bcr

GMB-475, also known as PROTAC BCR-ABL1 ligand 1, allosterically targets and binds to the BCR-ABL1 protein. It effectively recruits the E3 ligase Von Hippel-Lindau, leading to the ubiquitination and subsequent degradation of BCR-ABL1 [1].

BCR-ABL-IN-4 is a BCR-ABL inhibitor exhibiting anticancer activity with an inhibitory effect on cancer cell growth, specifically on K562 cells (IC50: 0.67 nM) and BCR-ABL T315I-transfected Ba F3 cells (IC50: 16 nM).

PROTAC BCR-ABL Degrader-1 (compound PROTAC 1), featuring a 2-oxoethyl linker, induces Bcr-Abl degradation via the ubiquitin-proteasome pathway and exhibits antiproliferative effects on K562 cells, indicating its potential in cancer research [1].

BCR-ABL-IN-6 (9h) is an imatinib derivative and a selective inhibitor of Bcr-Abl kinase, showing activity on Bcr-AblWT (IC50: 4.6 nM) and Bcr-AblT3151 (IC50: 277 nM). BCR-ABL-IN-6 (9h) is utilized in studying chronic myeloid leukemia treatment.

BCR-ABL-IN-8 (compound 26f) is a BCR-ABL inhibitor characterized by a trimethoxy group [1].

BCR-ABL1-IN-1 is a highly potent, orally bioavailable inhibitor with remarkable specificity towards ABL kinase, showing significant promise for elucidating the precise role of ABL kinases in the central nervous system, particularly in preclinical investigations [1].

PROTAC BCR-ABL1 ligand 1 is the ligand of PROTAC .

BCR-ABL-IN-5 is a Bcr-Abl (Breakpoint cluster region-Abelson) kinase inhibitor that acts on Bcr-AblWT (IC50: 0.014 μM) and Bcr-AblT3151 (IC50: 0.45 μM) and exhibits some anti-proliferative effects on leukemic cells. effect.

BCR-ABL-IN-7 is a WT and T315I mutant ABL kinase inhibitor.BCR-ABL-IN-7 potently inhibits WT and T315I mutant ABL kinase activity.BCR-ABL-IN-7 can be used in chronic myelogenous leukemia (CML) research.

BCR-ABL kinase-IN-3 (example 1), a potent BCR-ABL inhibitor, is significant in the study of acute myeloid leukemia (AML) [1].

BCR-ABL-IN-3 is a highly effective, irreversible inhibitor of Bcr-Abl, with an IC50 value of ≤100 nM for Ba F3 Bcr-Abl T3151, displaying significant anti-cancer activity.

BCR-ABL-IN-2 is a BCR-ABL1 tyrosine kinase inhibitor (IC50s: 57 nM, 773 nM for ABL1 native and ABL1 T315I).

BCR-ABL-IN-1 is a BCR-ABL tyrosine kinase inhibitor (pIC50: 6.46) and may be used in the research of chronic myelogenous leukemia.

LXH254 is a potent C-Raf and B-Raf inhibitor.

Bosutinib (SKI-606) is a synthetic quinolone derivative and dual kinase inhibitor that targets both Abl (IC50: 1 nM) and Src (IC50: 1.2 nM) kinases.

Imatinib Mesylate (STI-571) is a tyrosine kinase receptor inhibitor with antineoplastic activity (IC50s: 0.6 μM, 0.1 μM and 0.1 μM for v-Abl, c-Kit and PDGFR, respectively).

Dasatinib monohydrate (BMS-354825 Monohydrate) is an orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib monohydrate binds to and inhibits the growth-promoting activities of these kinases. Apparently, because of its less stringent binding affinity for the BCR-ABL kinase, Dasatinib monohydrate has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations.

Ponatinib (AP24534) is an orally available, multitargeted kinase inhibitor with IC50 values of 0.37 nM (Abl), 1.1 nM (PDGFRα), 1.5 nM (VEGFR2), 2.2 nM (FGFR1), and 5.4 nM (Src).

1. trans-Cinnamaldehyde (Phenylacrolein) exhibits excellent anti-inflammatory activities and antidepressant-like effects in stressed mid-aged rats as a COX-2 inhibitor. 2. Cinnamic aldehyde induces apoptosis of CML cells in vitro, down-regulation of the expression and function of BCR-ABL may be one of its most important anti-leukemia mechanisms. 3. Cinnamic aldehyde and cinnamic acid are cardioprotective in a rat model of ischemic myocardial injury, the mechanism is related to anti-oxidative and anti-inflammatory properties.

Dasatinib (BMS-354825) is an orally active, ATP-competitive tyrosine kinase inhibitor that targets Src and Bcr-Abl (Ki=16 30 pM), with antitumor activity, used in the treatment of leukemia and lymphoma.

Imatinib (STI571) is a multi-targeted receptor tyrosine kinase inhibitor that selectively inhibits the kinase activities of BCR ABL, v-Abl, PDGFR, and c-kit with oral activity. Imatinib has antitumor activity for the treatment of chronic granulocytic leukemia.

Nilotinib (AMN107) is a Bcr-Abl tyrosine kinase inhibitor with oral activity. Nilotinib has antitumor activity and may be used for the treatment of Imatinib-resistant chronic myelogenous leukemia (CML).

Nilotinib monohydrochloride monohydrate (Nilotinib (monohydrochloride monohydrate)) is significantly potent BCR-ABL against, is a second generation tyrosine kinase inhibitor (TKI), and is active against many BCR-ABL mutants.

AN-019 (NRC-019) is a Bcr-Abl kinase inhibitor with antitumor activity for the study of chronic myelogenous leukemia (CML) and breast cancer.

(S,R,S)-AHPC TFA (VHL ligand 1 TFA) (VH032-NH2 TFA) is a VH032-based ligand designed for von Hippel-Lindau (VHL) protein recruitment. This compound can be linked to protein ligands (e.g., BCR-ABL1) using a linker to create PROTACs (e.g., GMB-475), which effectively induce the degradation of BCR-ABL1, demonstrated by an IC50 of 1.11 μM in Ba/F3 cells.

PF-06651481-00 (Bosutinib Isomer I) is a Bosutinib analog and a Bcr-Abl inhibitor.

PPY A is a potent inhibitor of T315l mutant and wild-type Abl kinase (IC50 of 9 and 20 nM, respectively).PPY A also inhibits the growth of Bcr-Abl T315l mutant or wild-type Bcr-Abl genetically transformed cells.

Vamotinib (PF-114) is an orally active and specific tyrosine kinase inhibitor with antiproliferative and antitumour activity.Vamotinib inhibits the phosphorylation of BCR/ABL and BCR/ABL-T315I, which promotes apoptosis. Vamotinib is used to study drug-resistant Philadelphia chromosome-positive (Ph+) leukaemia and Alzheimer's disease.

P-gp BCRP-IN-1 (compound 19) is a relatively safe, orally active, and efficient inhibitor of the efflux transporters P-gp and BCRP, which reverses resistance and enhances the oral bioavailability of Paclitaxel (PTX) [1].

P-gp BCRP-IN-2 (compound 15), an oxadiazole derivative, functions as a dual inhibitor targeting both the ABC transporter P-glycoprotein (IC50: 1.6 nM) and BCRP (IC50: 600 nM). Additionally, it bolsters the anti-proliferative impact of Doxorubicin in the drug-resistant HT29 DX and MDCK-MDR1 human adenocarcinoma colon cancer cell lines [1].

33-BCRP inhibitor is a compound that blocks the action of breast cancer resistance protein (BCRP), enhancing the susceptibility of mitoxantrone-resistant H460/MX20 lung cancer cells to the cytotoxic effects of mitoxantrone, both individually and when combined with UV radiation. Additionally, it enhances the sensitivity of KB-C2 epidermal carcinoma cells, which overexpress P-glycoprotein (P-gp) or multidrug resistance protein (MDR), to colchicine-induced apoptosis. Furthermore, at a concentration of 5 µM, it boosts the intracellular accumulation of mitoxantrone in H460/MX20 cells.

BGG463 (K 0859) can inhibit c-ABL-T334I, BCR-ABL and BCR-ABL-T315I variants with a 50% inhibitory concentration (IC50) of 0.25 μM, 0.09 μM and 0.590 μM, respectively.

AST 487 (NVP-AST 487) is a RET kinase inhibitor, inhibiting RET autophosphorylation and activation of downstream effectors. It also can inhibit Flt-3.

Degrasyn (WP1130) (WP1130), a specific deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor, also inhibits Bcr Abl, which is a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT).

AT9283 (J-504568) is an effective multi-targeted inhibitor of JAK2(IC50=1.2 nM) and JAK3(IC50=1.1 nM), Aurora A, Aurora B and Abl(T315I).

Bafetinib (INNO-406) (INNO-406) is an effective and specific dual Bcr-Abl Lyn inhibitor (IC50: 5.8 19 nM), and no inhibition of the phosphorylation of the T315I mutant and less effective to c-Kit and PDGFR.

DCC-2036 (Rebastinib (DCC-2036)) is a conformational control Bcr-Abl inhibitor for Abl1(WT, IC50: 0.8 nM) and Abl1(T315I, IC50: 4 nM), also inhibits LYN, SRC, HCK, FGR, FLT3, KDR, and Tie-2, and low activity to c-Kit. Rebastinib aimed at the Angiopoietin2-Tie2 pathway.

Asciminib (ABL001) (ABL001) is a potent and selective Bcr-Abl inhibitor (Kd: 0.5–0.8nM).

Olverembatinib (GZD 824) is an orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT, IC50: 0.34 nM) and Bcr-Abl(T315I, IC50: 0.68 nM).

Nocodazole (Oncodazole) is a reversible inhibitor of microtubule polymerization and an inhibitor of Bcr-Abl. Nocodazole has antitumor activity, blocks the cell cycle and induces apoptosis.

Carboxyamidotriazole Orotate (L-651582 Orotate) is a cytostatic inhibitor of non-voltage-operated calcium channels and associated signaling pathways. As the orotate salt form of Carboxyamidotriazole (CAI), it is an orally bioavailable signal transduction inhibitor with in vitro antileukaemic activity, exhibiting anti-tumor, anti-inflammatory, and antiangiogenic effects.

Orelabrutinib (ICP-022) is an orally active and irreversible inhibitor of Bruton's tyrosine kinase (BTK).

PD173955 is src family-selective tyrosine kinase inhibitor with IC50 of ~22 nM for Src, Yes and Abl kinase; less potent for FGFRα and no activity on InsR and PKC.

PCI 29732 is a selective and irreversible Btk inhibitor with IC50 of 8.2 nM in a FRET based biochemical enzymology assay.

Multi-kinase inhibitor 1 (Multi-kinase inhibitor I) is a Multi-kinase inhibitor.

CNX-774 is a highly specific, irreversible, and orally active BTK inhibitor (IC50<1 nM).

Rigosertib sodium (ON-01910), a non-ATP-competitive inhibitor of PLK1(IC50=9 nM), exhibits 30-fold higher specificity activity over Plk2 and no effect on Plk3.

Acalabrutinib (ACP-196), also known as ACP-196, is an orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

Radotinib (IY-5511), and sometimes referred to by its investigational name IY5511, is a drug for the treatment of different types of Y, most notably Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) with resistance or intolerance of other tyrosine kinase Bcr-Abl inhibitors

GNF-2 is a highly selective non-ATP competitive inhibitor of Bcr-Abl.

1. Cinnamaldehyde (Cinnamic Aldehyde) has antipyretic activity. 2. Cinnamaldehyde is a sedative agent. 3. Cinnamaldehyde inhibits invasive capabilities of MDA-MB-435S cells was correlated with down-regulating the expression of miR-27a. 4. Cinnamaldehyde induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects. 5. Cinnamaldehyde appears to be a promising candidate as an adjuvant in combination therapy with 5-fluorouracil (5-FU) and oxaliplatin (OXA), two chemotherapeutic agents used in CRC treatment. The possible mechanisms of its action may involve the regulation of drugmetabolizing genes. 6. Cinnamaldehyde plays a certain role in inhibiting the occurrence and progression of melanoma and its action mechanism may be manifested by inhibiting expression of VEGF and HIF-α, thus blood vessel simulation and formation of new blood vessels of melanoma cells, and growth of tumors accordingly.