Alvocidib (also known as Flavopiridol or HMR-1275) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development for the treatment of acute myeloid leukemia, by Tolero Pharmaceuticals, Inc. As a broad spectrum CDK inhibitor, Alvocidib can inhibit cell cycle progression in either G1 or G2 and induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. Alvocidib exhibits potent cytotoxicity against a wide variety of tumor cell lines (LNCAP, HCT116, A2780, K562, PC3, and Mia PaCa-2) with IC50 values ranging from 16 nM for LNCAP to 130 nM for K562. Administration of Alvocidib at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, and active against the human A2780 ovarian carcinoma implanted sc in nude mice). Alvocidib treatment at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. Tolero Pharmaceuticals Inc. announced that the FDA has granted orphan drug designation for Alvocidib, its cyclin-dependent kinase small molecule inhibitor, for the treatment of patients with acute myeloid leukemia.

Ibutamoren (L-163,191 MK-0677) is a spiropiperidine agonist of the ghrelin receptor and a growth hormone secretagogue. Ibutamoren mimics the actions of growth hormone releasing peptide-6 to increase serum levels of serum insulin-like growth factor-I (IGF-I). Orally active Ibutamoren was being developed by Merck & Co. for a variety of indications, including fibromyalgia, muscle wasting/weakness in patients with chronic kidney disease, Alzheimer's disease and fractures.However, there has been no recent development reported or development has been discontinued for these indications.

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.[

Berubicin, an anthracycline derivative, is a DNA binding agent and potent topoisomerase II poison. Reata Pharmaceuticals were developing it as a treatment for brain cancer as it can breach the blood-brain barrier. It had also been in early clinical trials for the treatment of lung cancer and malignant gliomas. However, studies have been terminated. In October 2006, it was granted orphan drug designation from the FDA for the treatment of malignant gliomas. According to a CNS Pharmaceuticals media release in April 2018, berubicin will be studied for glioblastoma patients, these investigations will be funded in part by an equity crowdfunding campaign.

Ibiglustat (GZ/SAR402671 or Genz-682452) is a small molecule inhibitor of glucosylceramide synthase. Ibiglustat has been demonstrated to effectively lower glycosphingolipid synthesis. Genzyme, a Sanofi Company is developing Ibiglustat for the treatment of Parkinson's Disease, Gaucher Disease, and Fabry Disease.

LY404039 [(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid] is an agonist of orthosteric metabotropic glutamate receptor (mGluR)2/3. In addition, it acts as an agonist at dopamine D2 receptors. LY404039 demonstrated broad antipsychotic and anxiolytic efficacy across multiple animal models. LY-2140023 is a methionine amide prodrug of LY-404039 being developed by Eli Lilly & Co for the potential oral treatment of schizophrenia.

Adrogolide is a chemically stable prodrug of the dopamine D1 receptor agonist A-86929. Adrogolide is rapidly converted in plasma to A-86929. A-86929 has high affinity and functional selectivity for the dopamine D1 receptor. Adrogolide has been in phase II clinical trials for the treatment of Parkinson's disease and cocaine abuse. However, this research has been discontinued. The adverse events associated with its use of adrogolide were of mild-to-moderate severity and included injection site reaction, asthenia, headache, nausea, vomiting, postural hypotension, vasodilitation, and dizziness.

MK-0359 (L-454560) is a selective and potent type 4 phosphodiesterases (PDE4) inhibitor, which binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. This compound successfully has passed the phase II clinical trial for the treatment of asthma, Pulmonary Disease, Chronic Obstructive (COPD) and Rheumatoid Arthritis. However, there is no information about the further research of this drug.

Ravuconazole is a triazole with antifungal properties that inhibits cytochrome P450 sterol 14a-demethylase, an enzyme involved in sterol synthesis, resulting in lysis of the fungal cell wall and fungal cell death. It was investigated for the treatment of aspergillosis, candidiasis, and onychomycosis, but these studies were discontinued. Ravuconazole is now in phase II clinical trials to investigate efficacy in preventing fungal infections in patients undergoing chemotherapy and stem cell transplantation.

Lometrexol, formerly known as DDATHF; LY 264618; T-64 was the first glycinamide ribonucleotide formyl transferase (GARFT) inhibitor to be investigated clinically. Lometrexol had been in phase II clinical trial for the treatment non-small cell lung cancer (NSCLC). However, the studies have been discontinued by Tularik Inc, because Company had suggested, that drug would face competition from other companies in the indication