Clometherone is an investigational derivative of progesterone, possessing antiestrogen and antiandrogen activities. It was developed by Eli Lilly in the 1960s and was found to significantly suppress the estrone induced uterine hypertrophy in mice at an oral or subcutaneous dose of 10ug. In a clinical trial, administration of clometherone to adult males lead to a slight increase in sebum production.

Gedatolisib (PF-05212384, PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ and mTOR, originally being developed by Wyeth. Upon intravenous administration, gedatolisib inhibits both PI3K and mTOR kinases, which may result in apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K. Significant antitumor efficacy and a favorable pharmacokinetic/safety profile justified clinical evaluation of Gedatolisib. Gedatolisb is in phase II clinical trials by Pfizer for the treatment of acute myeloid leukaemia. Gedatolisb is in phase I clinical trials for the treatment of solid tumours.

Mannomustine is a substance synthesized as one of a series of compounds linking the actively cytotoxic chemical group beta-chlorethylamine with a naturally occurring substance, mannitol. Mannomustine is an alkylating agent with antineoplastic properties. It was being studied in the treatment of hematologic malignancies.

METHYLPARABEN SUBEROHYDROXAMIC ACID PHENYL ESTER (more known as Remetinostat), a histone deacetylase (HDAC) inhibitor, was developed for the treatment of cutaneous T cell lymphoma (CTCL). This drug is participating in phase II clinical trial to evaluate the efficacy, safety, and tolerability to skin lesions in patients with early-stage cutaneous T-cell lymphoma. In May 2019 was announced the positive results from phase II trial of remetinostat in basal cell carcinoma (BCC) patients. Initial results suggest that remetinostat gel offers a potentially effective and well-tolerated, non-surgical intervention for the treatment of localized BCCs. The unique design of remetinostat enables topical application, making it active only in the skin. As soon as it reaches the blood stream, it is degraded, avoiding the side effects associated with other HDAC inhibitors. Besides, remetinostat was studied as the treatment of plaque psoriasis; however, this study was discontinued.

AT-406 (DEBIO-1143, SM-406), is a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). AT-406 inhibits cancer cell growth in various human cancer cell lines. It has good oral bioavailability in mice, rats, non-human primates, and dogs, is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Debiopharm under a licence from Ascenta Therapeutics is developing AT-406 for the treatment of cancers.

The BET-bromodomain inhibitor OTX015 (MK-8628) was initially developed by Mitsubishi Tanabe Pharma Corporation, but then was licensed by OncoEthix, privately held biotechnology company. OTX015 is a selective bromodomains: BRD2, BRD3, and BRD4 inhibitor and inhibits their binding to AcH4. Bromodomains have an important role in the targeting of chromatin-modifying enzymes to specific sites, including methyltransferases, HATs and transcription factors and regulate diverse biological processes from cell proliferation and differentiation to energy homeostasis and neurological processes. OTX015 has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models. Oral administration of OTX-015 markedly inhibited tumor growth and reduced tumor volume. OTX015 is currently in Phase 1b studies for the treatment of hematological malignancies and advanced solid tumors such as Triple Negative Breast Cancer, Non-small Cell Lung Cancer, Castrate-resistant Prostate Cancer (CRPC) and Pancreatic Ductal Adenocarcinoma. In addition, OTX015 was in phase II for the treatment of Glioblastoma Multiforme, but there were not detected clinical activity of the drug in the treatment populations and trial was closed.

Tarenflurbil (Flurizan or R-flurbiprofen) is the single enantiomer of the racemate NSAID flurbiprofen. Tarenflurbil is a first in class, selective amyloid-beta42 (A42) lowering agent (SALA), which acts by modulating the activity of gamma-secretase, an enzyme that converts amyloid precursor protein to amyloid-beta. The reduction of A42 may prevent the development of the amyloid plaques thought to be a key pathological process associated with Alzheimer’s disease. For several years, research and trials for the drug were conducted by Myriad Genetics, to investigate its potential as a treatment for Alzheimer's disease. In a brief statement issued June 30, Myriad Genetics reports that tarenflurbil (Flurizan) failed to have a significant effect in a phase 3 trial of patients with mild Alzheimer's disease (AD). The failure of Flurizan™ is generally attributed to its insufficient pharmacodynamics, i.e., inadequate ability to penetrate the brain and engage its target protein at doses sufficient to yield an effect. Two additional Phase 3 trials were terminated and further development of Flurizan™ was discontinued. Separate clinical development of Flurizan™ for prostate cancer has also been discontinued following negative Phase 2 results. Tarenflurbil activates c-Jun N terminal kinase, increases AP-1 binding to DNA, and downregulates cyclin D1 expression, resulting in the arrest of tumour cells in the G1 phase of the cell cycle and apoptosis. This agent also affects the expression of nuclear factor kappa B, a rapid response transcription factor that stimulates the immune response to tumour cells. Tarenflurbil does not inhibit the enzyme cyclooxygenase. The Fraunhofer Institute for Molecular Biology and Applied Ecology is currently developing tarenflurbil for the treatment of relapsing, remitting multiple sclerosis.

Danusertib is a serine/threonine kinase inhibitor of multiple kinases, including aurora-A, B, and C. It also inhibits several cancer related tyrosine kinases as well as Abl, Trk-a, fibroblast growth receptor-1 and Ret. Danusertib is in phase II trials for the treatment of solid tumours, prostate cancer and chronic myeloid leukemia (CML). The most frequently reported side effects were neutropenia, nausea, anorexia, fatigue, and diarrhea.

Ipatasertib, an investigational Akt inhibitor, is currently in clinical development based on its potential to specifically target Akt in tumors with activated Akt signaling. Preclinical data have shown that ipatasertib selectively decreased cell viability and increased apoptosis in tumor cell lines characterized by activated Akt. Ipatasertib is advancing in clinical development including three Phase 2 trials in patients with breast cancer, gastric cancer and prostate cancer. The most commonly reported adverse events associated with Ipatasertib were Grade 1-2 diarrhea, nausea, fatigue, vomiting, decreased appetite and rash.