SRT2104, also known as GSK2245840, is a novel, first in class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. SRT2104 in the phase II of clinical trial to treat type 2 diabetes mellitus and psoriasis also in the phase I for its use in case of colitis. Also was reported, that we report that SRT2104, penetrated the blood-brain barrier, attenuated brain atrophy, improved motor function, and extended survival in a mouse model of Huntington's disease.

Encenicline (EVP-6124; MT-4666) acts as a potent partial and selective agonist at alpha-7 nicotinic acetylcholine receptor. Encenicline significantly improved memory function in animal models. FORUM Pharmaceuticals (formerly EnVivo Pharmaceuticals) is developing encenicline for the treatment of cognition disorders such as schizophrenia and for Alzheimer's disease.

Peficitinib (formerly known as ASP015K) is a pyrrolo[2,3-b]pyridine derivative orally administered once-daily JAK inhibitor in development for the treatment of Rheumatoid Arthritis. In preclinical studied Peficitinib inhibited JAK1 and JAK3 with IC50 of 3.9 and 0.7 nM, respectively. Peficitinib also inhibited IL-2-dependent T cell proliferation in vitro and STAT5 phosphorylation in vitro and ex vivo. Furthermore, Peficitinib dose-dependently suppressed bone destruction and paw swelling in an adjuvant-induced arthritis model in rats via prophylactic or therapeutic oral dosing regimens.In clinical trials, Peficitinib treatment prescribed at 50, 100 and 150 mg amounts each showed statistically significantly higher ACR20 response rates compared to the placebo and response rates increased up to the 150 mg dosage. Adverse events included neutropenia, headache, and abdominal pain. The treatment-emergent adverse events occurring more frequently in the Peficitinib group compared with the placebo group included diarrhea, nasopharyngitis, and increased serum creatine phosphokinase activity. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in the peficitinib 25 and 100 mg cohorts). The authors concluded that treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed an acceptable safety profile.

AZD0328, a spirofuropyridine, is a selective alpha7 nicotinic receptor agonist. This drug participated in clinical trials phase II in patients with schizophrenia. However, studies were terminated because the drug didn’t meet the current target product profile. Besides AZD0328 has been studied in phase I for the treatment of Alzheimer's disease.

Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 pathway, which is over-activated in many types of cancer and has been shown to be an important pathway in cancer stem cell-mediated propagation of cancer. Napabucasin has already shown promising efficacy on different cancer types, both as a monotherapy and in combination with conventional chemotherapeutic agents. Early-phase trials have shown promising anti-tumor efficacy when patients are treated with napabucasin in combination with standard chemotherapy agents, and preclinical results suggest that napabucasin can synergize with chemotherapy agents, such as paclitaxel, to potentially overcome drug resistance. Encouraging phase Ib/II trial results warrant further clinical study with napabucasin and paclitaxel combination therapy, especially in malignancies where there is an urgent and unmet need for effective therapeutics, such as in patients with advanced pancreatic adenocarcinoma.

Aerie Pharmaceuticals, Inc. (Bridgewater, NJ), was developing a novel prostaglandin analog, AR-102, that had 150-fold greater selectivity and 30-fold greater potency at the FP receptor than latanoprost. In preclinical studies, the drug has shown greater IOP-lowering efficacy and alonger duration of action than latanoprost and betterocular tolerability than travoprost. AR-102 was in early-stage clinical development for glaucoma, which was discontinued later..

Ferroheme is formed when iron is inserted into protoporphyrin IX. The active center of hemoglobin and myoglobin consists of iron Ferroheme complex bound through a single, “proximal”, axial histidine (His) to the protein It is an iron containing cofactor that is involved with a wide range of cellular functions including oxygen transport. The antimalarial activity of a number of artemisinin derivatives, both newly synthesized and currently used as drugs, against Plasmodium falciparum in culture shows a correlation with their affinity of binding with Ferroheme.

Nelociguat, a soluble guanylate cyclase (sGC) activator, has been in phase II clinical trials by Bayer for the treatment of erectile dysfunction and heart failure. However, no recent development has been reported. Nelociguat is a direct soluble guanylate cyclase (sGC) stimulator that acts independently of nitric oxide (NO); has an EC50 of 353 nM on P-VASP formation in rat aortic smooth muscle cells. BAY 60-4552 is pharmacologically active major metabolite of Riociguat.