Bcr-Abl Inhibitor

SNIPER(ABL)-013, conjugating GNF5 (ABL inhibitor) to Bestatin (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC₅₀ of 20 μM.

SNIPER(ABL)-019, conjugating Dasatinib (ABL inhibitor) to MV-1 (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC₅₀ of 0.3 μM.

Rebastinib tosylate (DCC-2036 tosylate) is an orally active, non-ATP-competitive Bcr-Abl inhibitor, with IC₅₀ values of 0.8 nM and 4 nM against Abl1^WT and Abl1^T315I, respectively. Rebastinib tosylate potently inhibits CYP2C8 (IC₅₀ = 0.0533 μM) and CYP2C9 (IC₅₀ = 2.54 μM). Rebastinib tosylate allosterically inhibits Tie2 with an IC₅₀ of 0.63 nM. Rebastinib tosylate inhibits the transcriptional activity of FoxO1. Rebastinib tosylate inhibits SRC family kinases, KDR and FLT3 kinases. Rebastinib tosylate induces Apoptosis. Rebastinib tosylate exerts anti-tumor activity in breast cancer. Rebastinib tosylate exerts anti-angiogenic effects. Rebastinib tosylate increases myotube diameter and improves reduced contractility. Rebastinib tosylate can be used in research related to triple-negative breast cancer, luminal breast cancer, pancreatic neuroendocrine tumors, muscle atrophy, cancer cachexia, chronic myeloid leukemia, and B-lymphocytic leukemia.

Relcobatinib (Relcobatinibum) is a ABL1 kinase inhibitor with an IC₅₀ of 12.7 nM against wild-type ABL1 and an IC₅₀ of 43.5 nM against the ABL1^T315I mutant. Relcobatinib inhibits the phosphorylation of CRKL. Relcobatinib exhibits anticancer activity against chronic myeloid leukemia. Relcobatinib can be used in studies related to chronic myeloid leukemia.

SNIPER(ABL)-058, conjugating Imatinib (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC₅₀ of 10 μM.

SNIPER(ABL)-015, conjugating GNF5 (ABL inhibitor) to MV-1 (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC₅₀ of 5 μM .

SNIPER(ABL)-049, conjugating Imatinib (ABL inhibitor) to Bestatin (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC₅₀ of 100 μM.

c-ABL-IN-1 is a novel selective c-Abl inhibitor that prevents neurodegeneration in parkinson’s disease.

DA5-HTL is a compound combined dasatinib with HaloTag system efficiently inhibits the growth of the cancer cells with GI₅₀ of 1.923 nM.

EphB4-IN-1 is a selective EphB4 tyrosine kinase inhibitor with IC₅₀ values of 0.16-0.30 μM. EphB4-IN-1 binds to the ATP binding site of EphB4 in a DFG-in conformation, forming four stable intermolecular hydrogen bonds. EphB4-IN-1 also inhibits Src, Abl1, Lck, and EGFR kinases. EphB4-IN-1 inhibits EphB4 autophosphorylation. EphB4-IN-1 can be used for the research of cancer, such as non small cell lung cancer.

EAPB0503 is a quinoline compound with anti-tumor activity, showing strong cytotoxicity against melanoma cells in vitro (IC₅₀=200 nM). EAPB0503 can induce specific cell cycle arrest in mitosis of CML cells and directly activate apoptosis, leading to an increase in the G0 cell population, disruption of mitochondrial membrane potential, PARP cleavage, and DNA fragmentation. EAPB0503 also reduces the levels of BCR-ABL protein .

AP 24149 is a potent Src-Abl dual inhibitor with IC₅₀ values of 9.1, 3.6 nM for Src and Abl, respectively.

DosatiLink-1 is an Abelson murine leukemia (ABL) enzyme inhibitor.

Antiproliferative agent-30 (Compound 8g) inhibits tubulin assembly and inhibits FLT3 and Abl1. Antiproliferative agent-30 has vascular-disrupting activity. Antiproliferative agent-30 has broad antiproliferative activities against cancer cell lines (IC₅₀s: 0.054 nM, 0.008 nM, 0.144 nM for HCT-116, K562, MV-4-11 cells respectively). Antiproliferative agent-30 also has anticancer effect against AML with FLT3-ITD-TKD mutation.

Dasatinib (GMP Like) (BMS-354825 (GMP Like)) is Dasatinib (HY-10181) produced by using GMP like guidelines. GMP Like small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. Dasatinib (BMS-354825) is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The K_is are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib inhibits Bcr-Abl and Src with IC₅₀s of <1.0 nM and 0.5 nM, respectively. Dasatinib also induces apoptosis and autophagy.

Multi-kinase-IN-15 is an orally active multi-kinase inhibitor. Multi-kinase-IN-15 inhibits the kinase activity of MNK1, MNK2, ABL1, ABL1 T315I, FLT3, VEGFR2, RET, cKIT, FGFR2, PDGFRα, and PDGFRβ. Multi-kinase-IN-15 dose-dependently reduces phosphorylation of eIF4E and phosphorylated Crkl in tumor cells, and decreases phosphorylation of eIF4E in tumor tissues. Multi-kinase-IN-15 inhibits tumor growth. Multi-kinase-IN-15 can be used for research on chronic myeloid leukemia.

FLT3-ITD/D835Y-IN-1 (Compound 1) is a FLT3-ITD and BCR-ABL inhibitor. FLT3-ITD/D835Y-IN-1 mediates proapoptosis by inhibiting the FLT3 and BCR-ABL pathways, as well as other possible targets. FLT3-ITD/D835Y-IN-1 can be used in the study of acute myeloid leukemia (AML).

Asciminib-d₄ (ABL001-d₄) is the deuterated-labeled Asciminib (HY-104010). Asciminib (ABL001) is a potent and selective allosteric BCR-ABL1 inhibitor, which inhibits Ba/F3 cells grown with an IC₅₀ of 0.25 nM.

FGFRs-IN-1 (Compound A16) is the orally active inhibitor for FGFR, that inhibits FGFR1/2/3/4 with IC₅₀s of 2.3, 7, 11, and 163 nM, respectively. FGFRs-IN-1 also inhibits VEGFR1/2/3, Abl, and Flt3 with IC₅₀s of 61, 176, 112, 26, and 353 nM, respectively. FGFRs-IN-1 exhibits weak inhibitory efficacy against CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and inhibits epithelial-mesenchymal transition (EMT) in TGF-β1 stimulated A549 cell. FGFRs-IN-1 exhibits anti-inflammatory activity in Bleomycin (HY-17565)-induced mouse pulmonary fibrosis model and CCl₄ (HY-Y0298)-induced mouse liver fibrosis model.

cSRC/BCR-ABL-IN-1 (compound 21b) is a potent Bcr-Abl and C-Src inhibitor with IC₅₀ values of 56.2, 101 nM for Bcr-Abl, C-Src, respectively. cSRC/BCR-ABL-IN-1 shows cytotoxicity activity.