Anaplastic lymphoma kinase (ALK) Inhibitor

ALKBH5-IN-5 is a highly selective ALKBH5 (IC₅₀ = 0.62 μM, K_d = 804 nM). ALKBH5-IN-5 disrupts ALKBH5 binding to m⁶A-RNA and 6mA-DNA substrates. ALKBH5-IN-5 promotes differentiation, induces apoptosis, cause G2-M phase arrest and exerts strong antiproliferative effects in cancer cells. ALKBH5-IN-5 reduces TACC3 and MYC protein levels and increases cleaved caspase-3 levels. ALKBH5-IN-5 exerts antitumor activity in tumor xenograft mice models. ALKBH5-IN-5 can be used for the research of acute myeloid leukemia.

GSK1838705A is a potent and reversible IGF-IR and the insulin receptor inhibitor with IC₅₀s of 2.0 and 1.6 nM, respectively. It also inhibits ALK with an IC₅₀ of 0.5 nM.

CAY10594 is an orally active PLD2 inhibitor with an IC₅₀ of 140 nM. CAY10594 has activities such as anti-tumor, anti-oxidation and liver protection. CAY10594 can be used for the research of diseases like breast cancer, acute liver injury and colitis.

CEP-37440 is a potent, orally active dual FAK/ALK inhibitor with IC₅₀ values of 2.3 nM and 3.5 nM for FAK and ALK, respectively. CEP-37440 decreases the cell proliferation by blocking the autophosphorylation kinase activity of FAK1 (Tyr 397).

CPD-1224 is an orally effective ALK inhibitor, a derivative of an ALK inhibitor that connects to the cereblon ligand. CPD-1224 targets the EML4-ALK oncogenic fusion protein and degrades both ALK and the mutant forms L1196M/G1202R. CPD-1224 can slow down tumor growth.

Ensartinib dihydrochloride (X-396 dihydrochloride) is a BBB-permeable and dual ALK/MET inhibitor with IC₅₀s of <0.4 nM and 0.74 nM, respectively.

A 83-01 (GMP) is A 83-01 (HY-10432) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. A 83-01 is a potent ALK4/5/7 inhibitor.

Iruplinalkib (WX-0593) is an orally active and selective ALK/ROS1 inhibitor. Iruplinalkib can effectively inhibit tyrosine autophosphorylation of ALK and mutant ALK, EGFR, with the IC₅₀ between 5.38 and 16.74 nM. Iruplinalkib is also a suppressive agent of the transporter MATE1, MATE2K, P-gp and BCRP. Iruplinalkib can be used in the study of non-small cell lung cancer.

5-O-Methylvisammioside (4'-O-β-D-Glucosyl-5-O-methylvisamminol) is an orally active natural chromone glycoside and multiple biological activities. 5-O-Methylvisammioside inhibits ferroptosis by activating the Nrf2/HO-1 signaling axis. 5-O-Methylvisammioside alleviates intestinal barrier damage by inhibiting the ROS/NF-κB/NLRP3 pathway. 5-O-Methylvisammioside exerts a protective effect against acute liver injury by reducing ALT/AST, decreasing inflammatory infiltration, and inhibiting IκB-α phosphorylation and NF-κB nuclear translocation. 5-O-Methylvisammioside blocks the HMGB1/RAGE/MEK/ERK signaling axis to exert anti-tumor and anti-angiogenic effects. 5-O-Methylvisammioside improves depression-like behaviors by inhibiting Src kinase and the NF-κB pathway.

M4K2234, a chemical probe, is an orally active, highly selective inhibitor of ALK1 and ALK2 with IC₅₀ values of 7 nM and 14 nM, respectively. M4K2234 specifically blocks BMP signaling by inhibiting the phosphorylation of SMAD1/5/8. M4K2234 inhibits BMP7-stimulated reporter gene activity (IC₅₀ = 16 nM). M4K2234 can be used for the investigation of ALK1/2-mediated biological processes and related diseases such as diffuse midline glioma (DMG) and fibrodysplasia ossificans progressiva (FOP).

Ascrinvacumab (PF-03446962) is a human IgG2 monoclonal antibody targets ALK-1. Ascrinvacumab shows binding efficiency with human ALK1 with a K_d value of 7 nM. Ascrinvacumab can be used for the research of hepatocellular carcinoma (HCC).

Zotizalkib (TPX-0131) is a potent, selective, CNS-penetrant and orally active inhibitor of wild-type ALK (IC₅₀ of 1.4 nM) and ALK-resistant mutation, e.g. G1202R (IC₅₀ of 0.3 nM), L1196M (IC₅₀ of 0.3 nM). Zotizalkib has strong antitumor activities.

XST-14 is a potent, competitive and highly selective ULK1 inhibitor with an IC₅₀ of 26.6 nM. XST-14 induces autophagy inhibition by reducing the phosphorylation of the ULK1 downstream substrate. XST-14 induces apoptosis in hepatocellular carcinoma (HCC) cells and has antitumor effects.

Tosposertib (TU2218 free base) is an ALK5/VEGFR2 dual inhibitor (IC₅₀ = 1.2 nM/4.9 nM). Tosposertib directly restores the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFβ and suppresses the activity and viability of regulatory T cells. Tosposertib can be used for the study of melanoma and colon cancer.

W23-1006 is a selective and covalent ALKBH5 inhibitor. W23-1006 binds to the ALKBH5 C200 residue with an IC₅₀ value of 3.848 μM. W23-1006 shows ~30- and 8-fold stronger inhibitory activity than that against FTO and ALKBH3, respectively. W23-1006 can be used for the study of triple-negative breast cancer (TNBC).

Belizatinib (TSR-011) is an orally active, potent inhibitor of ALK and TRKA, TRKB, and TRKC, with IC₅₀ of 0.7 nM for wild-type recombinant ALK kinase.

ALK-IN-1 is an orally active, blood-brain barrier-permeable ALK and EGFR inhibitor. ALK-IN-1 binds to and inhibits ALK kinase, ALK fusion proteins, and wild-type and mutant EGFR variants, thereby disrupting their corresponding signaling pathways. ALK-IN-1 can suppress the growth and proliferation of tumor cells and exhibits potential inhibitory activity against mutant EGFR. ALK-IN-1 can be used in the research of non-small-cell lung cancer.

CEP-28122 mesylate salt, a diaminopyrimidine derivative, is a potent, selective, and orally active ALK inhibitor with an IC₅₀ value of 1.9 nM. CEP-28122 mesylate salt has antitumor activity in experimental models of ALK-positive human cancers. CEP-28122 mesylate salt has good pharmacodynamic and pharmacokinetic activity. CEP-28122 mesylate salt can be used for the study of ALK-positive anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), and neuroblastoma cells.

Itacnosertib (TP-0184) is the inhibitor for FLT3, ACVR1 (ALK2, IC₅₀=8 nM) and JAK2 (IC₅₀=8540 nM). Itacnosertib exhibits anti-leukemic activity.

APG-2449 is an orally active inhibitor for BCL-2 and multikinase (ALK/FAK/ROS1) with potent antitumor activities. APG-2449 reduces cell viability and enhances apoptosis in acute myeloid leukemia cells in vitro. APG-2449 decreases activation of FAK and its downstream effectors. APG-2449 can be studied in research for mesothelioma tumor, non-small cell lung cancer, ovarian cancer, hematologic and solid malignancies.