical cancer models.

Recently conducted a Phase I clinical trial of nelfinavir and chemo radiation for locally advanced pancreatic cancer. In this trial, nelfinavir showed potent radio sensitizing and antitumor activities without adding toxicity in patients with pancreatic cancer. Although nelfinavir is known to inhibit AKT signaling pathway, it does not directly inhibit the kinase activity of AKT.


Nelfinavir is known to have a strong anticancer activity through multiple pathways including induction of ER stress, apoptosis and autophagy, and inhibition of AKT pathway and hypoxia-inducible factor 1α (HIF-1α)-dependent angiogenesis. Nelfinavir was shown to inhibit the chymotrypsin- and trypsin-like activities of 20S human proteasome. However, whether anti-proteasome effect is the primary mechanism of nelfinavir for anticancer activity remains elusive since nelfinavir causes proteasome-dependent degradation of several proteins. HSP90 is another proposed molecular target of nelfinavir, of which the inhibition leads to a decrease in the levels of its client proteins including HER2, AKT and CDKs through proteasome-dependent degradation.

Nelfinavir is now under more than 20 Phase I/II clinical trials for cancer. Although the anticancer mechanism of nelfinavir remains to be completely elucidated, promising anticancer activities have been reported from the clinical studies


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