hck-in-1

Hck-IN-1 is a selective Nef-dependent Hck inhibitor (IC50s: 2.8 μM and >20 μM for Nef:Hck complex and Hck) with antiretroviral activity. Hck-IN-1 is a direct and wide HIV-1 Nef antagonist with an IC50 of 100-300 nM for wild-type HIV-1 replication.

iHCK-37 (ASN05260065) is a selective Hck inhibitor with antitumor activity, blocking HIV-1 viral replication. iHCK-37 reduces PI3K/AKT and MAPK/ERK pathway activation after erythropoietin induction in high Hck-expressing cells, useful in chronic myelogenous leukemia (CML) research.

MRT-10350 (Compound 2) is a cereblon-based molecular glue degrader targeting HCK. This compound is applicable for research in diseases such as chronic myelogenous leukemia and HIV-1 infection.

SIK1-IN-1 (Compound 27) is a selective inhibitor of salt-inducible kinase 1 (SIK1) with an IC50 of 0.7 nM, demonstrating greater potency for SIK1 compared to SIK2 and SIK3. It shows no cytotoxicity in HEK293 cells and PBMC at concentrations up to 30 μM. Additionally, SIK1-IN-1 effectively inhibits 392 kinases, particularly tyrosine kinases such as FGR, HCK, and LYN.

Hck-IN-3 is an orally effective inhibitor targeting HCK with a KD of 3.92 μM. It suppresses the release of NO and exhibits an IC50 of 6.52 μM in RAW264.7 cells. Hck-IN-3 inhibits the release of TNF-α, IL-6, and IL-1β in a concentration-dependent manner. Additionally, it downregulates the protein expression of NLRP3, ASC, pro-caspase-1, and pro-IL-1β, also dependent on concentration. Hck-IN-3 is applicable for research into acute and non-injury related inflammatory diseases.

BT424, a specific HCK inhibitor, modulates macrophage activation and autophagy in vitro, and mitigates inflammation and renal fibrosis in the UUO model [1].

KIN-8194 is a dual inhibitor of HCK and BTK, effective when administered orally, displaying IC 50 values of 0.915 nM for HCK and <0.495 nM for BTK. It inhibits growth and disrupts integrin-mediated adhesion in BTKi-resistant mantle cell lymphoma (MCL). Additionally, KIN-8194 has shown efficacy in overcoming ibrutinib resistance, enhancing survival in TMD-8 ABC DLBCL xenografted mice [1] [2].

PP487 is a dual tyrosine kinase/PI(3)K inhibitor, exhibiting IC50 values of 0.017 μM, 0.072 μM, 0.004 μM, 0.01 μM, 0.55 μM, 0.22 μM, and < 0.01 μM against DNA-PK, mTOR, Hck, Src, EGFR, EphB4, and PDGFR, respectively. It is applicable in cancer research [1].