Tofimilast is a potent phosphodiesterase-4 (PDE4) inhibitor with low oral bioavailability and no emesis-associated behaviors in ferrets at plasma concentrations up to 152 ng/ml. Tofimilast exhibited an apparent slower absorption through the rat lung after administration as a dry powder, although absorption half-life values were <1 h and therefore the significance of a formulation effect for this compound is questionable. Tofimilast was tested as a therapeutic agent against asthma and chronic obstructive pulmonary disease but development has been discontinued due to lack of efficacy.

VS-5584 is a potent and selective oral small molecule inhibitor of all 4 PI3K isoforms and mTORC1 and mTORC2. VS-5584 inhibits mTOR, PI3Kα/β/δ/γ with IC50 of 3.4 nM and 2.6-21 nM, respectively. Verastem has patent protection of VS-5584 through 2029, and has received orphan drug designation for VS-5584 in mesothelioma in the US and EU. Verastem is currently conducting a Phase 1 trial of VS-5584 in patients with advanced solid tumors and lymphomas.

Ajulemic acid, designated as Resunab™, is being developed by Corbus Pharmaceuticals, for the treatment of cystic fibrosis, systemic sclerosis, systemic lupus erythematosus.Ajulemic acid (AJA) is a first-in-class, synthetic, orally active, cannabinoid-derived drug that preferentially binds to the CB2 receptor and is nonpsychoactive. In preclinical studies, and in Phase 1 and 2 clinical trials, AJA showed a favorable safety, tolerability, and pharmacokinetic profile. It also demonstrated significant efficacy in preclinical models of inflammation and fibrosis. It suppresses tissue scarring and stimulates endogenous eicosanoids that resolve chronic inflammation and fibrosis without causing immunosuppression. AJA is currently being developed for use in 4 separate but related indications including systemic sclerosis (SSc), cystic fibrosis, dermatomyositis (DM), and systemic lupus erythematosus. Phase 2 clinical trials in the first 3 targets demonstrated that it is safe, is a potential treatment for these orphan diseases and appears to be a potent inflammation-resolving drug with a unique mechanism of action, distinct from the nonsteroidal anti-inflammatory drug (NSAID), and will be useful for treating a wide range of chronic inflammatory diseases.

MK-2748 is hepatitis C Virus NS3/4a Protease Inhibitor patented by pharmaceutical company Merck & Co Co for the treatment of hepatitis C virus infection.

Mitoglitazone (previously known as MSDC-0160 or CAY-10415) is a mTOT (mitochondrial target of thiazolidinediones) modulator that targets the mitochondrial pyruvate carrier (MPC), which is a key controller of cellular metabolism. MSDC-0160 is modulated MPC and act as insulin sensitizers without activating PPAR gamma. (Mitoglitazone exhibits very low binding affinity and activity at PPARγ). Mitoglitazone has been used in trials phase II studying the treatment of Type 2 Diabetes and Alzheimer's disease; the treatment for diabetes was discontinued. In addition, MSDC-0160 has demonstrated significant neuroprotective effects in the En1+/- mouse model of Parkinson’s disease via modulation of the mTOR-autophagy signaling cascade.

Pinometostat, also known as EPZ-5676, is a small molecule inhibitor of histone methyltransferase with potential antineoplastic activity. Upon intravenous administration, EPZ-5676 specifically blocks the activity of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic genes. Epizyme is developing pinometostat, a small molecule inhibitor of DOT1L, for the treatment of patients with MLL-r, a genetically defined acute leukemia. Epizyme is conducting a phase 1 clinical trial in pediatric patients. Epizyme is evaluating preclinical combinations of pinometostat with other anti-cancer agents in MLL-r leukemia. Pinometostat is being developed in collaboration with Celgene. Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the U.S.