Fyn Inhibitor

GLPG3312 (Compound 28) is an orally active SIK inhibitor with IC₅₀ values of 2.0 nM, 0.7 nM and 0.6 nM for SIK1, SIK2 and SIK3, respectively. GLPG3312 exhibits anti-inflammatory and immunomodulatory activity in vitro on human primary myeloid cells and in vivo in mouse models. GLPG3312 has good oral bioavailability and can be used for research on inflammatory and immune diseases.

Papaveroline hydrochloride is an orally active Fyn tyrosine kinase inhibitor. Papaveroline hydrochloride stably binds to the active site of Fyn tyrosine kinase via hydrogen bonding and hydrophobic interactions, thereby inhibiting kinase activity associated with the pathogenesis of Alzheimer's disease. Papaveroline hydrochloride can be used for the research of Alzheimer's disease.

Papaveroline is a Fyn tyrosine kinase inhibitor, Na⁺,K⁺-ATPase inhibitor with an I50 of 0.20 mM, Mg²⁺-ATPase inhibitor, K⁺-activated pNPPase inhibitor with an I50 of 1.51 mM, and apoptosis inducer. Papaveroline binds to the active site of Fyn tyrosine kinase and forms stable interactions with pocket amino acid residues. Papaveroline induces cell apoptosis, produces pycnotic and fragmented cell nuclei, and does not reduce intracellular ATP levels. Papaveroline is a dopamine-derived neurotoxin candidate associated with the pathogenesis of Parkinson's disease. Papaveroline can be used in the research of Alzheimer's disease and Parkinson's disease.

RK-20448 is an ATP-competitive inhibitor of Lck, Src, KDR/VEGF2R and Tie-2 with IC₅₀ values of 0.24, 1.19, 10.74 and 5.85 µM, respectively. RK-20448 also inhibits BLK, Csk, Fyn and Lyn with IC₅₀ values of 0.37, 4.27, 2.03 and 0.43 µM, respectively. RK-20448 is the cis isomer of A-419259 (HY-15764).

ARN25699 is a kinase inhibitor with an IC₅₀ of 5.5 nM against GSK-3β, 2.2 nM against FYN-α, and 242.3 nM against DYRK1A, and it exhibits oral bioavailability. ARN25699 reduces hyperphosphorylation of tau protein and promotes microtubule bundle formation. ARN25699 has a broader kinome inhibitory profile and targets kinases associated with the pathogenic mechanisms linked to Alzheimer's disease. ARN25699 can be used in the research of Alzheimer's disease and related tauopathies.

Fyn-IN-1 (Compound 43) is a selective, blood-brain barrier permeable Fyn and GSK-3β inhibitor with IC₅₀ values of 0.044 μM and 0.61 μM, respectively. Fyn-IN-1 significantly downregulates the pro-inflammatory enzyme iNOS. Fyn-IN-1 can be used in the research of neurodegenerative diseases.

Antifibrotic agent 1 is an orally active anti-idiopathic pulmonary fibrosis (IPF) agent. Antifibrotic agent 1 effectively attenuates IPF-related processes, including TGF-β induced EMT and FMT processes, as well as pro-fibrotic M2 polarization. Antifibrotic agent 1 selectively inhibits CSF-1R, PDGFR-α and Src family kinases (SFKs), while sparing VEGFRs, FGFRs and Abl to minimize off-target toxicity. Antifibrotic agent 1 has potent anti-fibrotic activity in Bleomycin (BLM) (HY-108345)-induced pulmonary fibrosis mice model.

BMS-243117 is a potent, and selective benzothiazole based p56^Lck inhibitor with an IC₅₀ of 4 nM. BMS-243117 inhibits anti-CD3/anti-CD28 induced PBL (human peripheral blood T-cells) proliferation with an IC₅₀ of 1.1 μM. BMS-243117 binds in an extended conformation to the ATP-binding site of Lck.