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[1].
BCR-ABL-IN-2 is an inhibitor of BCR-ABL1 tyrosine kinase, with IC50s of 57 nM, 773 nm for ABL1native and ABL1T315I, respectively.
BCR-ABL-IN-5 (compound II) is a Bcr-Abl kinase (Breakpoint cluster region-Abelson) inhibitor. BCR-ABL-IN-5 inhibits Bcr-AblWT and Bcr-AblT3151 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[1].
Antiproliferative agent-30 (Compound 8g) inhibits tubulin assembly and inhibits FLT3 and Abl1. Antiproliferative agent-30 has vascular-disrupting activity. Antiproliferative agent-30 has broad antiproliferative activities against cancer cell lines (IC50s: 0.054 nM, 0.008 nM, 0.144 nM for HCT-116, K562, MV-4-11 cells respectively). Antiproliferative agent-30 also has anticancer effect against AML with FLT3-ITD-TKD mutation[1].
Rebastinib (DCC-2036) is a conformational control Bcr-Abl inhibitor for Abl1WT and Abl1T315I with IC50 of 0.8 nM and 4 nM, also inhibits SRC, KDR, FLT3, and Tie-2, and low activity to seen towards c-Kit.
Ponatinib (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[1].
ON 146040 is a potent PI3Kα and PI3Kδ (IC50≈14 and 20 nM, respectively) inhibitor. ON 146040 also inhibits Abl1 (IC50<150 nM).
Nilotinib is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity.
AP 24149 is a potent Src-Abl dual inhibitor with IC50 values of 9.1, 3.6 nM for Src and Abl, respectively[1].
PD180970 is a highly potent and ATP-competitive p210Bcr-Abl kinase inhibitor, with an IC50 of 5 nM for inhibiting the autophosphorylation of p210Bcr-Abl. PD180970 also inhibits Src and KIT kinase with IC50s of 0.8 nM and 50 nM, respectively. PD180970 indcues apoptosis of K562 leukemic cells, and can be used for chronic myelogenous leukemia research[1][2][3].
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[1].
Radotinib(IY-5511) is a novel and selective BCR-ABL1 tyrosine kinase inhibitor with IC50 of 34 nM for wild-type BCR-ABL1 kinase.IC50 value: 34 nM [1]Target: BCR-ABL1 inhibitorRadotinib is a BCR-ABL1 specific 2nd-generation tyrosine kinase inhibitor. According to recently conducted in vitro kinase assays, the IC50 value for radotinib against wild-type BCR-ABL1 kinase was 34 nM, which is relatively lower compared with the IC50 levels of c-kit (1,324 nM), PDGFR (PDGFRα, 75.5 nM; PDGFRβ, 130 nM) and src (>2,000 nM). Also, radotinib effectively inhibited the proliferation of common mutant clones of BCR-ABL1, with the exception of T315I. In an off-target kinase assay to assess safety, DDR, EPHB, LYN, and PDGFR kinases were inhibited below the 180 nM level.
Asciminib (ABL001) is a potent and selective allosteric Bcr-Abl inhibitor; inhibits Ba/F3 cells grown with an IC50 of 0.25 nM.
XL228 is a multi-targeted tyrosine kinase inhibitor with IC50s of 5, 3.1, 1.6, 6.1, 2 nM for Bcr-Abl, Aurora A, IGF-1R, Src and Lyn, respectively.
AT9283 lactic acid is a multi-targeted kinase inhibitor with potent activity against Aurora A/B, JAK2/3, Abl (T315I) and Flt3 (IC50s ranging from 1 to 30 nM). AT9283 lactic acid inhibits growth and survival of multiple solid tumors in vitro and in vivo[1][2].
Bosutinib is an oral Src/Abl tyrosine kinase inhibito with IC50 of 1.2 nM and 1 nM, respectively[1].
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.
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].
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.
CZC-8004 is a pan-kinase inhibitor and binds a range of tyrosine kinases, including ABL kinase.
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].
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.
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.
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].