Anaplastic lymphoma kinase (ALK) Inhibitor

CM-118 is a potent and selective c-Met and ALK inhibitor. CM-118 inhibits the HGF-induced c-Met phosphorylation. CM-118 inhibits phosphorylation of ALK, EML4-ALKv1, ALK F1174L, and EMl4-ALKv1 L1196M, with respective IC₅₀ values 0.92, 1.25, 1.9, and 3.5 μM. CM-118 exhibits anticancer activity against cancers dependent on the c-Met or ALK oncogenic pathways.

ALK-IN-23 is a potent ALK inhibitor with IC₅₀ values of 1.6 nM, 0.71 nM and 1.3 nM for ALK^WT, ALK^L1196M and ALK^G1202R. ALK-IN-23 can block cell cycle in G2 phase and induce apoptosis. ALK-IN-23 inhibits cancer cell migration and colony formation in vitro. ALK-IN-23 exhibits antitumor activity in H2228 xenograft nude mice model with hypotoxicity.

ALK5-IN-84 (Compound 23) is an ALK5 inhibitor with a pK_i value of 9.35 against hALK5. When administered via inhalation, ALK5-IN-84 exhibits significant ALK5 inhibitory activity. ALK5-IN-84 is promising for the development of inhaled ALK5 inhibitors.

SMU-B is the orally active inhibitor for ALK (IC₅₀<0.5 nM), c-ros oncogene 1 (ROS1), c-MET (IC₅₀=1.87 nM) and AXL (IC₅₀=28.9 nM). SMU-B inhibits the proliferation of MKN45, H1993 and H441 with IC₅₀s of 0.02 μM, 1.58 μM and 2.82 μM, respectively. SMU-B exhibits antitumor efficacy in mouse models.

ConB-1 is a potent and selective ALK inhibitor with low toxicity to normal cells.

ALK/HDAC-IN-2 (Compound 19b) is an ALK/HDAC inhibitor with IC₅₀ values for ALK WT and total HDACs of 8 nM and 1.18 μM, respectively. ALK/HDAC-IN-2 exhibits inhibitory activity against ALK mutants G1202R, F1174L, and L1196M, with IC₅₀ values of 2.74, 9.23, and 34.28 nM, respectively. ALK/HDAC-IN-2 shows potent and selective inhibition against HDAC1 (IC₅₀ = 0.24 μM), while its inhibitory activity against HDAC7, HDAC6, and HDAC11 is weak (IC₅₀ > 10 μM). ALK/HDAC-IN-2 has broad-spectrum anti-proliferative activity against various cancer cells, inducing cell cycle arrest and apoptosis. ALK/HDAC-IN-2 can be used for the study of neuroblastoma.

(E)-Belizatinib ((E)-TSR-011)) (compound 36), the (E)-isomer of Belizatinib (HY-17603), is a potent, selective and orally active anaplastic lymphoma kinase (ALK) Inhibitor with an enzymatic IC₅₀ of 0.005 μM and a cellular IC₅₀ of 0.048 μM. (E)-Belizatinib shows >61-fold selectivity over JAK2, SRC, and IGF1R. (E)-Belizatinib shows favorable potency and PK characteristics in rats and dogs. (E)-Belizatinib can be used for ALK-driven cancer research.

Aurora kinase/ALK-IN-1 is a dual Aurora A kinase and ALK inhibitor with IC₅₀ values of 0.296 μM and 0.332 μM, respectively. Aurora kinase/ALK-IN-1 induces G₂/M cell cycle arrest, triggers mitochondrial apoptosis, elevates intracellular reactive oxygen species (ROS) levels, and inhibits ALDH1 activity. Aurora kinase/ALK-IN-1 demonstrates cytotoxicity and tumor selectivity. Aurora kinase/ALK-IN-1 can be used for the research of anaplastic large cell lymphoma.

ALK5-IN-86 (Compound 22f) is a selective ALK5 inhibitor with an IC₅₀ of 0.267 μM. ALK5-IN-86 forms hydrogen bonds with key amino acid residues in the active site of ALK5. ALK5-IN-86 is applicable to the research of diseases such as liver fibrosis.

ALK5-IN-79 (compound 57) is an ALK inhibitor with anticancer activity, by blocking TGF-β1/SMAD signaling pathway. ALK5-IN-79 attenuates the production of extracellular matrix (ECM) and deposition of collagen. ALK5-IN-79 exhibits adequate pharmacokinetic (PK) properties and good in vivo tolerance.

ALK/HDAC-IN-1 is a dual inhibitor for ALK and HDAC6, with IC₅₀s of 16 nM and 1.03 μM, respectively. ALK/HDAC-IN-1 exhibits antitumor activity.

2-Keto Crizotinib (PF-06260182) is an active lactam metabolite of crizotinib.

KRCA-0713 is an ALK inhibitor with anti-ALK activity. KRCA-0713 showed promising anti-ALK activity in enzyme and cell-based experiments. KRCA-0713 was shown to effectively inhibit ALK-driven tumor growth in H3122 xenograft model studies, similar to the effect of ceritinib.

ALK-IN-33 (Compound 8q) is an orally active ALK inhibitor with an IC₅₀ of 1.61 nM. ALK-IN-33 exhibits significant selective killing effect on ALK-positive cancer cells. ALK-IN-33 induces cell cycle arrest and apoptosis, effectively weakening the migration, invasion and long-term survival ability of cancer cells. ALK-IN-33 can be used for research on non-small cell lung cancer

ALK5-IN-26 (EX-22) is an ALK (Activin receptor-like kinase) inhibitor. ALK5-IN-26 inhibits ALK5 with an IC₅₀ value ≤10 nM. ALK5-IN-26 can be used for the research of cancer.

WZH-15-125 is a potent ALK inhibitor. WZH-15-125 can effectively overcome drug resistance, especially compound ALK mutations. WZH-15-125 has an IC₅₀ of 101.7 nM for the highly refractory G1202R/L1196M mutation that is resistant to Lorlatinib (HY-12215). WZH-15-125 can be used as a PROTAC target protein ligand to synthesize PROTAC WZH-17-002 (HY-174315). WZH-15-125 can be used in the research of non-small cell lung cancer.

ALK-IN-13 is an ALK inhibitor, extracted from patent US20130225528A1, example 19.

F6524-1593 is an ALK inhibitor. F6524-1593 has inhibitory activity against A549 and HepG-2 cells with IC₅₀ values of 161.1 μM and 91.03 μM, respectively. F6524-1593 can be used in the research of ALK-related cancers (such as non-small cell lung cancer, lymphoma and neuroblastoma).

KF-20444 is an orally active ALK inhibitor with blood-brain barrier penetration. KF-20444 exhibits strong inhibitory activity against ALK fusion proteins (EML4-ALK) and ALK resistance mutations (including L1196M, G1202R, and F1174L). KF-20444 effectively suppresses the phosphorylation of ALK in ALK-driven cancer cell lines, thereby inhibiting cancer cell proliferation and inducing apoptosis. KF-20444 demonstrates anti-tumor efficacy in mouse models bearing ALK-positive non-small cell lung cancer (NSCLC) or neuroblastoma. KF-20444 can be used for the study of ALK-driven malignancies.

CDD-1115 is a BMPR2 serine/threonine kinase inhibitor with an IC₅₀ of 1.8 nM against human BMPR2 kinase. CDD-1115 selectively inhibits the catalytic activity of BMPR2, and shows weak inhibitory effects on ALK1 and ALK2.