AMG-925, a dual FLT3/CDK4 inhibitor, has been developed to overcome resistance to FLT3 inhibitors, which is a serious clinical issue in treating acute myelogenous leukemia (AML). AMG-925 inhibits FLT3, including many FLT3 mutants reported to date. AMG-925 inhibits the proliferation of a panel of human tumor cell lines including Colo205 (Rb(+)) and U937 (FLT3(WT)) and induced cell death in MOLM13 (FLT3(ITD)) and even in MOLM13 (FLT3(ITD, D835Y)), which exhibits resistance to a number of FLT3 inhibitors currently under clinical development. At well-tolerated doses, AMG-925 leads to significant growth inhibition of MOLM13 xenografts in nude mice, and the activity correlates with inhibition of STAT5 and Rb phosphorylation. AMG-925 is in Phase I clinical trials for the treatment of Acute myeloid leukaemia.

Sevitropium is a bronchospasmolytic agent.

Lunasine is an alkaloid present in bark and leaves of Lunasia quercifolia (Rutaceae). It does not relate to bioactive peptide lunasin isolated from soybean.

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.

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.

The immunosugar N-9-methoxynonyldeoxynojirimycin (SP-187, UV-4B) is an inhibitor of both glucosidases I and II. In preclinical studies, it displayed inhibition of dengue and influenza virus infection. The compound developed by Emergent BioSolutions and evaluated in phase 1 clinical trials on healthy subjects.

Trantelinium bromide is an anticholinergic and spasmolytic drug, used for the treatment of gastric ulcers.

PM-00104 (Zalypsis®) is a synthethic tetrahydroisoquinolone alkaloid, which is structurally similar to many marine organisms. PM-00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA breaks. Immunohistochemical studies in tumors also demonstrated histone-H2AX phosphorylation and p53 overexpression. PM-00104 has progressed into phase II clinical trials to treat Ewing sarcoma, urothelial carcinoma, multiple myeloma, endometrial and cervical cancer. The phase II study concluded that there were no objective responses in the cohort of 16 evaluable patients with Ewing sarcoma. The study of Urothelial carcinoma treatment was terminated early because there seemed to be no benefit from the current therapy. Moreover, PM-00104 as a single-agent did not prove to be an effective therapy for patients with advanced/metastatic endometrial or cervical cancer. None achieved objective tumor response was in phase II study for the treatment of advanced/metastatic endometrial or cervical cancer. Preliminary data showed PM-00104 to be safe to use in the treatment of multiple myeloma but the complete results from this trial have not been published.