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.IC50 value: 22 nMTarget: Src kinase inhibitorin vitro: PD173955 inhibits the growth of MDA-MB-468 and MCF-7 breast cancer cells with IC50s of 500 nM and 1 μM, respectively, with an accumulation of suspended cells. Cells treated with PD173955 show a near complete redistribution to the G2-M phase of the cell cycle in comparison with control cells, and quantitation of mitotic indices by immunofluorescence microscopy shows an accompanying accumulation of mitotic cells.PD173955 shows antimitotic activity in breast cancer cells with high or low src and yes kinase activities, the antimitotic activity of PD173955 is independent of cell type or malignant transformation [1]. PD173955 inhibits both the active and inactive forms of Abl. By contrast, Imatinib only inhibits the active form of the enzyme. In addition, the Ki for inhibition of Abl by PD173955 is very low, making it a more potent inhibitor of Abl and a more effective inhibitor of cancer cell proliferation than Imatinib [2]. PD173955, a Src family-specific tyrosine kinase inhibitor, increases the susceptibility of HT29 cells to anoikis in a dose- and time-dependent manner [3].
Dasatinib hydrochloride is a potent and dual AblWT/Src inhibitor IC50 of 0.6 nM/0.8 nM respectively; also inhibits c-KitWT/c-KitD816V with IC50 of 79 nM/37 nM.
AG957 (Tyrphostin AG957;NSC 654705) is a tyrosine kinase inhibitor with anti-BCR/ABL tyrosine kinase activity[1][2]. AG957 is a bcr/abl kinase inhibitor with an IC50 of 2.9 μM for p210bcr/abl autokinase activity[3].
Cenisertib (AS-703569) is a 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)[1]. Cenisertib inhibits tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia[2].
SNIPER(ABL)-033, conjugating HG-7-85-01 (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 0.3 μM[1].
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 Ki of 8.1 nM. PD173952 induces apoptosis[1][2].
Multi-kinase inhibitor 1 is a potent multi-kinase inhibitor. Multi-kinase inhibitor 1 has the potential for diseases or disorders associated with abnormal or deregulated tyrosine kinase activity, particularly diseases associated with the activity of PDGF-R, c-Kit and Bcr-abl[1].
KW-2449 is a multi-targeted kinase inhibitor of FLT3, ABL, ABLT315I and Aurora kinase with IC50s of 6.6, 14, 4 and 48 nM, respectively.
Bafetinib is a Lyn and Bcr-Abl tyrosine kinase inhibitor with potential antineoplastic activity.
BCR-ABL-IN-1 is an inhibitor of BCR-ABL tyrosine kinase, with a pIC50 of 6.46, and may be used in the research of chronic myelogenous leukemia.
CHMFL-ABL-121 is a highly potent type II ABL kinase inhibitor with IC50s of 2 nM and 0.2 nM against purified inactive ABL wt and T315I kinase protein, respectively[1].
Ruserontinib (SKLB1028) is an orally active multikinase inhibitor of EGFR, FLT3 and Abl, with an IC50 value of 55 nM for human FLT3, and has antitumor activity[1].
Imatinib is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
CZC-8004 is a pan-kinase inhibitor and binds a range of tyrosine kinases, including ABL kinase.
Imatinib Mesylate is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
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.
Imatinib D8 (STI571 D8) is a deuterium labeled Imatinib (STI571). Imatinib is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, v-Abl, PDGFR and c-kit kinase activity[1][2].
SNIPER(ABL)-024, conjugating GNF5 (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 5μM[1].
Flumatinib mesylate (HH-GV-678 mesylate), a derivative of imatinib, is a multi-kinase inhibitor with IC50 Values of 1.2 nM, 307.6 nM and 2662 nM for c-Abl, PDGFRβ and c-Kit respectively.IC50 Value: 1.2 nM (c-Abl); 307.6 nM(PDGFRβ); 2662 nM (c-Kit) [1]Target: c-Abl; c-Kit; PDGRFβin vitro: HH-GV-678 can predominantly inhibit the autophosphorylation of Bcr-Abl in K562 cell. In higher concentration, HH-GV-678 can inhibit the phosphorylation of c-Kit in Mo7e cell and the phosphorylation of PDGFR in Swiss3T3 cell, however, HH-GV-678 has no or little effect on other tyrosine kinase including EGFR/KDR/c-Src andHER2 [1]. Flumatinib effectively overcame the drug resistance of certain KIT mutants with activation loop mutations (i.e., D820G, N822K, Y823D, and A829P) [2].in vivo: The purpose of this study was to identify the metabolites of flumatinib in CML patients, with the aim of determining the main metabolic pathways offlumatinib in humans after oral administration. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry revealed 34 metabolites; 7 primary metabolites were confirmed by comparison with synthetic reference standards. The results show that the parent drugflumatinib was the main form recovered in human plasma, urine, and feces. The main metabolites of flumatinib in humans were the products of N-demethylation, N-oxidation, hydroxylation, and amide hydrolysis [3].
Lyn-IN-1 is a potent and selective dual Bcr-Abl/Lyn inhibitor, extracted from patent WO2014169128A1.
Nilotinib monohydrochloride monohydrate is a second generation tyrosine kinase inhibitor (TKI), is significantly more potent against BCR-ABL than Imatinib, and is active against many Imatinib-resistant BCR-ABL mutants.
Ponatinib is a potent, orally available 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.
GNF-7 inhibits Bcr-Abl WT and Bcr-Abl T315I with IC50 of 133 nM and 61 nM, respectively. IC50 value: 133 nM (Bcr-Abl WT), 61 nM (Bcr-Abl T315I)Target: Bcr-Ablin vitro: GNF-7 is amongst the first type II inhibitors capable of inhibiting T315I to be described and will serve as a valuable lead to design next generation Bcr-Abl kinase inhibitors. GNF-7 exhibits some selectivity (4 to 100-fold) for T315I Bcr-Abl (IC50 = 11 nM, in Ba/F3 cell line) relative to kinases such as TPR-Met, NPM-ALK, JAK-3, Flt-3. in vivo: GNF-7 displays significant efficacy against T315I-Bcr-Abl without appreciable toxicity in a bioluminescent xenograft mouse model using a transformed T315I-Bcr-Abl-Ba/F3 cell line that has a stable luciferase expression. GNF-7 exhibits excellent pharmacokinetic parameters in mice, with good systemic exposure (AUC = 26656 hrs*nM, Cmax = 3.6 uM) along with reasonable half life (t1/2=3.2 hrs) and favorable oral bioavailability (BAV=36%) being observed following oral administration of a single dose of 20 mg/kg.
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[1].
Flumatinib is a multi-kinase inhibitor with IC50 Values of 1.2 nM, 307.6 nM and 2662 nM for c-Abl, PDGFRβ and c-Kit respectively.IC50 Value: 1.2 nM (c-Abl); 307.6 nM(PDGFRβ); 2662 nM (c-Kit) [1]Target: c-Abl; c-Kit; PDGRFβin vitro: HH-GV-678 can predominantly inhibit the autophosphorylation of Bcr-Abl in K562 cell. In higher concentration, HH-GV-678 can inhibit the phosphorylation of c-Kit in Mo7e cell and the phosphorylation of PDGFR in Swiss3T3 cell, however, HH-GV-678 has no or little effect on other tyrosine kinase including EGFR, KDR, c-Src and HER2 [1]. Flumatinib effectively overcame the drug resistance of certain KIT mutants with activation loop mutations (i.e., D820G, N822K, Y823D, and A829P) [2].in vivo: The purpose of this study was to identify the metabolites of flumatinib in CML patients, with the aim of determining the main metabolic pathways off lumatinib in humans after oral administration. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry revealed 34 metabolites; 7 primary metabolites were confirmed by comparison with synthetic reference standards. The results show that the parent drugflumatinib was the main form recovered in human plasma, urine, and feces. The main metabolites of flumatinib in humans were the products of N-demethylation, N-oxidation, hydroxylation, and amide hydrolysis [3].
Adaphostin (NSC 680410), the adamantyl ester of AG957, is a potent p210bcr/abl inhibitor (IC50=14 μM). Adaphostin induces apoptosis in T-lymphoblastic human leukemia cell lines (IC50 ranging from 17 to 216 nM). Adaphostin has significant and selective activity against chronic and acute myeloid leukemia cells. Adaphostin increased the level of reactive oxygen species (ROS) within CLL B cells[1][2][3].
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[1].
Nilotinib D6 (AMN107 D6) is a deuterium labeled Nilotinib. Nilotinib is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity[1].
BCR-ABL-IN-6 (9h) is a selective Bcr-Abl kinase inhibitor, with IC50s of 4.6 and 227 nM for Bcr-AblWTand A Bcr-AblT3151 respectively. BCR-ABL-IN-6 (9h) can inhibits Bcr-Abl kinase with strong affinity inside the cells, with an EC50 of 14.6 nM. BCR-ABL-IN-6 (9h) is an imatinib derivative which can be used for research of chronic myelogenous leukemia [1].
Nilotinib (AMN107) hydrochlorid is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity[1][2][3].