Nelfinavir Mesylate

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Cat Number

API0232163

CAS Number

159989-65-8

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CAS Number

159989-65-8

EINECS

663-870-6

Storage

Store at 2-8°C

Synonyms

Nelfinavir Methanesulfonate; AG1343; Nelfinaviri mesilas; 98D603VP8V; CHEBI:7497; NSC722664; DTXCID601477080

Molecular Formula

C33H49N3O7S2

Molecular Weight

663.9

Smiles

CC1=C(C=CC=C1O)C(=O)N[C@@H](CSC2=CC=CC=C2)[C@@H](CN3C[C@H]4CCCC[C@H]4C[C@H]3C(=O)NC(C)(C)C)O.CS(=O)(=O)O

Appearance

White to off-white amorphous powder

Melting Point

131-135°C

Boiling Point

786.8°C at 760 mmHg

General Description

Nelfinavir mesylate is a peptidomimetic HIV-1 protease inhibitor containing a 2‑methyl‑3‑hydroxybenzoyl group and a thiazole ring. The mesylate salt enhances water solubility. Its structure was rationally designed to mimic the transition state of the viral protease substrate, and it was the first protease inhibitor approved for pediatric use.

Mechanism of Action

Nelfinavir reversibly binds to the active site of HIV-1 protease, preventing cleavage of the viral Gag-Pol polyprotein precursor. This inhibition blocks the maturation of newly formed virions, resulting in the release of non‑infectious, immature viral particles. The drug has high selectivity for HIV-1 protease over human aspartyl proteases and retains activity against some resistant strains.

Application

Nelfinavir is indicated in combination with other antiretrovirals for the treatment of HIV-1 infection in adults and children. It is also investigated for its anticancer properties due to off‑target effects on Akt signaling and the unfolded protein response.

This review summarizes the anti‑cancer mechanisms of nelfinavir and other protease inhibitors. Two main pathways are endoplasmic reticulum stress‑unfolded protein response and Akt inhibition. Additional effects include inhibition of MMP‑2/‑9, downregulation of CDK‑2, VEGF, bFGF, NF‑kB, STAT‑3, HIF‑1α, survivin, androgen receptor, and fatty acid synthase, as well as induction of autophagy and increased radiosensitivity. PIs may be classified as Akt inhibitors, ER stressors, or both. Phase I trials are complete; larger well‑designed trials are needed to establish nelfinavir’s place in cancer therapy.

Fig. 1 A more detailed view of nelfinavir’s action on ER stress. (Koltai T, 2015)

References

Koltai T. Nelfinavir and other protease inhibitors in cancer: mechanisms involved in anticancer activity. F1000Res. 2015;4:9.

In human non‑small cell lung cancer (NSCLC) cell lines and xenograft models, combining nelfinavir (HIV protease inhibitor) with chloroquine (autophagy inhibitor) enhanced endoplasmic reticulum stress, proteotoxicity, and apoptosis compared to either drug alone. The combination significantly inhibited NSCLC cell proliferation in vitro and tumor growth in vivo. Induction of proteotoxicity may represent a promising new target for anticancer drug development.

Fig. 2 Combining nelfinavir (NFV) with chloroquine (CQ) enhances inhibition of non-small cell lung cancer (NSCLC) proliferation and proteotoxicity. (Lopiccolo J, et al., 2021)

References

Lopiccolo J, et al. Combining Nelfinavir With Chloroquine Inhibits In Vivo Growth of Human Lung Cancer Xenograft Tumors. In Vivo. 2021;35(1):141-145.

Does Nelfinavir Mesylate require refrigerated storage as a HIV protease inhibitor?

Yes, it must be stored at 2-8°C. At room temperature, rapid degradation via hydrolysis and oxidation of the phenethyl amide occurs.

Is Nelfinavir Mesylate sensitive to light, and how is this prevented?

Yes, it is photosensitive. Store in light-resistant containers and handle under subdued light to prevent photodegradation of the thiazole ring.

What is the stability of Nelfinavir Mesylate in oral powder or tablet formulations?

When formulated with moisture-protective packaging and stored under refrigeration, stability is maintained for 24 months.

How is the impurity nelfinavir pyridine N-oxide (oxidation product) monitored?

This degradation product is specifically quantified using a stability-indicating HPLC method, ensuring it remains within ICH limits.