NVP-BHG712 is a specific EphB4 inhibitor with ED50 of 25 nM that discriminates between VEGFR and EphB4 inhibition; also shows activity against c-Raf, c-Src and c-Abl with IC50 of 0.395 μM, 1.266 μM and 1.667 μM, respectively.IC50 value: 25 nM(EC50)Target: EphB4 receptor;c-Raf; c-Srcin vitro: NVP-BHG712 treatment also dose dependently leads to the inhibition of RTK autophosphorylation in stable transfected A375 melanoma cells with EC50 of 25 nM and 4.2 μM for EphB4 and VEGFR2, respectively [1].in vivo: In a growth factor-induced angiogenesis model, NVP-BHG712 (3 mg/kg, p.o) significantly suppresses VEGF stimulated tissue formation and vascularization by inhibiting EphB4 forward signaling. Furthermore, NVP-BHG712 (10 mg/kg/kg, p.o.) potently reverses VEGF enhanced tissue formation and vessel growth. NVP-BHG712 (3 mg/kg, p.o.) shows a long lasting exposure with concentrations around 10 μM in plasma as well as in lung and liver tissue for up to 8 hours, and thus results in a long lasting inhibition of EphB4 kinase activity in mice [1].
7,8-Dihydroxyflavone is a potent and selective TrkB agonist that mimics the physiological actions of Brain-derived neurotrophic factor (BDNF). Displays therapeutic efficacy toward various neurological diseases[1].
Telatinib (Bay 57-9352) is an orally active, small molecule inhibitor of VEGFR2, VEGFR3, PDGFα, and c-Kit with IC50s of 6, 4, 15 and 1 nM, respectively.
UNC2025 is a potent and orally bioavailable Mer/Flt3 dual inhibitor with IC50 of 0.8/0.74 nM for Mer/Flt3.IC50 value: 0.8/0.74 nM(MER/FLT3)Target: Mer/Flt3 inhibitorUNC2025 was capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome pro ling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined.
PHI-101 is an orally active FLT3 inhibitor that overcomes resistance to multiple drug-resistant mutations. PHI-101 potently inhibits FLT3 single activating mutations (ITD or TKD mutants) and has inhibitory activity against FLT3 double (ITD/D835Y or ITD/F691L) and triple (ITD/D835Y/F691L) resistance mutations. PHI-101 has potential for research in relapsed or refractory acute myeloid leukemia (AML)[1].
SU4312 is the racemate of (Z)-SU4312 and (E)-SU4312. (Z)-SU4312 inhibits PDGFR and FLK-1 with IC50s of 19.4 and 0.8 μM, respectively. (E)-SU4312 inhibits PDGFR, FLK-1, EGFR, HER-2, and IGF-1R with IC50s of 24.2, 5.2, 18.5, 16.9 and 10.0 μM, respectively[1].
N-(p-Coumaroyl) Serotonin is a polyphenol isolated from the seeds of safflower and has antioxidative, anti-atherogenic and anti-inflammatory properties. N-(p-Coumaroyl) Serotonin inhibits PDGF-induced on phosphorylation of PDGF receptor and Ca2+ release from sarcoplasmic reticulum[1]. N-(p-Coumaroyl) Serotonin ameliorates atherosclerosis and distensibility of the aortic wall in vivo and is usually used for the atherosclerosis research[2].
Sp-5,6-DCl-cBIMPS is a potent and specific cAMP-dependent protein kinases (cAMP-PK) activator. Sp-5,6-DCl-cBIMPS stimulates insulin release. Sp-5,6-DCl-cBIMPS inhibits U46619-induced activation of Rho, Gq and G12/G13 in platelets[1][2][3].
Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive ALK and c-Met inhibitor with IC50s of 20 and 8 nM, respectively. Crizotinib inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC50s of 24 and 11 nM in cell-based assays, respectively. Crizotinib is also a ROS1 inhibitor. Crizotinib has effective tumor growth inhibition[1][2][3].
Sotiburafusp alfa is a bispecific fusion protein, which is a humanized VEGFR-1 extracellular domain fragment (129-228, 1-100 in the current sequence) fused via the peptide linker 101GGSGGSGGSGGSGGS115 to the N-terminus of the heavy chain (116-564) of a humanized IgG1-kappa anti-human PD-L1 heavy chain variant L352>A, L353>A. Sotiburafusp alfa is also an angiogenesis inhibitor[1].
Nitidine chloride, a potential anti-malarial lead compound derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through diverse pathways, including inducing apoptosis, inhibiting STAT3 signaling cascade, DNA topoisomerase 1 and 2A, ERK and c-Src/FAK associated signaling pathway. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kB pathway[1][2][3][4][5][6].
JH-XIV-68-3 is a selective macrocyclic inhibitor of DYRK1A/B. JH-XIV-68-3 displays selectivity for DYRK1A and close family member DYRK1B in biochemical and cellular assays. JH-XIV-68-3 demonstrates antitumor efficacy in head and neck squamous cell carcinoma (HNSCC) cell lines[1].
Mavelertinib is a selective, orally available and irreversible EGFR tyrosine kinase inhibitor (EGFR TKI), with IC50s of 5, 4, 12 and 3 nM for Del, L858R, and double mutants T790M/L858R and T790M/Del, respectively. Mavelertinib can be used for the research of non-small-cell lung cancer (NSCLC)[1][2][3][4].
BMS-605541 is a selective and orally active inhibitor of VEGFR-2 kinase with an IC50 value of 23 nM and Ki value of 49 nM. BMS-605541 inhibits the activity of Flk-1, VEGFR-1 and PDGFR-β with IC50 values of 40 nM, 400 nM and 200 nM, respectively. BMS-605541 can be used for cancer research[1].
Chromeceptin is an IGF signaling pathway inhibitor. Chromeceptin suppresses IGF2 at mRNA and protein levels in hepatocyte and HCC cells. Chromeceptin inhibits the Phosphorylation levels of AKT and mTOR[1].
UNC-CA359 is a potent epidermal growth factor receptor (EGFR) inhibitor, with an IC50 value of 18 nM. UNC-CA359 exhibits strong anti-tumor activity, can be used to Chordoma research[1].
CHMFL-ABL-053 is a potent, selective and orally available Bcr-Abl/Src/p38 kinase inhibitor with IC50 of 70/62/90 nM; no inhibitory activity against c-Kit (>10 uM); inhibits the proliferation of CML cell lines K562 (GI50=14 nM), KU812 (GI50=25 nM), and MEG-01 (GI50=16 nM); completely suppresses tumor progression in the K562 cells inoculated xenograft mouse model with 50 mg/kg/day dosage treatment.
EGFR-IN-16 (compound 3) is a potent EGFR inhibitor with pIC50 of 4.85 and 4.74 for EGFR and HER-2, respectively[1].
BTK-IN-12 is a potent BTK inhibitor with IC50s of 1.2 nM and 0.8 nM for wild-type BTK or mutated BTK (C481S), respectively (WO2022037649A1; compound 8)[1].
TG 100801 is a prodrug that generates TG 100572 by de-esterification in development to treat age-related macular degeneration. TG 100572 is a multi-targeted kinase inhibitor which inhibits receptor tyrosine kinases and Src kinases; has IC50s of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, 0.2 for VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, Fgr, Fyn, Hck, Lck, Lyn, Src, Yes, respectively.
RK-24466 (KIN 001-51) is a potent and selective Lck inhibitor; inhibits Lck (64-509) and LckCD isoforms with IC50s of less than 1 and 2 nM, respectively.
BIIB091 is a highly selective, reversible BTK inhibitor for treating autoimmune diseases.
c-Met-IN-12 (compound 4r) is an orally active, potent and selective type II c-Met kinase inhibitor, with an IC50 of 10.6 nM. c-Met-IN-12 displays high inhibitory effects (inhibition rate > 80% in 1 μM) against AXL, Mer and TYRO3 kinases. c-Met-IN-12 can be used a scaffold for further kinase selectivity enhancement. c-Met-IN-12 shows antitumor efficacy[1].
TL02-59 is an orally active, selective Src-family kinase Fgr inhibitor with an IC50 of 0.03 nM. TL02-59 also inhibits Lyn and Hck with IC50s of 0.1 nM and 160 nM, respectively. TL02-59 potently suppresses acute myelogenous leukemia (AML) cell growth[1].
PDGFR Tyrosine Kinase Inhibitor III (PDGF Receptor Tyrosine Kinase Inhibitor III), a multikinase inhibitor, inhibits PDGFR, EGFR, FGFR, PKA, and PKC, respectively. PDGFR Tyrosine Kinase Inhibitor III can be used for the research of amyotrophic lateral sclerosis[1].
AG-494 (Tyrphostin AG 494) is a potent and selective EGFR tyrosine kinase inhibitor (IC50=0.7 μM). AG-494 inhibits the autophosphorylation of EGFR, ErbB2, HER1-2 and PDGF-R with IC50s 1.1, 39, 45 and 6 μM, respectively. AG-494 blocks Cdk2 activation and inhibits EGF-dependent DNA synthesis[1][2][3].
PLX5622 is a highly selective brain penetrant and oral active CSF1R inhibitor, for extended and specific microglial elimination, preceding and during pathology development. PLX5622 demonstrates desirable PK properties in varies animals[1].
T338C Src-IN-2 is a potent mutant c-Src T338C kinase inhibitor with IC50 of 317 nM; also inhibits T338C/V323A and T338C/V323S with IC50 of 57 nM/19 nM.
MK8033 Hcl is a novel and specific dual ATP competitive c-Met/Ron inhibitor (IC50=1 nM Wt c-Met) under investigation as a treatment for cancer.IC50 Value: 1 nM (Wt c-Met); 2.0 nM (c-Met N1100Y) [1]Target: c-Metin vitro: MK-8033 binds 3-fold more tightly to phosphorylated c-Met kinase domain (Kd= 3.2 nM) than to its unphosphorylated counterpart (Kd = 10.4 nM). Signigicantly, MK-8033 potently inhibits kinase activity of three oncogenic c-Met activation loop mutants, Y1230C, Y1230H, and Y1235D (IC50s ranging from 0.6 to 1 nM at 50 uM ATP) in addition to other c-Met activating mutants N1100Y and M1250T. MK-8033 potently inhibited GTL-16 proliferation with an IC50 of 582 ± 30 nM. By contrast the HCT116 cell line, which does not harbor basal c-Met activation, was not inhibited by MK-8033 (IC50 > 10000 nM) [1]. MK-8033 radiosensitized the high-c-Met-expressing EBC-1 and H1993 cells but not the low-c-Met-expressing cell lines A549 and H460. However, irradiation of A549 and H460 cells increased the expression of c-Met protein at 30 minutes after the irradiation. Subsequent targeting of this up-regulated c-Met by using MK-8033 followed by a second radiation dose reduced the clonogenic survival of both A549 and H460 cells. MK-8033reduced the levels of radiation-induced phosphorylated (activated) c-Met in A549 cells [2].in vivo: MK-8033 was orally dosed in GTL-16 tumor xenograft bearing mice. Mice were euthanized 1 h after dosing and tested for p-Met (Y1349) in tumors and MK-8033 concentrations in plasma. At 100 mg/kg,essentially complete inhibition of p-Met (Y1349) was achieved. An in vivo IC50 of 1.3 uM was deduced from the relationship between plasma MK-8033 level and Met pY1349. Treatment with escalating dosed of MK-8033 for 21 days lead to antitumor efficacies in a dose-dependent manner. Dosing at 3, 10, 30, and 100 mg/kg resulted in 22, 18, 57, and 86% tumor growth inhibition, respectively, relative to tumor from vehicle-treated mice.
DYRKs-IN-2 (Example 132) is a potent DYRKs inhibitor with IC50s of 30.6 nM and 12.8 nM for DYRK1B and DYRK1A, respectively. DYRKs-IN-2 has antitumor activity[1].