Withaferin A is one of the most bioactive phytoconstituents of Withania somnifera, a well-known herb in Ayurvedic medical tradition of India. Due to the lactonal steroid's potential to modulate multiple oncogenic pathways, Withaferin A has gained much attention as a possible anti-neoplastic agent. Systematic research on the evaluation of anticancer activities of withaferin A was started around the 1970s. Since then, a large number of studies have demonstrated the ability of withaferin A to suppress the in vivo growth of various human cancer cells’ xenograft tumors as well as experimentally induced carcinogenesis in different rodent models. It has being reported that withaferin-A reduced the growth of human prostate cancer (PC3) cells tumor xenograft in nude mice by blocking the tumor angiogenesis and inducing intratumoral apoptosis. According to this study, i.p. administration of withaferin-A caused regression of implanted tumor cells by decreasing the expression of angiogenesis marker CD31, inducing the expression of proapoptotic protein Bax, and activating caspase-3 via inhibition of nuclear factor-κB (NF-κB) signaling pathway. In a separate study, intratumoral administration of withaferin-A arrested PC3 cells’ xenograft tumor growth in mice by inducing tumor cell death via upregulation of prostate apoptosis response-4 (Par-4). Anticancer activity of withaferin-A has also being demonstrated for gynecological cancer, melanoma, thyroid, gastrointestinal and other types of cancer. Mechanistic basis of the anticancer effects of withaferin-A includes: (1) reinforcement of cellular antioxidant and/or detoxification system; (2) suppression of inflammatory pathways; (3) selective inhibition of tumor cell proliferation and induction of apoptosis; (4) suppression of tumor angiogenesis; (5) blockade of epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastasis; (6) alteration of tumor cell metabolism; (7) immunomodulation; and (8) eradication of cancer stem cells.

Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist. Dihydrexidine was shown to stimulate cyclic AMP synthesis just as well or better than dopamine. It was the first dopamine D1 receptor agonist that had potent antiparkinsonian activity in a primate model of Parkinson's disease. Dihydrexidine produces hypothermia. Dihydrexidine has been shown to alleviate cognitive deficits or enhance cognitive performance in a number of animal models of cognition. It is under investigation for the improving the cognitive and working memory deficits in schizophrenia and schizotypal disorder.

Serabelisib (INK1117 and TAK-117) is an orally bioavailable, PI3K p110α- isoform-specific inhibitor with an in vitro IC50 of 15 nM, highly selective against other isoforms (p110β, p110γ, and p110δ) and mTOR (no significant inhibitions at 1 μM concentration). It displayed significant efficacy in several PI3Kα mutant-specific preclinical mouse xenograft tumor models, and blocked signaling to Akt and inhibited the growth of cancer cells harboring wild-type or mutated p110α. Preclinical studies showed TAK-117 to have the low potential for disrupting glucose metabolism or for causing cardiac adverse events; in rats and monkeys, doses up to 50 mg/kg/day were well tolerated. Serabelisib is currently under clinical evaluation.

Lexithromycin is an early semi-synthetic erythromycin, prepared by reaction of the 9-keto moiety to methyl oxime. Lexithromycin has improved absorption in vivo over erythromycin due to increased hydrophopicity and pH stability. Like all erythromycins, lexithromycin shows broad spectrum antibacterial activity and acts by binding to the 30S and 50S ribosomal sub-units, blocking protein synthesis. Formulations containing lexithromycin were tested in clinical trials as treatment for HIV but were discontinued.

Gestaclone was developed as a progesterone receptor agonist; however, this compound has never been marketed. Information about the current use of this compound is not available.

Trequinsin is a potent PDE3 inhibitor that inhibits PDE4 and PDE2 at higher concentrations. Trequinsin can block platelet aggregation and also inhibit tissue factor expression in human endothelial cells. Trequinsin can enhance cellular cAMP content, forskolin-induced cAMP synthesis, and renin release in cells.

Calanolide A is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) originally extracted from a tropical tree (Calophyllum lanigerum) in the Malaysian rain forest. Viral life-cycle studies indicate that calanolide A acts early in the infection process, similar to the known HIV reverse transcriptase (RT) inhibitor 2', 3'-dideoxycytidine. In enzyme inhibition assays, calanolide A potently and selectively inhibits recombinant HIV type 1 RT but not cellular DNA polymerases or HIV type 2 RT within the concentration range tested. Phase I studies have found that calanolide A is well tolerated. Consequently, it has potential clinical applications in combination with other antiviral drugs to suppress HIV-1 mutants. Nevertheless, the development of calanolide A has been delayed due to its low therapeutic index (range: 16–279), non-ideal antiviral activity, and the complexity of its extraction from plants