1H-1,4-Diazepine, hexahydro-1,4-bis((4E)-5-(3,4,5-trimethoxyphenyl)-4-penten-1-yl)-

K-7174 dihydrochloride is a small molecule inhibitor that has been extensively studied for its potential therapeutic applications in various diseases. It is a potent inhibitor of Rho-associated coiled-coil containing protein kinase (ROCK), which plays a crucial role in various cellular processes such as cell migration, proliferation, and apoptosis.

BIIB-057 is a potent inhibitor of the non-receptor tyrosine kinase Syk (IC50 = 1 nM). It displays at least 80-fold selectivity for Syk over other kinases. BIIB-057 blocks B cell receptor-mediated cell signaling and activation in whole blood (IC50s = 0.27 and 0.28 µM, respectively), as well as Fcɛ receptor 1-mediated basophil degranulation (IC50 = 0.15 µM). It antagonizes chemokine production, cell migration, and survival of chronic lymphocytic leukemia (CLL) cells after B cell receptor activation and synergistically enhances the action of fludarabine in killing CLL cells. BIIB-057 is orally bioavailable, as it produces dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. It also prevents splenomegaly and inhibits non-Hodgkin lymphoma tumor growth in a xenograft model.
PRT062607(P505-15; PRT-2607; BIIB-057) is a highly specific and potent inhibitor of Syk with IC50 of 1-2 nM; >80-fold selective for Syk than Fgr, Lyn, FAK, Pyk2 and Zap70. IC50 value: 1-2 nM Target:Syk kinase inhibitorin vitro: In human whole blood, P505-15 potently inhibited B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM). P505-15 successfully inhibited SYK-mediated B-cell receptor signaling and decreased cell viability in NHL and CLL. PRT318 and P505-15 effectively antagonize CLL cell survival after BCR triggering and in nurse-like cell-co-cultures. Moreover, they inhibit BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and beneath stromal cells. PRT318 and P505-15 furthermore inhibit Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering. in vivo: Similar levels of ex vivo inhibition were measured after dosing in mice (Syk signaling IC50 0.32 μM). Oral administration of P505-15 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. Oral dosing in mice prevented BCR-mediated splenomegaly and significantly inhibited NHL tumor growth in a xenograft model. In addition, combination treatment of primary CLL cells with P505-15 plus fludarabine produced synergistic enhancement of activity at nanomolar concentrations.

CFI400945 is a potent and selective,orally bioavailable PLK4 inhibitor with an IC50 value of 2.8 ±1.4 nM have potential antineoplastic activity.target: PLK4[1]IC50：2.8 ±1.4 nM [3]In vitro: Cancer cells treated with CFI-400945 exhibit effects consistent with PLK4 kinase inhibition, including dysregulated centriole duplication, mitotic defects, and cell death.[1] CFI-400945 treatment lead to aberrant centriole duplication and abnormal mitoses in vitro that ultimately causes cell death or cell-cycle arrest. [2]In vivo: Oral administration of CFI-400945 to mice bearing human cancer xenografts results in the significant inhibition of tumor growth at doses that are well tolerated.[1]Oral administration of CFI-400945 was well tolerated in multiple xenograft models and mouse strains, and had favorable pharmacokinetics. CFI-400945 also had single-agent antitumor activity.[2]

Safinamide is a drug used in the treatment of Parkinson's disease. It is a monoamine oxidase B (MAO-B) inhibitor that works by increasing the levels of dopamine in the brain. It was first approved by the European Medicines Agency (EMA) in 2015 and later by the US Food and Drug Administration (FDA) in 2017. This paper aims to provide a comprehensive review of safinamide, including its method of synthesis or extraction, chemical structure and biological activity, biological effects, applications, and future perspectives and challenges.