Tanaproget (WAY-166989) is a nonsteroidal progesterone receptor agonist. It has been in Phase-II clinical trials as an oral contraceptive. The compound demonstrated a positive preclinical pharmacological profile in the treatment of endometriosis. The level of progesterone receptors in breast tumours can be used to guide the selection of endocrine therapies for breast cancer patients. Radiolabeled analogues of tanaproget have diagnostic potential as PET imaging agents for breast cancer.

Falnidamol is an epidermal growth factor receptor inhibitor, developed by Boehringer Ingelheim. Falnidamol demonstrated anticancer activity in vitro. The phase I trial was discontinued due to a dose-limiting increase of liver enzymes, low bioavailability of the drug and the detection of a pharmacologically inactive metabolite.

Hydroxytamoxifen (Afimoxifene) is an active metabolite of tamoxifen exerting estrogen receptor modulatory function. In addition, hydroxytamoxifen binds to regulates transcriptional activity of the estrogen-related receptor gamma. ASCEND Therapeutics, Inc. was developing TamoGel (4-hydroxytamoxifen gel) for a variety of estrogen-dependent conditions, including breast cancer, cyclic breast pain and gynecomastia.

Bardoxolone methyl, the C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) known as CDDO-Me or RTA 402, is one of the derivatives of synthetic triterpenoids. Bardoxolone methyl directly blocks IKKbeta activity and thereby the NF-kappaB pathway by interacting with Cys-179 in the IKKbeta activation loop. Binding of bardoxolone methyl to Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) disrupts its critical cysteine residues, leading to the release of the nuclear factor erythroid 2-related factor 2 (Nrf2), which hinders its ubiquitination and finally leads to its stabilization and nuclear translocation. In the nucleus, Nrf2 activates the transcription of phase 2 response genes, leading to a coordinated antioxidant and anti-inflammatory response. In addition, it acts as an antagonist of the peroxisome proliferator-activated receptor gamma. Through Keap1/Nrf2 and nuclear factor-κB pathways, this agent can modulate the activities of a number of important proteins that regulate inflammation, redox balance, cell proliferation and programmed cell death. This agent is generally well tolerated, but it may increase adverse cardiovascular events. Presently, it is being further tested for the treatment of patients with chronic kidney disease, cancer, and pulmonary arterial hypertension.

Apilimod is a small molecule inhibitor of interleukin-12 and interleukin-23 synthesis thereby preventing IL-12/IL-23 mediated immune responses. Apilimod is also observed to inhibit the nuclear accumulation of NF-kappB protein family, and viral infections dependent on phosphatidylinositol-3-phosphate 5-kinase (PIKfyve). Apilimod has been investigated as a potential treatment for a number of autoimmune conditions.

Brivanib is a pyrrolotriazine-based compound and an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antineoplastic activity. It specifically targets and strongly binds to human VEGFR-2, a tyrosine kinase receptor and pro-angiogenic growth factor expressed almost exclusively on vascular endothelial cells. Blockade of VEGFR-2 by this agent may lead to an inhibition of VEGF-stimulated endothelial cell migration and proliferation, thereby inhibiting tumor angiogenesis. Brivanib has a moderate potency compared to VEGFR-2 against VEGFR-1 and FGFR-1 as well. Brivanib is suggested to be efficient in treatment of hepatocellular carcinoma (HCC). As first-line and as second-line therapy brivanib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC in phase II clinical trials. On 3 march 2011, orphan designation was granted by the European Commission to Bristol-Myers Squibb for brivanib alaninate for the treatment of hepatocellular carcinoma.[

Fenmetozole is an alpha-2 adrenergic receptor antagonist which was developed for the treatment of schizophrenic and/or depressed patients, however never reached the market. It was also shown that the drug may reduce symptoms of minimal brain dysfunction in children and antagonize the effect of barbiturates and ethanol.

Cinaciguat acts specifically on oxidized/haem-free soluble guanylyl cyclase by binding to the enzyme's haem pocket and mimicking the nitric-oxide-bound haem group. It is in clinical development for the treatment of acute decompensated heart failure. Cinaciguat had been in phase II clinical trials. However, trials were terminated early because of an excess of hypotension in the cinaciguat arms and subsequent slow enrolment.

Eprodisate (1,3-propanedisulfonate) is a negatively charged, sulfonated molecule of low molecular weight that has structural similarities to heparin sulfate; it is a glycosaminoglycan mimetic that binds to the glycosaminoglycan (GAG) binding site on serum A amyloid (AA) to prevent its interaction with glycosaminoglycan and arrest amyloidosis, or inhibit amyloid deposition. In nonclinical toxicity studies in two animal species (i.e., rat and dog), eprodisate was administered orally at doses of up to 2000 mg/kg/day for 39 weeks: eprodisate showed low toxicity potential at doses several fold higher than the anticipated clinical dose, was well tolerated upon chronic exposure and was found to be nonmutagenic and nonclastogenic. Furthermore, a series of safety pharmacology studies showed that eprodisate does not have any clinically significant effect on major organ function.

Adoprazine (SVL-313) is a full 5-HT1A receptor agonist and full D2/3 receptor antagonist possessing characteristics of an atypical antipsychotic, representing a potential novel treatment for schizophrenia and bipolar disorder. This drug together with some others, e.g. Mazapertine succinate, PF-217830 was discontinued from clinical trials due to either non-optimal pharmacokinetic properties or insufficient therapeutical efficacy.