Hck 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.

Hck-IN-3 (compound 2D) is an orally effective inhibitor targeting HCK (K_D = 3.92 μM). Hck-IN-3 can inhibit the release of NO. Hck-IN-3 has an IC₅₀ of 6.52 μM in RAW264.7 cells. Hck-IN-3 can inhibit the release of TNF-α, IL-6, and IL-1β in a concentration dependent manner. Hck-IN-3 downregulates the protein expression of NLRP3, ASC, pro-caspase-1, and pro-IL-1β in a concentration dependent manner. Hck-IN-3 can be used for research on acute non traumatic inflammatory conditions.

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.

SIK1-IN-1 (Compound 27) is a selective Salt-inducible kinase 1 (SIK1) inhibitor with an IC₅₀ of 0.7  nM for SIK1 over SIK2 and SIK3. SIK1-IN-1 has no cytotoxicity against HEK293 cells and PBMCs (maximum concentration of 30 μM). SIK1-IN-1 also has potent inhibitory activities for 392 kinases, in particular tyrosine kinases, such as FGR, HCK and LYN).