Carmegliptin is a potent, long-acting, selective, orally bioavailable, pyrrolidinone-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. ). DPP-IV is a proline-specific serine protease enzyme that is known to rapidly inactivate two incretin hormones released during food ingestion, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretins are essential for regulating both fasting and postprandial plasma glucose by stimulating insulin secretion, supporting β-cell mass, and inhibiting glucagon production by the α-cells to reduce glucose production by the liver. By selectively inhibiting DPP-IV, carmegliptin prolongs the activity of circulating GLP-1 and GIP and improves their potential to prolong the antidiabetic actions. Carmegliptin is indicated for use as monotherapy or in combination with other oral antihyperglycemic agents for the treatment of Type 2 diabetes.

Dovitinib is an orally active small molecule that exhibits potent inhibitory activity against multiple receptor tyrosine kinases (RTK) involved in tumor growth and angiogenesis. Dovitinib strongly binds to fibroblast growth factor receptor 3 (FGFR3) and inhibits its phosphorylation, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell death. In addition, this agent may inhibit other members of the RTK superfamily, including the vascular endothelial growth factor receptor; fibroblast growth factor receptor 1; platelet-derived growth factor receptor type 3; FMS-like tyrosine kinase 3; stem cell factor receptor (c-KIT); and colony-stimulating factor receptor 1; this may result in an additional reduction in cellular proliferation and angiogenesis, and the induction of tumor cell apoptosis. There are several ongoing Phase I/III clinical trials for dovitinib.

Canertinib or CI-1033 (N-[4-[N-(3-Chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazolin-6-yl]acrylamide) is a pan-erbB tyrosine kinase inhibitor. It selectively inhibits erbB1 (epidermal growth factor receptor), erbB2, erbB3, and erbB4 without inhibiting tyrosine kinase activity of receptors such as platelet-derived growth factor receptor, fibroblast growth factor receptor, and insulin receptor, even at high concentrations. Canertinib was under development by Pfizer Inc as a potential treatment for cancer.

Vatalanib a potent oral tyrosine kinase inhibitor with a selective range of molecular targets, has been extensively investigated and has shown promising results in patients with solid tumors in early trials. Vatalanib selectively inhibits the tyrosine kinase domains of vascular endothelial growth factor (VEGF) receptor tyrosine kinases (important enzymes in the formation of new blood vessels that contribute to tumor growth and metastasis), platelet-derived growth factor (PDGF) receptor, and c-KIT. The adverse effects of vatalanib appear similar to those of other VEGF inhibitors. In the CONFIRM trials, the most common side effects were high blood pressure, gastrointestinal upset (diarrhea, nausea, and vomiting), fatigue, and dizziness.

Dexecadotril is powerful and selective inhibitor of neprilysin. It is anti-hypotensive agent. Dexecadotril was found to possess chemoprotective activity. It might be biologically active against multiple myeloma. It was under clinical evaluation as an intestinal antisecretatory agent.

Gisadenafil is a phosphodiesterase V inhibitor in clinical development at Pfizer. It had been in phase II clinical trials for the treatment of Benign prostatic hyperplasia; Chronic obstructive pulmonary disease; Erectile dysfunction; Overactive bladder. Treatment-emergent adverse events were: headache, myalgia, dyspepsia, back pain.

Motexafin gadolinium is a novel, MRI-detectable, an anticancer agent that enhances the cytotoxic potential of radiation therapy through several mechanisms, including depleting intracellular reducing metabolites that are necessary for repairing the oxidative damage induced by irradiation. Motexafin gadolinium catalyzes the oxidation of intracellular reducing metabolites such as ascorbate, glutathione, nicotinamide adenine dinucleotide phosphate, and protein thiols, generating reactive oxygen species in a process known as futile redox cycling. The depletion (through oxidation) of these reducing metabolites removes the substrate necessary in a cell to repair oxidative damage induced by radiation and, left unrepaired, such radiation-induced oxidative DNA damage is converted into lethal double-stranded breaks. Motexafin gadolinium has tumor-specific uptake, normal tissue sparing, and tolerable and reversible toxicities in clinical trials. Motexafin gadolinium use in conjunction with whole-brain radiation therapy (WBRT) has demonstrated an improvement in neurocognitive decline, neurologic progression, and quality of life in patients with brain metastases from Non-small-cell lung carcinoma. Motexafin gadolinium use in conjunction with radiosurgery and whole brain radiation therapy in the setting of brain metastases is currently being studied, as is Motexafin gadolinium with radiation and temozolomide in patients with glioblastoma multiforme.

Amuvatinib (formerly known as MP470) is an oral multi-targeted tyrosine kinase inhibitor, which play critical roles in transducing growth signals to cancer cells. It suppresses c-MET, c-RET and the mutant forms of cKIT, PDGFR and FLT3. It also disrupts DNA repair likely through suppression of homologous recombination protein Rad51, an important survival pathway in many human cancers. In vitro and in vivo data have demonstrated amuvatinib synergy with DNA damaging agents including etoposide and doxorubicin. Overall, in the amuvatinib clinical development program, over 200 subjects were exposed to at least one dose of amuvatinib. In the Phase 1b clinical study in combination with carboplatin and etoposide, responses in small cell lung cancer (SCLC), neuroendocrine as well as other tumor types were observed. Human pharmacokinetic data suggest that co-administration of amuvatinib did not alter exposures of standard of care agents including carboplatin, etoposide, doxorubicin, paclitaxel, topotecan or erlotinib as measured by overall exposure. In the first-in-human study, durable clinical benefit was observed in the gastrointestinal stromal tumors (GIST) with modulation of Rad51 observed in skin punch biopsies. In clinical trials, amuvatinib has demonstrated a wide therapeutic window and shows minimal toxicity in the expected therapeutic dose range, despite suppressing several signaling pathways within cells. However, in spite of this, this drug was discontinued, because it was not pre-specified primary endpoints in the clinical proof of concept (cPOC) stage. But the combination of MP470 and Erlotinib, which target the HER family/PI3K/Akt pathway may represent a novel therapeutic strategy for prostate cancer.

Talabostat is a prolineboronate ester derivative patented by Boehringer Ingelheim Pharmaceuticals, Inc. as an antineoplastic agent. Talabostat inhibits dipeptidyl peptidases, such as fibroblast activation protein (FAP), resulting in the stimulation of cytokine and chemokine production and specific T-cell immunity and T-cell dependent activity. Talabostat has been shown to cause caspase-1 activation and IL-1β induction in macrophages, which in turn causes upregulation of the cytokines and chemokines that characterize the responses to talabostat, both in vitro and in tumor-bearing mice. Talabostat may also stimulate the production of colony stimulating factors, such as granulocyte colony stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis. In clinical trials, the combination of talabostat and cisplatin was well tolerated compared to historical data using cisplatin alone. The most frequent adverse events were nausea, vomiting, fatigue, anemia, edema, and constipation. Unfortunately was no evidence that Talabostat enhanced the clinical activity of other anticancer drugs and further development was discontinued.

Sergliflozin, a novel oral selective low-affinity sodium glucose cotransporter (SGLT2) inhibitor, improves hyperglycemia by suppressing renal glucose reabsorption, in which SGLT2 participates as a dominant transporter. Its prodrug form, sergliflozin etabonate, is orally available and is converted to sergiflozin upon absorption. Development of sergliflozin has been discontinued in favor of remogliflozin.