Icosabutate (also known as PRC-4016 or NST-4016), a cholesterol ester transfer protein inhibitor was developed by NorthSea Therapeutics for the treatment of combined dyslipidemias and hypertriglyceridemia. Icosabutate successfully completed phase II clinical trial for hypertriglyceridemic subjects, where was studied the drug efficacy and safety. In April 2018 NorthSea Therapeutics announced that its lead product, icosabutate would be further developed as an effective and safe therapeutic approach to treating both non-alcoholic steatohepatitis and its associated comorbidities.

JNJ-38877605 is an orally available, small molecule inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor JNJ-38877605 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. JNJ-38877605 was in Phase I clinical trials. Combined clinical and correlative preclinical studies suggest that renal toxicity of JNJ-38877605 is caused by the formation of species-specific insoluble metabolites. These observations preclude further clinical development of JNJ-38877605.

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.

Rosiptor (AQX-1125) is a once daily, orally administered small molecule being developed by Aquinox Pharmaceuticals for the treatment of asthma, bladder pain syndrome/interstitial cystitis (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome. AQX-1125 is the only clinical-stage, orally administered, SHIP1 activator. AQX-1125 significantly reduces the late response to allergen challenge, with a trend to reduce airway inflammation. AQX-1125 was safe and well tolerated and merits further investigation in inflammatory disorders. AQX-1125 has been used in trials studying the treatment of COPD, atopic dermatitis, interstitial cystitis, and bladder pain syndrome. However, the development has been discontinued.

SB-203580 was originally prepared as inflammatory cytokine synthesis inhibitor that subsequently was found to be selective inhibitor of p38 MAP kinase. SB-203580 is a p38 MAPK inhibitor with IC50 of 0.3-0.5 uM in THP-1 cells, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 uM. SB203580 induces autophagy in human hepatocellular carcinoma (HCC) cells. Development of SB-203580 for cancer; postmenopausal osteoporosis; rheumatoid arthritis; septic shock has been discontinued.

Acoziborole (previously known as SCYX-7158) is a product of Anacor’s novel boron chemistry, which has produced a number of compounds with efficacy against a range of fungal, inflammatory, and bacterial diseases. Acoziborole was developed as an orally active compound with potent antitrypanosoma activity for the potential treatment of stage 2 human African trypanosomiasis (HAT) or sleeping sickness, a deadly parasitic disease transmitted by the tsetse fly. HAT is an important public health problem in sub-Saharan Africa. Existing therapies suffer from poor safety profiles, difficult treatment regimens, limited effectiveness, and a high cost of goods. Acoziborole is participating in phase II/III clinical trial to study its efficacy and safety in patients infected by HAT due to T.b. Gambiense.

TD139 is a highly potent, specific inhibitor of the galactoside binding pocket of galectin-3. TD139 is formulated for inhalation, which enables direct targeting the fibrotic tissue in the lungs, while minimizing systemic exposure. TD139 was initially developed by a team of scientists from Lund University, Sweden, and Edinburgh University, the UK. TD-139 is in phase I/II clinical trials for the treatment of idiopathic pulmonary fibrosis.