AZD9164 was invented by AstraZeneca as a muscarinic M(3) receptor antagonist for evaluation of the potential as a treatment for chronic obstructive pulmonary disease. However, in 2010 studies were discontinued.

LY2300559 is a dual metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator and cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. Eli Lilly was developing LY2300559 for the prevention of migraine. LY2300559 development has been discontinued.

CHF6001 is a phosphodiesterase 4 (PDE4) inhibitor optimised for inhaled delivery and tolerability, for the treatment of Asthma and Chronic Obstructive Pulmonary Disease. CHF6001 was 7- and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity. CHF6001 inhibited PDE4 isoforms A-D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site and displayed >20,000-fold selectivity versus PDE4 compared with a panel of phosphodiesterases. CHF6001 effectively inhibited the release of tumor necrosis factor-α from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). CHF6001 has the potential to be an effective topical treatment of conditions associated with pulmonary inflammation, including asthma and chronic obstructive pulmonary disease.

Sitravatinib (MGCD516) is a receptor tyrosine kinases (RTK) inhibitor that blocks a wide array of RTKs known to be amplified/overexpressed in sarcomas, which are key regulators of signaling pathways that lead to cell growth, survival and tumor progression. It is involved in driving sarcoma cell growth with IC50 of 3980 nM and is superior to other multi-kinase inhibitors in inhibiting cell proliferation, RTK phosphorylation, and phosphorylation of downstream effectors. The efficacy of sitravatinib was tested using a wide panel of sarcoma cell lines, including malignant peripheral nerve sheath tumor (MPNST), Ewing sarcoma (A673), osteosarcoma (Saos2), and liposarcoma (DDLS, LS141). Both in vitro and in vivo efficacy sitravatinib was significantly better that the other two multi-kinase inhibitors, imatinib and crizotinib. Sitravatinib treatment not only inhibits tumor cell proliferation at low nanomolar concentrations in vitro but also results significant tumor growth suppression in vivo in mouse xenograft models. Sitravatinib is being evaluated in a Phase 1b dose expansion cohort in selected patients with specific genetic alterations that are drivers of tumor growth, with an initial focus on Non-Small-Cell Lung carcinoma (NSCLC) and in other solid tumors where sitravatinib may confer a benefit. Its efficacy and safety is also being tested in Phase II clinical trials in patients with advanced liposarcoma as a monotherapy and NSCLC in combination with nivolumab.

MK-0359 (L-454560) is a selective and potent type 4 phosphodiesterases (PDE4) inhibitor, which binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. This compound successfully has passed the phase II clinical trial for the treatment of asthma, Pulmonary Disease, Chronic Obstructive (COPD) and Rheumatoid Arthritis. However, there is no information about the further research of this drug.

ATB-346, being developed by Antibe Therapeutics, a Toronto-based pharmaceutical company, is a hydrogen sulfide-releasing non-steroidal anti-inflammatory drug (NSAID) that inhibits COX and suppresses prostaglandin production. ATB-346 exhibits anti-inflammatory, analgesic, antinociceptive, immunomodulatory, and neuroprotective activities. In vivo, this compound attenuates zymosan-induced inflammation, nociception, and immune signaling. ATB-346 also prevents ligature-induced periodontal bone loss and pathologies, potentially by suppressing increases in pro-inflammatory cytokine levels. Additionally, ATB-346 decreases edema and improves neurological function in animal models of traumatic brain injury (TBI). ATB-346 completed Phase 1 clinical studies in Q1 2015. To better understand the metabolism of ATB-346, Antibe conducted a radiolabeled study in rats at Covance Laboratories that was completed in Q4 2015. Antibe received approval from Health Canada in March 2016 to conduct a Phase 2 trial of ATB-346 in patients with osteoarthritis of the knee. Preclinical studies of ATB-346 for the treatment intestinal cancer; malignant melanoma; periodontal disorders are in progress.

CE-326597 is a potent and selective agonist of type 1 cholecystokinin receptor, developed by Pfizer Inc for the treatment of obesity. The physical properties of CE-326597 provided the desired low systemic exposure which was driven by poor absorption of the drug into the intestinal wall. Unfortunately, CE-326597 demonstrated insufficient efficacy for the treatment of either diabetes or obesity after 12 weeks of dosing in Phase 2 clinical trial and was discontinued.

Ralinepag is a cyclohexyl amide derivative patented by Arena Pharmaceuticals, Inc. as agonists of the human prostacyclin (PGI2) receptor useful for the treatment of pulmonary arterial hypertension. Ralinepag shows selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30-50-fold selectivity over the EP3 receptor. Ralinepag had an excellent PK profile across species. Enterohepatic recirculation most probably contributes to a concentration-time profile after oral administration in the cynomolgus monkey that showed a very low peak-to-trough ratio. Phase III clinical trial is currently ongoing.