Bcr-Abl Inhibitor

CSF1R/c-Kit-IN-2 is a dual CSF-1R/c-Kit inhibitor with a c-Kit-biased profile, exhibiting inhibitory activity against CSF-1R (IC₅₀ = 6.84 nM), c-Kit (IC₅₀ = 0.95 nM), FYN (IC₅₀ = 11.4 nM), ABL1 (IC₅₀ = 14.2 nM), and CSK (IC₅₀ = 118 nM). CSF1R/c-Kit-IN-2 can be used for the research of neuroinflammation-associated neurodegenerative diseases.

WB-BC-15 (WGB-BC-15) is a c-Abl kinase inhibitor. WB-BC-15 can increase radiation-induced germ-cell apoptosis, with EC₅₀ of 10.5 μM.

AK-HW-90 (compound 2B) is a potent panBcr-Abl inhibitor with significant inhibitory activity against Imatinib (HY-15463)-resistant mutants. AK-HW-90 inhibits the resistance mutant Bcr-Abl^T315I with an IC₅₀ of 0.65 nM. AK-HW-90 has potential anticancer activity and can be used in the study of chronic myelogenous leukemia (CML).

AP24163 is a BCR-ABL kinase inhibitor. AP24163 inhibits wild-type (native) BCR-ABL and BCR-ABL-T315I with IC₅₀ values of 7 nM and 511 nM, respectively. AP24163 can be used in the research of chronic myeloid leukemia (CML).

BCR-ABL1-IN-2 (compound 8) is a potent BCR-ABL1 tyrosine kinase inhibitor. BCR-ABL1-IN-2 exhibits activity in Imatinib (HY-15463) resistant K562/DOX cells with LC₅₀ of 5.29 μM. BCR-ABL1-IN-2 shows no significant toxicity in nontumor cells. BCR-ABL1-IN-2 can be used for chronic myeloid leukemia research.

c-ABL-IN-3 is a potent inhibitor of c-Abl. Activation of c-Abl has been implicated in various diseases, notably cancer. c-ABL-IN-3 has the potential for the research of neurodegenerative diseases (amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) and cancer (extracted from patent WO2021048567A1, compound 50).

PD173956 is a pyridopyrimidine Bcr-Abl kinase inhibitor with high selectivity for the P-loop mutant form of Bcr-Abl.

AP-24567 is a Ligands for Target Protein for PROTAC, which can be used for the synthesis of SB1-G-187 (HY-137342).

HPK1-IN-61 (Compound 1) is an inhibitor of hematopoietic progenitor kinase 1 (HPK1) (K_i = 0.4 nM) and an inhibitor of Abl (IC₅₀ < 0.51 nM). HPK1-IN-61 also shows inhibitory activity against LCK with an IC₅₀ of 24 nM.

3'-BPANeuGc is a high-affinity selective Siglec-G ligand. Lipid nanoparticles surface-modified with antigens and 3'-BPANeuGc inhibit BCR signal transduction. 3'-BPANeuGc is applicable to antigen-specific tolerance research.

Tyrphostin AG 568 is a tyrphostin tyrosine kinase inhibitor that induces erythroid differentiation. Tyrphostin AG 568 can be utilized in research related to autologous bone marrow transplantation.

BCR-ABL-IN-2 is an inhibitor of BCR-ABL1 tyrosine kinase, with IC₅₀s of 57 nM, 773 nm for ABL1^native and ABL1^T315I, respectively.

BCR-ABL-IN-5 (compound II) is a Bcr-Abl kinase (Breakpoint cluster region-Abelson) inhibitor. BCR-ABL-IN-5 inhibits Bcr-Abl^WT and Bcr-Abl^T3151 with the IC₅₀ value of 0.014 μM and 0.45 μM, respectively. BCR-ABL-IN-5 has some anti-proliferative activity against leukemic cells.

SNIPER(ABL)-047, conjugating HG-7-85-01 (ABL inhibitor) to MV-1 (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC₅₀ of 2 μM.

HSN748 is a Ponatinib (HY-12047) analogue and a multikinase inhibitor. HSN748 has inhibitory activity on FLT3, ABL1, RET, PDGFRα/β, MNK1, MNK2 and other kinases. HSN748 can inhibit the growth of chronic myeloid leukemia and acute myeloid leukemia cell lines and can be used in the study of leukemia.

BCR-ABL-IN-10 (compound B4) is a covalent and aryl vinyl sulfate (AVS)-containing BCR-ABL inhibitor with an IC₅₀ of 43.1 nM for ABL kinase. BCR-ABL-IN-10 forms a covalent and stable adduct with ABL kinase, leading to sustained inhibition of endogenous BCR-ABL activities. BCR-ABL-IN-10 can be used for the study of chronic myeloid leukemia (CML).

PDD-87 is an orally active, blood-brain barrier permeable kinase inhibitor, with IC₅₀ values ranging from 0.07 nM to 0.72 nM against ABL, SRC family, BTK kinases and their key mutants. PDD-87 induces antiproliferative effects in leukemia and lymphoma cells, and inhibits tumor growth in mouse xenograft models. PDD-87 can be used for the research of leukemia and lymphoma.

Debio 0617B, a multi-kinase inhibitor, reduces maintenance and self-renewal of primary human AML CD34⁺ stem/progenitor cells. Debio 0617B has a unique profile targeting key kinases upstream of STAT3/STAT5 signaling such as JAK, SRC, ABL, and class III/V receptor tyrosine kinases (TKs). Debio 0617B has documented efficacy in STAT3-driven solid tumors.

ML786 dihydrochloride is a potent and orally bioavailable Raf inhibitor, with IC₅₀s of 2.1, 4.2, and 2.5 nM for ^V600EΔB-Raf, wt B-Raf, and C-Raf, respectively. ML786 dihydrochloride also inhibits Abl-1, DDR2, EPHA2, KDR, and RET (IC₅₀=<0.5, 7.0, 11, 6.2, 0.8 nM). ML786 dihydrochloride can be used for the research of cancers.

PHA-680626 is an effective inhibitor of the interaction between Aurora-A and N-Myc. PHA-680626 inhibits kinase activity of AURKA and Bcr-Abl, and induces N-Myc degradation. PHA-680626 decreases phosphorylation of CrkL and histone H3. PHA-680626 shows anti-proliferative and pro-apoptotic activity on Imatinib (HY-15463)-resistant chronic myeloid leukemia cell lines and primary CD34+ cells.