CH5183284/Debio 1347 is selective and orally available fibroblast growth factor receptors: FGFR1, FGFR2, and FGFR3 inhibitor that has a unique chemical scaffold. By interacting with unique residues in the ATP-binding site of FGFR1, FGFR2, or FGFR3, CH5183284/Debio 1347 selectively inhibits there receptors, but does not inhibit kinase insert domain receptor (KDR) or other kinases. CH5183284/Debio 1347 will provide therapeutic opportunities for patients who have FGFR genetic alterations and patients with acquired resistance to existing FGFR selective inhibitors that contain the common methoxy moieties.

Bristol-Myers Squibb developed BMS-394136, as a selective IKur inhibitor for the treatment of arrhythmias. IKur is a repolarizing K+ current encoded by the KCNA5 gene and is expressed predominantly in the atrium of human. IKur is a potential atrial-selective target for the treatment of atrial fibrillation. Atrial selectivity and safety of BMS-394136 were studied in phase I clinical trial in patients with heart diseases. However, further, development has been discontinued.

Puerarin (7, 4’-dihydroxyisolavone-8-β-glucopyranoside) is an active isoflavone extracted from the roots of Pueraria lobata (Willd.) Ohwi. Puerarin is widely used in traditional Chinese medicine, and is clinically used in China for the treatment of coronary artery disease, heart failure, hypertension and myocardial infarction. It has been reported that puerarin had therapeutic effects on diabetes mellitus, arteriosclerosis and myocardial ischemia in animals. Puerarin demonstrated beta-adrenergic receptor blocking effect. On the other hand, puerarin stimulated alpha1-adrenoreceptor to increase glucose uptake into cultured C2C12 cells of mice. Puerarin has been investigated for the treatment (phase II clinical trials) of Alcohol Abuse, Rheumatoid Arthritis and Hypertension.

Apitolisib, a dual inhibitor of mTOR and phosphatidylinositol 3-kinase (PI3K), was being developed by Roche and Genentech as an orally administered therapy of cancer. Apitolisib is a selective, potent, orally bioavailable inhibitor of Class I PI3 kinase (PI3K) and mTOR kinase (TORC1/2) with excellent pharmacokinetic and pharmaceutical properties. Apitolisib displayed excellent potency against class I PI3K isoforms (IC50 PI3K-α, β, δ and γ = 4.8, 27, 6.7 and 14 nM) and mTOR kinase (IC50 = 17 nM) and selectivity against a large panel of other kinases. Apitolisib is in phase II trials by Genentech for the treatment of breast cancer, prostate cancer, endometrium cancer, kidney cancer. However, no recent development has been reported. It is also in phase I trials by Genentech for the treatment of non-Hodgkin's lymphoma.

Napsagatran [RO 466240], a reversible and highly selective thrombin inhibitor, was in development with Roche for use in myocardial infarction and thrombosis. Napsagatran efficiently inhibits and delays thrombin generation in human coagulating plasma. This reduced thrombin generation might be caused by inhibition of thrombin-mediated feedback reactions during blood coagulation. Ro 46-6240 inhibited clot-bound thrombin three times more potently than fluid-phase thrombin (IC50 19 vs 56 ng/ml) while hirudin was two times (IC50 8 vs 3 ng/ml) and heparin six times (IC50 1,205 vs 200 ng/ml) less active against clot-bound thrombin compared with fluid-phase thrombin.

FERMAGATE is a phosphate binder with phosphate plasma levels lowering activity. It is in Phase 3 development in the US and in Europe for the treatment of hyperphosphatemia in dialysis patients. It is made up of magnesium and ferric iron atoms held in an insoluble, rigid, crystalline-layered structure, with carbonate groups lying between the layers. Upon oral administration, the carbonate ions in FERMAGATE are exchanged for free phosphate ions released from food in the gastrointestinal tract; thereby, strongly binding phosphate. This inhibits phosphate uptake and preventing hyperphosphatemia.