Lck 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.

Velzatinib (M4205) is a multi-target inhibitor for PDGFRB, PDGFRA, CSF1R, c-Kit, FLT3, and LCK, with an IC₅₀s of 2.6, 50, 5.5, 44, 141 and 141 nM, respectively. Velzatinib exhibits antitumor efficacy in xenograft mouse models.

PRT062607 (P505-15) Hydrochloride is an orally available Syk inhibitor (IC₅₀: 1 nM) that inhibits inflammation and induction Apoptosis. PRT062607 Hydrochloride exerts potent antitumor activity in tumor xenograft mouse models.

AZM475271 (M475271) is an orally active and selective Src kinase inhibitor. AZM475271 inhibits phosphorylation of c-Src kinase, Lck, c-yes (IC₅₀s = 0.01, 0.03, 0.08 μM, respectively). AZM475271 induces apoptosis. AZM475271 reduces tumor cell proliferation and migration in vitro and in vivo, and reduces microvessel density (MVD). AZM475271 inhibits tumor growth and metastasis. AZM475271 sensitizes tumor cells to the cytotoxic effects of Gemcitabine (HY-17026).

Lck-IN-6 (Compound 12g) is a Lck inhibitor with an IC₅₀ of 3 nM. Lck-IN-6 inhibits the production of IL-2. Lck-IN-6 can be used in the research of rheumatoid arthritis and inflammatory bowel disease.

WH-4-023 GMP is WH-4-023 (HY-12299) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. WH-4-023 (Dual LCK/SRC inhibitor) is a Lck/Src dual target inhibitor with functions in stem cell maintenance and differentiation regulation. WH-4-023 blocks epithelial-mesenchymal transition, supports the self-renewal of porcine embryonic stem cells, and inhibits their differentiation into mesoderm and endoderm. WH-4-023 is a key component of 3i/LAF medium, and enables the stable establishment and long-term maintenance of porcine pre-gastrulation epiblast stem cell lines. Removal of WH-4-023 reduces the expression of pluripotency factors in porcine and human extended pluripotent stem cells. WH-4-023 can be applied to relevant studies such as non-small cell lung cancer resistant to EGFR-TKIs.

SB 220025 is a reversible, orally active, cell-permeable, ATP-competitive and selective human p38 MAPK inhibitor (IC₅₀ = 60 nM). SB 220025 also inhibits p56^Lck and PKC with IC₅₀ values of 3.5 and 2.89 µM, respectively. SB 220025 inhibits the expression of IL-8 gene in response to globular adiponectin (gAd), reduces inflammatory cytokine production and inhibits angiogenesis. SB 220025 effectively prevents the progression of arthritis in a chronic inflammatory disease model and can be used in the study of inflammation.

Lck inhibitor 2 is a bisanilino pyrimidine-derived tyrosine kinase inhibitor targeting LCK, BTK, LYN, SYK and TXK, with a K_d value of 10 nM against TXK.

PRT062607 (P505-15) acetate is an orally available Syk inhibitor (IC₅₀: 1 nM) that inhibits inflammation and induction Apoptosis. PRT062607 acetate exerts potent antitumor activity in tumor xenograft mouse models..

Lck-IN-5 (example C10) is a potent and selective lymphocyte-specific protein tyrosine kinase (LCK) inhibitor. Lck-IN-5 selectively disrupts the interaction between the SH3 domain of LCK and the RK motif of CD3ε, thereby impairing LCK recruitment to the TCR. Lck-IN-5 modulates the activity of CD3ε-containing CAR and TRuC T cells, attenuating cytokine production and promoting a central-memory-like phenotype associated with enhanced persistence. Lck-IN-5 can be used for autoimmune diseases and graft-versus-host disease research.

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).

BMS-279700 is an orally active Src-family kinase p56Lck inhibitor. BMS-279700 can block the production of proinflammatory cytokines (IL-2 and TNFα). BMS-279700 can inhibit T cell proliferation. BMS-279700 can be used for the researches of inflammation and immunology.

Lck-IN-2 (compound 12a) is an inhibitor of Lymphocyte-specific protein tyrosine kinase (Lck) with IC₅₀ of 10.6 nM. Lck-IN-2 reveals efficacy in colon cancer cells with GI₅₀s of 0.24-1.26 μM. Lck-IN-2 exhibits an apoptotic effect in Colo201 cells.

BTK-IN-45 (Compound 6b) is a potent, reversible, and selective BTK inhibitor with an IC₅₀ of 1.14 μM. BTK-IN-45 also exhibits modest inhibition for LCK. BTK-IN-45 can be used in the research of cancers, including leukemia.

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.

N-Deshydroxyethyl Dasatinib-C3-NH2 is an Target Protein Ligand-Linker Conjugate that incorporates a ligand for LCK (HY-107447) and a PROTAC linker (HY-76667), which recruits E3 ligases. N-Deshydroxyethyl Dasatinib-C3-NH2 can be used for synthesis of PROTAC SJ11646 (HY-175281).

Aminogenistein is a p56^lck inhibitor with a 1.2 μM IC₅₀. Aminogenistein inhibits production of Aβ1-40 and Aβ1-42 peptides. Aminogenistein induces accumulation of APP-CTFα and APP-CTFβ, indicating γ-secretase cleavage inhibition. Aminogenistein can be used for the research of alzheimer's disease.

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.

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).