ST-101 (also known as ZSET1446) is an azaindolizinone derivative patented by Zenyaku Kogyo Kabushiki Kaisha for the treatment of Alzheimer's disease and improvement of cerebral function. In preclinical models, ST-101 stimulates acetylcholine release and improves methamphetamine-induced impairment of recognition memory in mice by activating extracellular signal-regulated kinase 1/2. Impaired neurogenesis observed in olfactory bulbectomized mice was significantly improved by chronic administration with ST-101. We confirmed that administration with mecamylamine, a nicotinic acetylcholine receptor antagonist, inhibits ST-101-enhanced neurogenesis in the dentate gyrus. ST-101 administration also restored decreased phosphorylation of Akt and extracellular signal-regulated kinase in the dentate gyrus of olfactory bulbectomized mice.

Mirogabalin, a selective alpha 2 delta ligand binds to the α2δ subunits of voltage-dependent calcium channels and thus blocks the channel. This drug was developed by Daiichi Sankyo and in January 2019 was approved in Japan for the treatment of neuropathic pain and for the postherpetic neuralgia.

AMG-925, a dual FLT3/CDK4 inhibitor, has been developed to overcome resistance to FLT3 inhibitors, which is a serious clinical issue in treating acute myelogenous leukemia (AML). AMG-925 inhibits FLT3, including many FLT3 mutants reported to date. AMG-925 inhibits the proliferation of a panel of human tumor cell lines including Colo205 (Rb(+)) and U937 (FLT3(WT)) and induced cell death in MOLM13 (FLT3(ITD)) and even in MOLM13 (FLT3(ITD, D835Y)), which exhibits resistance to a number of FLT3 inhibitors currently under clinical development. At well-tolerated doses, AMG-925 leads to significant growth inhibition of MOLM13 xenografts in nude mice, and the activity correlates with inhibition of STAT5 and Rb phosphorylation. AMG-925 is in Phase I clinical trials for the treatment of Acute myeloid leukaemia.

LY-2456302 or CERC-501 (now JNJ-67953964) is a non-peptide, centrally-penetrant, potent, short-acting kappa opioid receptor (KOR)-selective antagonist with pharmacokinetic properties favorable for clinical development and activity in animal models predictive of efficacy in mood and addictive disorders. It is under development for depression and substance abuse disorders.

Dapansutrile is an inhibitor of the NLRP3 inflammasome, developed by Olatec Therapeutics LLC. NLRP3 inflammasome is a driver of sterile inflammation in response to myocardial ischemia-reperfusion and other inflammatory conditions. Dapansutrile limits infarct size and prevents left ventricular systolic dysfunction in the mouse model of ischemia-reperfusion injury and suppresses joint inflammation in the mouse model of acute arthritis. Dapansutrile demonstrated a clinical and inflammatory cytokine response in a clinical trial for the treatment of acute gout and is being investigated for the treatment of Systolic Heart Failure and Schnitzler Syndrome.

INT-131, a novel, non-thiazolidinedione (TZD), selective peroxisome proliferator-activated receptor (PPAR) gamma modulator and partial agonist, which was investigated in phase II of clinical trial for the treatment of type 2 diabetes mellitus (non-insulin dependent diabetes) and Multiple Sclerosis, Relapsing Remitting. The concept of selective modulation involves targeting and activating specific genes to minimize side effects while maintaining therapeutic benefits. In vitro, INT-131 attenuated adipogenic properties, indicating moderate PPAR gamma activation/cofactor recruitment compared with the full agonistic properties of TZD compounds.