MGCD-265-analog (structurally related to MGCD-265) is an orally bioavailable multitargeted tyrosine kinase inhibitor with potential antineoplastic activity with IC50 of 29 nM and 10 nM for c-Met and VEGFR2, respectively.IC50 value:10 nM (VEGFR2), 29 nM(c-Met) [1]Target:VEGFR, c-Metin vivo: MGCD-265-analog has a reasonable half-life, 1.2 h in rats and 5.8 h in dogs, and has an acceptable clearance, 0.33 L/(kg h) in rats and 1.1 L/(kg h) in dogs. The steady state volume of distribution was low in rats (0.25 L/kg) and reasonable in dogs (1.5 L/kg), while the oral bio-availability was determined to be 12% and 42% in rats and dogs, respectively. GCD-265-analog performed well in vivo against a panel of different human tumor types, particularly those that are driven by or overexpress c-Met (MNNGHOS and MKN45). Tumor growth inhibition at a dose of 20 mg/kg po once daily ranged from 41% to 94%. MGCD-265-analog was found to show spill-over inhibition of a number of kinases in addition to the intended c-Met/VEGFR2 activity. MGCD-265-analog has significant antitumor activity in vivo.[1]
Mersalyl (Salirgan) is a potent vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) inducer. Mersalyl induces VEGF and ENO1 mRNA expression. Mersalyl shows diuresis effects[1][2][3].
ALK-IN-22 (compound I-24) is a potent ALK inhibitor with IC50 values of 2.3, 3.7 and 2.9 nM for ALK, ALKL1196M and ALKG1202R, respectively. ALK-IN-22 down-regulated the phosphorylation of ALK and its downstream proteins. ALK-IN-22 induces apoptosis. ALK-IN-22 can be used for tumor research[1].
TX2-121-1 is a bivalent hydrophobically tagged adamantane derivative of TX1-85-1, a potent, selective, ATP-competitive Her3 (ErbB3) inhibitor; induces degradation and interferences with Her2/Her3 and c-Met/Her3 interactions, prevents Her3 heterodimerization, induces preferential death of Her3-dependent cell lines with an EC50 in the range of 0.8-1.4 uM.
Lorlatinib-d3 is the deuterium labeled Lorlatinib. Lorlatinib (PF-06463922) is a selective, orally active, brain-penetrant and ATP-competitive ROS1/ALK inhibitor. Lorlatinib has Kis of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALKL1196M
Syk Inhibitor II is a potent, high selective and ATP-competitive Syk inhibitor with an IC50 of 41 nM. Syk Inhibitor II inhibits 5-HT release from RBL-cells with an IC50 of 460 nM. Syk Inhibitor II shows less potent against other kinases and has anti-allergic effect[1].
PDGFRα/FLT3-ITD-IN-2 (Compound 13d) is a potent inhibitor of PDGFRα/FLT3 with IC50s of more than 20 and 1.654 μM, respectively. PDGFRα/FLT3-ITD-IN-2 has the potential for the research of acute myeloid leukemia or chronic eosinophilic leukemia[1].
Trk-IN-4 is a potent pan-Trk inhibitor in cell-based assays with IC50s of 1.9 nM, 2.6 nM and 1.1 nM for TrkA, TrkB and TrkC, respectively[1]. Anti-hyperalgesic effect[1].
ODM-203 is a potent FGFR and VEGFR families inhibitor with IC50s of 11, 16, 6, 35 nM towards recombinant FGFR1, FGFR2, FGFR3 and FGFR4 as well as 26, 9, 5 nM towards VEGFR1, VEGFR2 and VEGFR3, respectively. ODM-203 exhibits strong anti-tumor activity and induces anti-tumor immunity[1].
Lapatinib-d7 (GW572016-d7) ditosylate is the deuterium labeled Lapatinib. Lapatinib (GW572016) is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively[1][2].
c-Fms-IN-12 (Compound 4g) is an FMS kinase inhibitor. c-Fms-IN-12 can also inhibits c-KIT. c-Fms-IN-12 is a potential broad-spectrum anticancer agent against multiple cancer types. c-Fms-IN-12 induces A549 cell apoptosis[1].
Apatinib free base (YN968D1 free base) is an orally bioavailable tyrosine kinase inhibitor, which selectively targets VEGFR-2 (IC50=1 nM). Apatinib free base (YN968D1 free base) is an anti-angiogenic drug for the treatment of advanced or metastatic gastric cancer. Apatinib free base (YN968D1 free base) potently inhibits Ret, c-Kit and c-Src with IC50s of 13, 429 and 530 nM, respectively. It also inhibits cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ[1][2][3].
BT424 is a specific HCK inhibitor. BT424 can regulate macrophage activation and autophagy in vitro. BT424 ameliorates inflammation and kidney fibrosis in UUO model[1].
Lactacystin, an antibiotic Streptomyces spp. metabolite, is a potent and selective proteasome inhibitor with an IC50 of 4.8 μM for 20S proteasome. Lactacystin also inhibits the lysosomal enzyme cathepsin A[1]. Lactacystin inhibits cell growth and induces neurite outgrowth[2].
FGFR-IN-2 (compound 1) is a potent FGFR inhibitor with IC50s of 7.3 nM, 4.3 nM, 7.6 nM, 11 nM for FGFR1, FGFR2, FGFR3 and FGFR4, respectively. FGFR-IN-2 has the potential for cancer research[1].
Vulinacimab (HLX-06) is an anti-VEGFR-2 monoclonal antibody (mAb). Vulinacimab can be used in the research of cancers. VEGFR-2, overexpressed in certain tumors, is critical in angiogenesis and the proliferation, survival, migration and differentiation of endothelial cells[1].
AZD-3463 is an ALK/IGF1R inhibitor which overcomes multiple mechanisms of acquired resistance to crizotinib.IC50 Value:Target: ALK/IGF1R
EAI001 is a potent, selective mutant epidermal growth factor receptor (EGFR) allosteric inhibitor with an IC50 value of 24 nM for EGFRL858R/T790M. EAI001 can be used for research of cancer[1][2].
GIP (3-42), human acts as a glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist, moderating the insulin secreting and metabolic actions of GIP in vivo[1].
GGTI 2417 is the methyl ester prodrug of GGTI-2418, a highly potent, competitive, and selective inhibitor of GGTase I; exhibits potent inhibitory activity against Rap1 geranylgeranylation with IC50 of 400 nM; increases p27 protein levels and induces accumulation in the G0/G1 phase as well as apoptotic cell death in breast cancer cells, and prevents the degradation of nuclear p27.
c-Fms-IN-10 is the derivative of thieno [3,2-d] pyrimidine, an kinase inhibitor of FMS (Colony stimulating factor-1 receptor, CSF-1R) with IC50 of 2 nM.c-Fms-IN-10 has anti-tumor activity[1].
cFMS Receptor Inhibitor IV (Compound 42) is a potent cFMS inhibitor with an IC50 of 0.017 μM[1].
HTH-01-091 is a potent and selective, cell-permeable, ATP-competitive MELK inhibitor with biochemical IC50 of 10.5 nM; displays no significant activity for PIK3CA, mTOR, GSK3A and CDK7 (IC50>600 nM); exhibits substantially improved kinome selectivity in comparison with OTSSP167; induces MELK degradation, but demonstrates poor antiproliferative effects in basal-like breast cancer cell lines.
DB07107 is a potent drug resistant T315I mutant Bcr-Abl tyrosine kinase inhibitor. DB07107 is also a potent Akt1 inhibitor with an IC50 value of 360 nM[1][2].
Tivantinib is a novel and highly selective c-Met tyrosine kinase inhibitor with Ki of 355 nM.
IRAK4-IN-14 (compound 28) is a potent, selective and orally active IRAK4 inhibitor with an IC50 of 0.003 µM. IRAK4-IN-14 shows good PK parameters in rats and mouse. IRAK4-IN-14 shows synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with Acalabrutinib[1].
Utatrectinib (AZD-7451) is a potent, selective and orally active Trk inhibitor. Utatrectinib blocks TrkC activation and associated tumorigenic behaviors[1].
Antiproliferative agent-34 (Compound A14) is a multi-target kinase inhibitor, with an IC50 of 177 nM and 1567 nM for EGFR L858R/T790M and EGFR WT. Antiproliferative agent-34 also inhibits JAK2, ROS1, FLT3, FLT4, PDGFRα with IC50 of 30.93, 106.90, 108.00, 226.60, 42.53 nM. Antiproliferative agent-34 inhibits H1975 and HCC827 cells proliferation with IC50 values below 40 nM under normoxic condition, and the anti-proliferation potency achieves 4–6-fold improvement (IC50 values < 10 nM) under hypoxic condition[1].
Pazopanib Hydrochloride is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with an IC50 of 10, 30, 47, 84, 74, 140 and 146 nM, respectively.
Woodtide is a substrate for the DYRK (DYRK) family of kinases whose sequence is based on that around the DYRK phosphorylation site in FKHR[1][2].