Valopicitabine is a nucleoside analog and the orally bioavailable prodrug of NM107 that competitively inhibits HCV NS5B polymerase, causing chain termination. Valopicitabine had been in phase II clinical trial for once-daily oral treatment of Hepatitis C virus infection. However, because of the overall risk/benefit profile of subjects undergoing clinical trials, further development of the drug has been temporarily placed on hold by the Swiss drug major Novartis and USA-based Idenix Pharmaceuticals company and the FDA.

Navarixin (SCH 527123) is an oral antagonist of CXC receptors 1 and 2. The drug is currently under Phase II trial for the treatment of psoriasis, COPD and asthma.

Cerdulatinib is an oral, dual spleen tyrosine kinase (Syk) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways that promote cancer cell growth in certain hematologic malignancies – the B-cell receptor pathway via Syk and key cytokine receptors via JAK Being developed to treat patients with hematologic cancers, specifically those who have relapsed or who have not responded to prior therapies. Cerdulatinib is in Phase 2 study evaluating the safety and efficacy of cerdulatinib in patients with relapsed/refractory B-cell malignancies who have failed multiple therapies.

PF-04691502 is a PI3K/mTOR dual inhibitor. It was tested in phase 2 clinical trials against endometrial cancer and breast cancer, but its development was discontinued due to unacceptable toxicity.

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.

Sapanisertib is an oral dual inhibitor of mTORC1/mTORC2, discovered by Intellikine for the treatment of cancer. The drug is being tested in phase II of clinical trials for different cancers among which are sarcoma, hepatocellular carcinoma, etc. The drug is currently developed by Takeda with breast cancer, renal cancer and endometrial cancer being the main target indications.

Oprozomib (PR-047) is an orally bioavailable derivative of carfilzomib, with similar biological activity, i.e. inhibition of the chymotrypsin-like activity of the proteasome. It inhibits the activity of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome; this may result in an accumulation of unwanted or misfolded proteins. Disruption of various cell signaling pathways may follow, eventually leading to the induction of apoptosis and inhibition of tumor growth. Oprozomib (PR-047) is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase I/II trial ongoing.

I-BET-762 (GSK 525762) is a small molecule benzodiazepine, by 'mimicking' acetylated histones interferes with the recognition of acetylated histones by BET family of bromodomains (BRD2, BRD3, and BRD4), which disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumour cell growth. GlaxoSmithKline is developing GSK 525762 for the oral treatment of solid tumours and haematological malignancies.

Defactinib is an oral, investigational drug candidate for the treatment of various solid tumors. Through dual inhibition of FAK and PYK2, defactinib targets key resistance mechanisms in the tumor microenvironment (TME), including limited local immune response, dense stroma, and resident cancer stem cells, that may limit the effectiveness of current and investigational treatments. Treatment-related adverse events are: unconjugated hyperbilirubinemia, fatigue and headache.

N6022 is a novel, first-in-class drug with potent reversible inhibitory activity against S-nitrosoglutathione reductase (GSNOR) and a potential agent for the treatment of acute asthma and cystic fibrosis (CF). Decreased levels of GSNO in the lungs of asthmatics and cystic fibrosis patients have been attributed to increased GSNO catabolism via GSNO reductase (GSNOR) leading to loss of GSNO- and NO- mediated bronchodilatory and anti-inflammatory actions. N6022 restore GSNO levels by inhibiting GSNOR. Inhibition of GSNOR by N6022 has shown safety and efficacy in animal models of asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease. N6022 reduced bronchoconstriction and pulmonary inflammation in a mouse model of asthma. The significant bronchodilatory and anti-inflammatory actions of N6022 in the airways are consistent with restoration of GSNO levels through GSNOR inhibition.