Saroglitazar, a dual peroxisome proliferator-activated receptor PPAR-α/γ agonist, was an emerging therapeutic option on glycemic and lipid parameters. The Zydus Group has launched LipaglynTM ((Saroglitazar) in India for diabetic dyslipidemia and hypertriglyceridemia with type 2 diabetes mellitus not controlled by statin therapy. In addition, saroglitazar participated in phase II clinical trials that completed enrolment in patients with primary biliary cholangitis and in patients with non-alcoholic steatohepatitis.

RO-638695 (also known as Miridesap, CPHPC and GSK-2315698) is an antineoplastic and a serum amyloid P component inhibitor. RO-638695 almost completely depletes circulating serum amyloid P component (SAP), but a small amount of SAP is left for recognition by subsequently administered therapeutic IgG anti-SAP antibodies. SAP is a blood protein that is the target of a novel immunotherapy approach. RO-638695 has therefore been evaluated in phase I and II clinical trials for its safety and potential in treatment of diseases like Alzheimer’s disease, HIV infection and other diseases with systemic amyloid deposition.

Arena Pharmaceuticals was developing APD-597 (JNJ-38431055), a small molecule, an orally active agonist of the G-protein coupled receptor 119 (GPR119), for the treatment of Type 2 diabetes mellitus. JNJ-38431055 was selected for preclinical development based on a good balance between agonist potency, intrinsic activity and in particular on its good solubility and reduced drug-drug interaction potential. In addition, extensive in vivo studies showed a more favorable metabolic profile that may avoid the generation of long-lasting metabolites with the potential to accumulate in clinical studies. In humans, single-dose oral JNJ-38431055 increased postmeal plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) concentrations but did not significantly decrease glucose excursion or increase insulin secretion. However, in a graded glucose infusion study, JNJ-38431055 was shown to induce a higher insulin secretion rate (ISR) relative to placebo at elevated plasma glucose levels. These studies provide evidence for the potential efficacy of JNJ-38431055 as an antidiabetes agent in humans.

24-Hydroxycalcidiol (24,25-dihydroxy vitamin D3) is a circulating metabolite of vitamin D3. 24,25(OH)2D3 functions by activation of Vitamin D receprtor and promotion of ostecalcin expression, but is less effective than other D3 metabolite, 1alpha,25(OH)2D3. There is conflicting evidence on efffect of 24-hydroxycalcidiol on bone metabolism. In several animal studies it was demonstrated that 24-hydroxycalcidiol was able to stimulate calcification of bone and restore the reduction in bone mineral apposition rate. However, no beneficial effect of 24R,25(OH)2D3 treatment of postmenapausal women on bone mineral density or bone loss and calcium metabolism were observed.

Tipredane is one of the compounds of a new series of sulfur-containing steroids synthesized at The Squibb Institute for Medical Research and is being developed for topical treatment of human dermatoses. Tipredane is structurally unique in that the classical l7-beta two-carbon side chain and the 17-alpha hydrogen of the steroid have been replaced by two alkylthio substituents. Tipredane has been shown to possess moderate to potent anti-inflammatory activity in various animal models, and to exhibit favorable separation of local anti-inflammatory activity from adverse systemic effects in both animals and humans. After oral administration, [3H]tipredane was rapidly absorbed, metabolized, and excreted into urine and feces. Metabolism of tipredane was rapid and complex, with significant species differences, although the disposition in rhesus and cynomolgus monkeys seemed to be similar to humans. Tipredane had been investigated as the therapeutic agent for the treatment of allergic rhinitis, asthma and skin disorders. However, this development was discontinued.

Belnacasan (VX-765), and its active metabolite VRT- 043198, is a novel and irreversible IL-converting enzyme/ caspase-1 inhibitor. VRT-043198 exhibits 100- to 10,000-fold selectivity against other caspase-3, -6 and -9. It exhibited potent inhibition against ICE/caspase-1 and caspase-4 with Ki of 0.8 nM and less than 0.6 nM, respectively. And VRT-043198 also inhibits IL-1β release from both PBMCs and whole blood with IC50 of 0.67 uM and 1.9 uM, respectively. Belnacasan inhibits the release of IL-1, IL-18 and IL-33. Belnacasan has shown to inhibit acute partial seizures in preclinical models and has shown activity in preclinical models of chronic partial epilepsy that do not respond to currently available compounds for epilepsy. In addition, it seems to reduce disease severity and the expression of inflammatory mediators in models of rheumatoid arthritis and skin inflammation. Belnacasan had been in phase II clinical trials by Vertex for the treatment of epilepsy. However, this study has been terminated later.

PF-04418948 is an orally active, potent, and selective EP2 receptor antagonist. It is used as a tool compound to study involvement of EP2 receptor in various pathologies. In combination with EP4 antagonist, PF-04418948 attenuates PGE2-induced airway microvascular leak in model of asthma, and PGE2-induced gut dismotility.

Flumatinib (HHGV678) is an orally bioavailable antineoplastic tyrosine kinase inhibitor. Flumatinib inhibits the wild-type forms of Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and mast/stem cell growth factor receptor (SCFR; c-Kit) and forms of these proteins with certain point mutations. Flumatinib was extensively metabolized after oral administration, and the major metabolic pathways observed were amide hydrolysis, demethylation, oxidation, and glucuronide conjugation. It is in phase III clinical trials for the treatment of Chronic myeloid leukemia (in China).