Zardaverine (6-(4-difluoromethoxy-3-methoxyphenyl)-3[2H]pyridazinone) is a dual-selective inhibitor of phosphodiesterase III/IV was developed as a potential therapeutic agent for asthma. Zardaverine has been shown to inhibit inflammatory cell function, human peripheral blood mononuclear cells (PBMC) and T-cell proliferation and exert a positive inotropic action on the heart muscle. In animals, zardaverine exhibits both bronchodilatory and anti-inflammatory activities. In order to study the efficacy and safety in man, Zardaverine has been tested in clinical trials for the treatment COPD and asthma. Zardaverine has a modest and short-lasting bronchodilatory effect in patients with asthma. However, due to its fast elimination, the development of zardaverine was terminated in 1991.

Beclabuvir (previously known as BMS-791325), a potent, non-nucleoside inhibitor of the HCV NS5B RNA polymerase. In combination with daclatasvir and asunaprevir drug participates in clinical trials phase III for patients infected with HCV genotype 1, which is the most common genotype worldwide. Recently published data has shown that this combination achieved very high rates of viral eradication.

Propoxur (Baygon) is a carbamate insecticide that has recently attracted considerable attention as a possible treatment option for addressing the bedbug epidemic. Propoxur is a non-systemic insecticide with a fast knockdown and long residual effect used against the turf, forestry, and household pests and fleas. The generally accepted mechanism of toxicity for propoxur involves the inhibition of cholinesterase. Propoxur is also used in pest control for other domestic animals, Anopheles mosquitoes, ants, gypsy moths, and other agricultural pests. It can also be used as a molluscicide. Several U.S. states have petitioned the Environmental Protection Agency (EPA) to use propoxur against bedbug infestations, but the EPA has been reluctant to approve indoor use because of its potential toxicity to children after chronic exposure.

Apatinib is an orally bioavailable, small molecule tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2 and used for the treatment of metastatic gastric cancer or gastroesophageal junction cancer that has progressed or relapsed after chemotherapy. To date, second-line ramucirumab and third-line Apatinib are the only anti-angiogenic approaches that have significantly improved the survival of patients with metastatic gastric cancer. Apatinib exhibited potent, highly-selective inhibition of VEGFR-2, c-kit, c-src, and RET tyrosine kinases. The efficacy of Apatinib monotherapy in patients with metastatic gastric cancer or gastroesophageal junction cancer for whom at least two prior chemotherapy regimens had failed was demonstrated in randomized open-label or double-blind phase II trials and a pivotal placebo-controlled phase III trial, all of which were conducted in China. Further clinical experience and long-term pharmacovigilance are required to definitively establish the efficacy and safety profile of Apatinib, including its use in combination with other chemotherapeutic agents.

Icotinib is an orally available quinazoline-based inhibitor of epidermal growth factor receptor. It selectively inhibits the wild-type and several mutated forms of EGFR tyrosine kinase. The major organ of icotinib metabolism is the liver, with the primarily enzymes being CYP2C19 and CYP3A4 from the cytochrome P450 monooxygenase system. Icotinib Hydrochloride was approved for the treatment of patients with advanced stage Nonsmall cell lung cancer by the State Food and Drug Administration (SFDA) of China. The major drug related adverse reactions of the traditional cytotoxic agents include rash, diarrhea, severe bone marrow suppression, neuropathy, hair loss, and gastrointestinal reactions. Icotinib is under investigation as an active agent against other EGFR mutation-positive cancers, like lung adenocarcinoma, oesophageal cancer, nasopharyngeal cancer and others.

Trelagliptin (SYR-472), a novel dipeptidyl peptidase-4 inhibitor used for the treatment of type 2 diabetes mellitus. Trelagliptin (as the salt Trelagliptin succinate) was approved for use in Japan in March 2015. Takeda, the company that developed Trelagliptin, chose to not get approval for the drug in the USA and EU.

Rociletinib is a novel, potent, small molecule, third generation TKI that irreversibly binds and inhibits EGFR with the common activating (L858R, Del19) and T790M resistance mutations. The proposed indication of rociletinib is for the treatment of patients with mutant EGFR NSCLC who have been previously treated with an EGFR-targeted therapy and have the T790M mutation as detected by an FDA approved test. The results from two Phase 2 studies show that rociletinib 625 mg BID treatment has a favorable benefit:risk profile in patients with recurrent T790M-positive mutant EGFR NSCLC based on clinically meaningful and durable responses and a well-established and acceptable safety profile in this patient population with terminal lung cancer. In May 2016, Clovis Oncology, Inc. announced it has terminated enrollment in all ongoing sponsored studies of rociletinib, including TIGER-3, after the company was notified at meeting with the FDA that it could anticipate receiving a Complete Response Letter (CRL) for the rociletinib NDA on or before the PDUFA date of June 28, 2016. Clovis has also withdrawn its Marketing Authorization Application of rociletinib with European regulatory authorities.

Umirolimus (Biolimus A9), an analogue of sirolimus, is a highly lipophilic macrolide compound developed by Biosensors International as an antiproliferative agent in coronary artery restenosis. Umirolimus has immunosuppressive and anti-inflammatory effects. It is used for the prevention of restenosis.

Asunaprevir is a direct acting antiviral agent (DAA) against the hepatitis C virus Asunaprevir is an inhibitor of the HCV NS3/4A serine protease complex. This NS3/4A enzyme complex is responsible for processing the HCV polyprotein to yield mature viral proteins required for viral replication. The combination of daclatasvir + asunaprevir [Daklinza(®) + Sunvepra(®)], two direct-acting antiviral agents, has been developed by Bristol-Myers Squibb for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 infections, including those with compensated cirrhosis.

Gemigliptin, an orally active, CD26 antigen (dipeptidyl peptidase IV or DPP IV) antagonist, was developed by LG Life Sciences (Seoul, Korea) and was approved by the Ministry of Food and Drug safety in June 2012 for the treatment of Type 2 diabetes mellitus. Zemiglo is the brand name of gemigliptin. The company also signed licensing agreement with multinational pharmaceutical companies including Sanofi (Paris, France), and at present gemigliptin is approved in India, Columbia, Costa Rica, Panama, Ecuador and a few other countries. Registration studies are currently ongoing in several countries including Russia, Mexico and Thailand. Various studies have proven the efficacy and safety of gemigliptin for the treatment of T2DM, both as monotherapy as well as in combination with other anti-diabetic drugs. Gemigliptin binds to the S1, S2, and S2 extensive subsites of the DPP-4 enzyme. The piperidinone group of gemigliptin binds to the S1 subsite, where the upside F atom on the piperidin ring forms a hydrogen bond with the side chain of Tyr631 and the downside F atom makes a hydrophobic interaction with the side chain of Tyr666 and Tyr662. In addition, the key interaction occurs between the CF3 groups on the pyrimidino piperidine and the S2 extensive subsite of the DPP-4 substrate, which enhances the potency of the drug and increases its selectivity as well. Gemigliptin is a reversible and competitive inhibitor of DPP-4 enzyme with a Ki value of 7.25 ± 0.67 nM. It acts as a long-acting DPP-4 inhibitor which inhibits DPP-4 in a dose-dependent manner. In addition, it showed at least >23,000 fold selectivity for proteases such as DPP-8, DPP-9, and fibroblast activating protein – α. By preventing degradation of GLP-1 by DPP-4 inhibition, it increases insulin secretion, reduces glucagon secretion, decreases HbA1c, and prevents β-cell damage. Gemigliptin has also been investigated for the treatment of cancer and cisplatin adverse reaction.