Bcr-Abl Inhibitor

CHMFL-ABL-039 is a type II native ABL kinase and drug-resistant V299L mutant BCR-ABL inhibitor with the IC₅₀s of 7.9 nM and 27.9 nM, respectively. CHMFL-ABL-039 is used in the research of chronic myeloid leukemia.

LS-104 (Tyrene CR-4) is a non-ATP-competitive kinase inhibitor against JAK2, Bcr-Abl and FLT3. LS-104 potently induces apoptosis in JAK2V617F-positive cells and inhibits JAK2 autophosphorylation and downstream signal transduction. LS-104 also inhibits proliferation and induces potent cytotoxic effects in FLT3 expressing leukemic cells. LS-104 is a hydroxystyryl-acrylonitrile compound, which is promising for research of myeloproliferative disorders and refractory/relapsed hematologic malignancies.

c-ABL-IN-4 is a potent inhibitor of c-Abl. Activation of c-Abl has been implicated in various diseases, notably cancer. c-ABL-IN-4 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 54).

BCR-ABL-IN-4 is a BCR-ABL inhibitor with anticancer effects. BCR-ABL-IN-4 inhibits the cancer cell growth with IC₅₀ values of 0.67 nM and 16 nM for K562 cells and BCR-ABL T315I transfected Ba/F3 cells, respectively (WO2021143927A1; compound 11).

BRAFV600E/ABL2-IN-1 is a BRAF^V600E (IC₅₀ = 0.088 μM)/ABL2 (IC₅₀ = 0.3 μM) dual inhibitor. BRAFV600E/ABL2-IN-1 can diminish P-glycoprotein expression. BRAFV600E/ABL2-IN-1 effectively inhibits p-CrkL (Abl2 signaling) and p-ERK1/2 (BRAF^V600E pathway) in A375-R melanoma cells. BRAFV600E/ABL2-IN-1 causes cell cycle arrest. BRAFV600E/ABL2-IN-1 significantly increases the percentage of late apoptotic cells. BRAFV600E/ABL2-IN-1 can be used for the study of melanoma.

GNF-6 (Compound 14) inhibits the gatekeeper threonine residue mutation of BCR-ABL-T315I with IC₅₀s of 0.25 μM, 0.09 μM and 0.590 μM for c-ABL-T334I, BCR-ABL and BCR-ABL-T315I variants, respectively. GNF-6, an ATP competitive inhibitor, disrupts the assembly of the hydrophobic spine (a network of hydrophobic interactions), thereby locking the kinase in an inactive ‘DFG-out’ conformation.

Nilotinib-13C,d3 is a deuterated labeled Nilotinib. Nilotinib is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity.

Dasatinib (monohydrate) (Standard) is the analytical standard of Dasatinib (monohydrate). This product is intended for research and analytical applications. Dasatinib (BMS-354825) monohydrate is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The Kis 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.

c-ABL-IN-6 (compound A6) is a c-ABL inhibitor with IC₅₀ value of 16.6 nM. c-ABL-IN-6 displays higher neuroprotective effects against SH-SY5Y cell death induced by MPP⁺ (HY-W008719). c-ABL-IN-6 can be used for the research of neurodegenerative disorder.

IHMT-TRK-284 (Compound 34) is a potent, orally active type II TRK kinase inhibitor with IC₅₀ values of 10.5, 0.7, and 2.6 nM to TRKA, B, and C respectively. IHMT-TRK-284 displays great selectivity profile in the kinome and good in vivo antitumor efficacies.

SNIPER(ABL)-039, conjugating Dasatinib (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC₅₀ of 10 nM. IC₅₀s are 0.54 nM, 10 nM, 12 nM, and 50 nM for ABL, cIAP1, cIAP2, XIAP, respectively.

PonatiLink-1-24 is an Abelson murine leukemia (ABL) enzyme inhibitor.

Radotinib (IY-5511) dihydrochloride is an orally active and BBB-permeable selective tyrosine kinase Bcr-Abl1 inhibitor with an IC₅₀ of 34 nM. Radotinib dihydrochloride has anti-prion and anti-tumor activities. Radotinib dihydrochloride can inhibit the proliferation, induce cell cycle arrest and apoptosis of tumor cells . Radotinib dihydrochloride can be used in the research of cancer such as chronic myeloid leukemia and multiple myeloma, as well as neurodegenerative diseases such as prion diseases.

Multi-kinase-IN-14 is an orally active and blood-brain barrier-permeable multi-kinase inhibitor. Multi-kinase-IN-14 reduces the excessive phosphorylation of α-synuclein by inhibiting four kinases (ABL1, DYRK1A, GSK3β, and LRRK2) and stabilizing microtubules. Multi-kinase-IN-14 is applicable for research on neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease.

AP-24226 is a potent inhibitor of Scr/ABL.

Tyrosine kinase-IN-9 (Compound B) is the inhibitor for c-Abl. Tyrosine kinase-IN-9 can be used in research of neurodegenerative diseases including Alzheimer’s and Parkinson’s disease.

BCR-ABL kinase-IN-3 (example 1) is a potent inhibitor of BCR-ABL that plays an important role in acute myeloid leukemia (AML) research.

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

CHMFL-48 is an orally active BCR-ABL kinase inhibitor targeting both wild-type (wt) and various imatinib-resistant mutants. The IC₅₀ values for CHMFL-48 against ABL wild-type and ABL T315I mutant are 1 nM and 0.8 nM, respectively. CHMFL-48 exerts its effects by blocking the autophosphorylation of BCR-ABL wild-type and mutant forms, which impacts downstream signaling mediators such as STAT5 and CRKL, leading to cell cycle arrest and induction of apoptosis. CHMFL-48 holds potential for research into chronic myeloid leukemia (CML).

Dasatinib (hydrochloride) (Standard) is the analytical standard of Dasatinib (hydrochloride). This product is intended for research and analytical applications. Dasatinib (BMS-354825) hydrochloride is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The Kis are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib hydrochloride inhibits Bcr-Abl and Src with IC50s of <1.0 nM and 0.5 nM, respectively. Dasatinib hydrochloride also induces apoptosis and autophagy.