Neoandrographolide, one of the principal diterpene lactones, isolated from a medicinal herb Andrographis paniculata Nees. Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae), also known as “kalmegh” in India, is a widely distributed plant in Asia. In many traditional formulations, the aerial parts have been used as anti-inflammatory and antipyretic drugs for the treatment of a variety of chronic and infectious diseases. Neoandrographolide possesses significant anti-inflammatory effects, which implies that it would be one of the major contributing components to participate in the anti-inflammatory effect of A. paniculata. and a potential candidate for further clinical trial.

Acoziborole (previously known as SCYX-7158) is a product of Anacor’s novel boron chemistry, which has produced a number of compounds with efficacy against a range of fungal, inflammatory, and bacterial diseases. Acoziborole was developed as an orally active compound with potent antitrypanosoma activity for the potential treatment of stage 2 human African trypanosomiasis (HAT) or sleeping sickness, a deadly parasitic disease transmitted by the tsetse fly. HAT is an important public health problem in sub-Saharan Africa. Existing therapies suffer from poor safety profiles, difficult treatment regimens, limited effectiveness, and a high cost of goods. Acoziborole is participating in phase II/III clinical trial to study its efficacy and safety in patients infected by HAT due to T.b. Gambiense.

Carnosol is an ortho-diphenolic diterpene with an abietane carbon skeleton with hydroxyl groups at positions C-11 and C-12 and a lactone moiety across the B ring. Carnosol is the product of oxidative degradation of carnosic acid. Carnosol is a naturally occurring phytopolyphenol found in rosemary that functions as an antioxidant, antimicrobial, and anticarcinogen. Carnosol has been shown to inhibit inductions of COX-2 by blocking PKC signaling. Carnosol is an inhibitor of AR and ER α. Several pre-clinical studies have suggested that carnosol selectively targets tumorigenic cell as opposed to non-tumorigenic cells and is safe and tolerable in animals. Carnosol has been shown to elicit chemopreventive effects by (1) blocking the bioactivation of carcinogens, (2) enhancing antioxidant and/or detoxification enzyme activities, (3) suppressing tumor-promoting inflammation, (4) inhibiting cell proliferation and inducing apoptosis selectively in cancer cells, and (5) blocking tumor angiogenesis and invasion.

SAR-405838 is an inhibitor of the interaction between the oncoprotein murine double minute 2 (MDM2) and p53. SAR-405838 was investigated in phase I clinical trials in patients with locally advanced/metastatic solid tumor with wild-type TP53 or with TP53 mutation prevalence below 40%. SAR-405838 had an acceptable safety profile with limited activity in patients with advanced solid tumors.

AZD-8186 is a potent and selective inhibitor of PI3Kβ and PI3Kδ with IC50 of 4 nM and 12 nM, respectively. AZD-8186 is currently in phase 1 clinical trials. Combination therapy using AZD-8186 with androgen deprivation results in long-lasting tumor regression, which persisted after treatment cessation.