Bcr-Abl Inhibitor

Ponatinib hydrochloride (AP24534 hydrochloride) is a hydrochloride of ponatinib. Ponatinib is an orally active multi-targeted kinase inhibitor with IC₅₀s of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively.

Flumatinib (HHGV678) is an orally available, selective inhibitor of Bcr-Abl. Flumatinib inhibits c-Abl, PDGFRβ and c-Kit with IC₅₀s of 1.2 nM, 307.6 nM and 665.5 nM, respectively.

PD173952 is a tyrosine kinases inhibitor with IC₅₀s of 0.3, 1.7 and 6.6 nM against Lyn, Abl and Csk, respectively. PD173952 is also a potent Myt1 kinase inhibitor with a K_i of 8.1 nM. PD173952 induces apoptosis.

AST 487 is a RET kinase inhibitor with IC₅₀ of 880 nM, inhibits RET autophosphorylation and activation of downstream effectors, also inhibits Flt-3 with IC₅₀ of 520 nM.

KW-2478 is an HSP90 inhibitor (IC₅₀ = 3.8 nM). KW-2478 inhibits the growth and induces apoptosis in chronic myeloid leukemia (CML) cells and liver cancer cells. KW-2478 weakens the BCR/ABL and MAPK signaling pathways, leading to increased p27 and p21 expression and decreased cyclin B1 expression. KW-2478 downregulates STAT3 expression. KW-2478 may be used in research on cancers such as CML and liver cancer.

Dasatinib (BMS-354825) monohydrate 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 monohydrate inhibits Bcr-Abl and Src with IC₅₀s of <1.0 nM and 0.5 nM, respectively. Dasatinib monohydrate also induces apoptosis and autophagy.

PD166326 is an orally active tyrosine kinase inhibitor with a IC₅₀ of 8 nM against abl tyrosine kinase and a IC₅₀ of 6 nM against src tyrosine kinase. PD166326 blocks Bcr/Abl kinase activity. PD166326 inhibits Bcr/Abl-dependent proliferation and cell cycle progression. PD166326 reduces peripheral blood granulocytosis, alleviates splenomegaly and prolongs survival in a mouse model of chronic myeloid leukemia. PD166326 can be used in research related to chronic myeloid leukemia.

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

GNF-2 is a highly selective, allosteric, non-ATP competitive inhibitor of Bcr-Abl. GNF-2 inhibits Ba/F3.p210 proliferation with an IC₅₀ of 138 nM .

Vodobatinib (K0706) is a potent, third generation and orally active Bcr-Abl1 tyrosine kinase inhibitor with an IC₅₀ of 7 nM. Vodobatinib exhibits activity against most BCR-ABL1 point mutants, and has no activity against BCR-ABL1T315I. Vodobatinib can be used for chronic myeloid leukemia (CML) research. Vodobatinib is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Risvodetinib (IkT-148009) is an orally active, selective and brain-penetrant protein tyrosine kinase inhibitor, displaying excellent target efficacy against c-Abl1, c-Abl2/Arg with IC₅₀ values of 33 nM, 14 nM, respectively. Risvodetinib suppresses c-Abl activation and substantially protects dopaminergic neurons from degeneration in mouse models of both inherited and sporadic Parkinson’s disease (PD), which is promising for research in the field of PD.

GMB-475 is a potent BCR-ABL1 PROTAC based on Von Hippel-Lindau (VHL). GMB-475 targets the nutmeg pocket of ABL1 in an ectopic manner and degrades BCR-ABL1 protein through the ubiquitin proteasome pathway. GMB-475 inhibits the proliferation of human K562 cells and mouse Ba/F3 cells, and is used for the study of chronic myeloid leukemia.

Olverembatinib (GZD824) dimesylate is a potent and orally active pan-Bcr-Abl inhibitor. Olverembatinib dimesylate potently inhibits a broad spectrum of Bcr-Abl mutants. Olverembatinib dimesylate strongly inhibits native Bcr-Abl and Bcr-Abl^T315I with IC₅₀s of 0.34 nM and 0.68 nM, respectively. Olverembatinib dimesylate has antitumor activity. Olverembatinib (dimesylate) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Cenisertib (AS-703569) is an ATP-competitive multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5 and FLT3. Cenisertib induces major growth-inhibitory effects by blocking the activity of several different molecular targets in neoplastic mast cells (MC). Cenisertib inhibits tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia.

GNF-5, the N-hydroxyethyl carboxamide analog of GNF-2, is an orally active Bcr-Abl inhibitor. GNF-5 has Bcr-Abl inhibition activity with an IC₅₀ value of 0.22 µM. GNF-5 has good favorable pharmacokinetic properties. GNF-5 can be used for the research of kinds of cancer including chronic myelogenous leukemia (CML) and breast cancer.

Dasatinib metabolite M6 (Dasatinib carboxylic acid) is a circulating metabolite of Dasatinib (HY-10181). Dasatinib exhibits potent anti-tumor activity.

SIAIS178 is a potent and selective BCR-ABL degrader based on PROTAC technology with an IC₅₀ of 24 nM. SIAIS178 causes effective degradation of BCR-ABL protein by recruiting Von Hippel-Lindau (VHL) E3 ubiquitin ligase. SIAIS178 has anticancer activity.

Dasatinib-d₈ (BMS-354825-d₈) is a deuterium labeled Dasatinib. Dasatinib is a dual Bcr-Abl and Src family tyrosine kinase inhibitor.

GNF-7 is a multikinase inhibitor. GNF-7 is a Bcr-Abl inhibitor, with IC₅₀s of 133 nM and 61 nM for Bcr-Abl^WT and Bcr-Abl^T315I, respectively. GNF-7 also possesses inhibitory activity against both ACK1 (activated CDC42 kinase 1) and GCK (germinal center kinase) with IC₅₀s of 25 nM and 8 nM, respectively. GNF-7 can be used for the research of hematologic malignancies.

Bosutinib hydrate is an oraly activel Src/Abl tyrosine kinase inhibito with IC₅₀ of 1.2 nM and 1 nM, respectively.