Evacetrapib (LY2484595) is a novel benzazepine-based CETP inhibitor that has been developed at Lilly Research Laboratories. Evacetrapib inhibits CETP with IC50 of 5.5 nM, elevates HDL cholesterol without increases in aldosterone or blood pressure. Phase 3. On 01 Sep 2016 Eli Lilly terminates the phase III ACCENTUATE trial in Hyperlipidaemia (Adjunctive treatment) in USA and Puerto Rico (PO) due to insufficient efficacy (NCT02227784).

Pevonedistat (MLN4924), discovered by Millennium, is a small molecule inhibitor of the NEDD8-Activating Enzyme (NAE), a key component of the protein homeostasis pathway. MLN4924 is a mechanism-based inhibitor of NAE and creates a covalent NEDD8-MLN4924 adduct catalyzed by the enzyme. The NEDD8-MLN4924 adduct resembles NEDD8 adenylate, the first intermediate in the NAE reaction cycle, but cannot be further utilized in subsequent intraenzyme reactions. The stability of the NEDD8-MLN4924 adduct within the NAE active site blocks enzyme activity, thereby accounting for the potent inhibition of the NEDD8 pathway by MLN4924. This drug is in phase II clinical trial for the treatment acute myeloid leukemia, chronic myelomonocytic leukemia and myelodysplastic syndromes. In addition in phase I for treatment acute lymphoblastic leukemia. The ability of MLN4924 to cross the blood-brain barrier, its low toxicity, and clinical efficacy in other cancers suggests that this drug is an attractive treatment against glioblastomas.

Aganepag isopropyl, an IOP-lowering agent, is an antiglaucoma agent. It is a selective EP2 receptor agonist.

Aganepag isopropyl, an IOP-lowering agent, is an antiglaucoma agent. It is a selective EP2 receptor agonist.

Profadol is a pyrrolidine derivative patented in the 1960s by pharmaceutical company Parke-Davis as opioid analgesic. Profadol acts as a mixed agonist-antagonist of the μ-opioid receptor and in preclinical studies, Profadol precipitates abstinence in morphine-dependent monkeys and can reverse pethidine- induced narcosis in nondependent monkeys. In morphine-dependent human subjects, Profadol was also found to pre¬cipitate acute abstinence syndromes, with a potency 40 to 50 times less than that of nalorphine. Profadol, unlike other morphine-antagonists, does not produce nalorphine-like subjective effects. Over a fourfold range of doses, this drug was found to produce subjective effects indistinguishable from those of morphine. Also unlike other morphine-antagonists, profadol is quite active on the "classical" rodent tests for analgesia. It is about 1.3 times as potent as pethidine on the mouse hot-plate test, and about four times as potent on the rat tail-pressure test.

Piritrexim is a synthetic antifolate agent with antiparasitic, antipsoriatic and antitumor properties. Piritrexim inhibits the enzyme dihydrofolate reductase, thereby disrupting folate metabolism and DNA synthesis and cell division. A theoretical advantage of piritrexim over trimetrexate is a lack of any known effects on histamine metabolism, which may lower the risk of hypersensitivity reactions. Piritrexim is a nonclassical antifolate for antitumor and parasitic chemotherapy that passively diffuses into cells and hence do not have to depend on folylpoly-gamma-glutamate synthetase or the reduced folate carrier. Because piritrexim is not a substrate for polyglutamation, the drug is not selectively retained within cells for prolonged periods. Piritrexim has a reliably high oral bioavailability of about 75%, which has led to its development as an oral lipophilic antifolate. Most commonly, it has been administered in oral daily doses of 75 to 150 mg bid or tid every 5 days, with cycles repeated every 3 weeks. Oral absorption is rapid, with peak plasma levels appearing at 1.5 hours after ingestion. Elimination occurs primarily via hepatic metabolism of the drug to active metabolites, and the terminal half-life of the parent compound is about 1.5 to 4.5 hours. Single-agent oral piritrexim has clinical activity in melanoma, urothelial cancers, and head and neck cancers. Tolerable combinations of piritrexim with cisplatin, fluorouracil, and leucovorin have been tested, with promising results achieved in head and neck cancer. An interesting attempt to alternate piritrexim with methotrexate did not have any greater activity than methotrexate alone.

Moxastine is a diarylmethane derivative with an antihistamine and anticholinergic activities.

FERTIRELIN is an analog of luteinizing hormone releasing factor. The drug has been used since 1981 in Japan to treat various types of reproductive failure in cattle.

Onalespib (AT13387; (2,4-dihydroxy-5-isopropyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl] methanone, l-lactic acid salt), is wholly owned by Astex, a novel, high-affinity HSP90 inhibitor, which is currently being clinically tested, has shown activity against a wide array of tumor cell lines, including lung cancer cell lines. As a targeted inhibitor of Hsp90, onalespib has the potential to control the proliferation of multiple solid tumors and hematological malignancies where uncontrolled cell growth is dependent on the interaction between Hsp90 and its client proteins. Astex is pursuing an approach based on the observation that addition of onalespib to a molecularly targeted agent may delay the emergence of resistance to the agent, and hence prolong the window of therapeutic benefit. Onalespib is currently being evaluated via a CRADA with the National Cancer Institute (NCI) in various tumor types, and in a Phase 1/2 clinical study in combination with AT7519, Astex CDK inhibitor.