Nitroarginine (LNNA), an analog of L-arginine, is a competitive inhibitor of nitric oxide synthase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. The Kd value (k(off)/k(on)) of bovine brain cNOS for LNNA was 15 nM. In contrast to the potent and slow onset of LNNA inhibition of brain cNOS, LNNA inhibition of inducible mouse macrophage NOS (iNOS) was weaker (Ki = 4.4 uM) and rapidly reversible. Thus, LNNA was a 300-fold more potent inhibitor of bovine brain cNOS than mouse macrophage iNOS. By inhibiting nitric oxide synthase LNNA causes the selective reduction of blood flow to tumor cells. Despite the potential of LNNA to function as an adjuvant in cancer therapies, its poor solubility and stability have hindered the development of an injectable formulation of LNNA that is suitable for human administration.

Mevastatin (compactin or ML-236B) is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. This drug induces apoptosis and arrest of cancer cells in G1 phase. Therapeutic effects of mevastatin on serum level of lipoproteins and unbiquinone-10 in patients with familial hypercholesterolemia were investigated. However, that study was discontinued. In addition, mevastatin was investigated for the treatment of melanoma. It was suggested, that mevastatin was unlikely to prevent melanoma at standard doses. However, higher doses could have a role to play in adjuvant therapy by inhibiting growth and invasion of melanoma cells. Also was revealed, that mevastatin increased histone deacetylase inhibitor, LBH589-induced cell death in triple-negative breast cancer (TNBC) cells.