Btk Inhibitor

DPPY (compound 6) is a potent PTK inhibitor with IC₅₀ values of <10, <10, <10 nM for EGFR, BTK, JAK3, respectively. DPPY shows anti-proliferative activity against B-cell lymphoma cells. DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF).

BTK-IN-8 is a potent and selective peripheral covalent BTK inhibitor (IC₅₀=0.22 nM; K_d=0.91 nM). BTK-IN-8 has good whole blood CD69 cellular potency (IC₅₀=0.029 µM).

BTK-IN-9 is a reversible BTK inhibitors with potent antiproliferative activity in mantle cell lymphoma. BTK-IN-9 specifically disturbs mitochondrial membrane potential and increases reactive oxygen species level in Z138 cells. BTK-IN-9 also induces cell apoptosis in Z138 cells.

BTK-IN-44 (Compound 10) is a potent noncovalent inhibitor of Bruton’s tyrosine kinase (BTK) with an IC₅₀ value of 24.7 nM. BTK-IN-44 interferes with signaling pathways of B cell malignancies, showing antitumor effects in lymphoma cells. BTK-IN-44 is promising for research of B cell malignancies (such as lymphoma).

LPS-123 is a covalently irreversible BTK inhibitor with an IC₅₀ of < 5 nM. LPS-123 simultaneously inhibits the catalytic activity of BTK at Tyr551 and its self-activation at Tyr223. LPS-123 inhibits phosphorylation of the AKT/mTOR and MAPK signaling pathways, activation of PLCγ2, ERK1/2, p38, AKT, and mTOR, and blocks the production of CCL3 and CCL4 chemokines. LPS-123 exhibits significant anti-proliferative activity against various B-cell lymphoma cell lines and effectively induces apoptosis via a caspase-dependent pathway. LPS-123 also demonstrates significant antitumor activity in the OCI-Ly7 xenograft model. LPS-123 can be used for lymphoma research.

RN983 (Compound 1) is a highly selective Bruton's tyrosine kinase (Btk) inhibitor. RN983 inhibits IgG production in B-cells with an IC₅₀ of 2.5 nM and PGD2 production from mast cells with an IC₅₀ of 8.3 nM. RN983 is promising for research of asthma and other allergic diseases.

BTK-IN-49 is a selective, orally active and brain-penetrant BTK inhibitor with an IC₅₀ of 0.14 nM. BTK-IN-49 binds to BTK and blocks B-cell receptor and Fcγ receptor signaling. BTK-IN-49 inhibits the proliferation of CNS-compartmentalized B-cells and FcγR-induced microglial proliferation in a BTK-dependent manner. BTK-IN-49 can be used for the study of multiple sclerosis.

SRX3305 is an BTK/PI3K/BRD4 inhibitor with IC₅₀s of 6.5 nM, 15 nM, and 4 nM toward BTK, PI3Kɑ and PI3Kδ, respectively. SRX3305 attenuates chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) cell proliferation and promotes apoptosis in a dose-dependent fashion. SRX3305 yields potent anti-tumor effects but spares healthy bystander cells. SRX3305 inhibits the activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals. SRX3305 blocks CLL cell migration toward CXCL-12 and CXCL-13. SRX3305 maintains its anti-tumor effects in Ibrutinib (HY-10997)-resistant CLL cells. SRX3305 can be used for research in CLL, diffuse large B-cell lymphoma (DLBCL) and MCL.

BTK-IN-36 (S-016) is a BTK inhibitor, with IC₅₀ of 0.5 nM. BTK-IN-36 can be used in cancer-related research.

RET-IN-14 (compound 49) is a potent RET inhibitor with IC₅₀s of <0.51 nM, 9.3 nM, 1.3 nM, 9.2 nM, 15 nM for RET (WT), RET (G810R), RET (V804M), BTK and BTK (C481S), respectively. RET-IN-14 has the potential for tumors research

RSH-7 is a potent BTK and FLT3 inhibitor with IC₅₀s of 47, 12 nM, respectively. RSH-7 induces apoptosis and shows antiproliferative activities. RSH-7 inhibits BTK and FLT3 signaling and shows anti-tumor activity.

BTK-IN-15 (compound 42) is a potent Bruton's tyrosine kinase (BTK) inhibitor with high oral absorption. BTK-IN-15 inhibits BTK with an IC₅₀ value of 0.7 nM. BTK-IN-15 displays excellent kinase selectivity, antitumor activity, and induces apoptosis.

VA5 is a BTK kinaseinhibitor. VA5 has the potential to be used to study diseases associated with BTK kinase activity.

BTK-IN-38 (Example 125) is a potent BTK inhibitor. BTK-IN-38 inhibits DOHH2 and BT474 cells proliferation with IC₅₀s of 114 and 340 nM, respectively.

BTK-IN-46 (compound 24) is a reversible covalent BTK inhibitor. BTK-IN-46 covalently labels a lysine in the inositol phosphate (PIP3) binding site, thereby blocking Pleckstrin homology (PH) domain-mediated membrane recruitment and activation of BTK.

JAK3/BTK-IN-5 is a potent inhibitor of JAK3/BTK. BTK and JAK3 are two important targets for autoimmune diseases. Simultaneous inhibition of the BTK/JAK3 signalling pathway exhibits synergistic effects. JAK3/BTK-IN-5 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147953A1, example 35)

BTK-IN-48 is a BTK inhibitor with an IC₅₀ of 1.14 μM. BTK-IN-48 inhibits recombinant BTK and c-Src, and exerts moderate inhibitory effects on LCK, BMX/ETK, FLT3 and PIM1. BTK-IN-48 can be used in the research of B-cell malignancies and autoimmune diseases.

BTK-IN-23 is a BTK inhibitor (IC₅₀: 12.8 nM). BTK-IN-23 also inhibits BLX and BMX with IC₅₀s of 35.6 and 5.7 nM respectively. BTK-IN-23 shows improved kinase selectivity compared to Ibrutinib (HY-10997).

BTK-IN-43 (compound 9) is an inhibitor of BTK with an IC₅₀ value of 21.6 nM. BTK-IN-43 has oral activity.

HZ-A-005 is a potent, selective, and covalent Bruton’s tyrosine kinase (BTK) inhibitor. HZ-A-005 markedly decreases tumor growth in xenograft mouse models.