Protein kinase inhibitor 4 (Compound 3) is a protein kinase inhibitor that inhibits TRK-A and ROS1 (IC50=3.0 nM and 104 nM respectively)[1].
UniPR1447 is Dual EphA2 and EphB2 antagonist, with an IC50 of 6.6 μM for EphA2−ephrin-A1 binding[1].
IRAK4-IN-21 (compound 17) is an orally active, potent and selective IRAK4 inhibitor with IC50 values of 5 and 56 nM for IRAK4 and TAK1, respectively. IRAK4-IN-21 effectively inhibits IL-23 production (IC50=0.17 µM) and can be used in studies of autoimmune diseases such as plaque psoriasis and psoriatic arthritis[1].
EGFR-IN-68 (Compound 8d) is a potent EGFR inhibitor with an IC50 of 0.33 μM. EGFR-IN-68 shows anticancer activity[1].
ASP5878 is an oral active and selective inhibitor of the fibroblast growth factor receptor (FGFR), with an IC50 of 3.5 nM for fibroblast growth factor receptor 4 kinase activity. ASP5878 has potential antineoplastic activity[1].
EGFR/HER2-IN-2 (Compound ZINC35560729) is a dual inhibitor of EGFR and HER2 with IC50 values of 5.02 µM and 0.83 µM against EGFR and HER2, respectively[1].
WH-4-023 is a potent and selective dual Lck/Src inhibitor with IC50 of 2 nM/6 nM for Lck and Src kinase respectively; little inhibition on p38α and KDR.
IGF-1R inhibitor-2 (example 121) is an insulin-like growth factor-1 receptor (IGF-1R) inhibitor. Downregulation of IGF-1R can reverse the transformed phenotype of tumor cells and potentially render them susceptible to apoptosis[1].
c-Fms-IN-6 is a potent inhibitor of c-FMS, with an IC50 of ≤10 nM for unphosphorylated c-FMS, also weakly inhibits unphosphorylated c-KIT and PDGFR (IC50, > 1 μM). Used in the research of autoimmune diseases[1].
DDR1-IN-6 is a selective Discoidin Domain Receptor family, member 1 (DDR1) inhibitor with an IC50 of 9.72 nM. DDR1-IN-6 inhibits auto-phosphorylation DDR1b (Y513) with an IC50 of 9.7 nM. DDR1-IN-6 has anti-cancer activity[1].
PF-04217903 methanesulfonate is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM, susceptible to oncogenic mutations (no activity to Y1230C mutant).IC50 value: 4.8 nM [1]Target: c-Metin vitro: Being more selective than staurosporine or PF-02341066, PF-04217903 displays >1000-fold selectivity for c-Met over a panel of 208 kinases, although more susceptible to oncogenic mutations of c-Met that attenuate potency than PF-02341066. In addition to WT c-Met, PF-04217903 displays similar potency to inhibit the activity of c-Met-H1094R, c-Met-R988C, and c-Met-T1010I with IC50 of 3.1 nM, 6.4 nM, and 6.7 nM, respectively, but has no inhibitory activity against c-Met-Y1230C with IC50 of >10 μM [1]. PF-04217903 in combination with sunitinib significantly inhibits endothelial cells, but not the tumor cells B16F1, Tib6, EL4, and LLC [2] PF-04217903 significantly inhibits the clonogenic growth of LXFA 526L and LXFA 1647L with IC50 values of 16 nM, and 13 nM, respectively, yielding an additive effect when in combination with cetuximab [3]. in vivo: Although unable to inhibit tumor growth in the sunitinib-sensitive B16F1 and Tib6 tumor models, the combination of PF-04217903 and sunitinib significantly inhibits tumor growth in sunitinib-resistant EL4, and LLC tumor models compared with sunitinib or PF-04217903 alone by significantly blocking vascular expansion, indicating a functional role for HGF/c-Met axis in the sunitinib-resistant tumors [2].
HG-7-85-01 is a type II ATP competitive inhibitor of wild-type and gatekeeper mutations forms of Bcr-Abl, PDGFRα, Kit, and Src kinases. HG-7-85-01 inhibits T315I mutant Bcr-Abl kinase, KDR and RET with IC50s of 3 nM, 20 nM and 30 nM, and is only weak or no inhibition of other kinases (IC50>2 μM). HG-7-85-01 inhibits the cell proliferation, which is mediated by the induction of apoptosis, and inhibition of cell-cycle progression[1].
Henatinib is an orally active small-molecule multikinase inhibitor that has demonstrated broad and potent antitumor activities. Henatinib inhibits the activity of VEGFR-2, c-kit, PDGFR with IC50 values of 0.6 nM, 3.3 nM and 41.5 nM, respectively. Henatinib significantly inhibits VEGFR-2 phosphorylation and its downstream signal pathway in human umbilical vein endothelial cells (HUVECs)[1].
FAK-IN-8 (compound 5h) is a FAK inhibitor (IC50=5.32 µM). FAK-IN-8 has good anti-proliferative activity and can be used in cancer research[1].
SCR-1481B1 (c-Met inhibitor 2) is a potent compound that has activity against cancers dependent upon Met activation and also has activity against cancers as a VEGFR inhibitor.
5'-Fluoroindirubinoxime (5’-FIO, compound 13), an Indirubin (HY-N0117) derivative, is a potent FLT3 inhibitor, with an IC50 of 15 nM[1].
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].
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].
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].
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].
PROTAC IRAK4 degrader-8 (compound 2) is a PROTAC targeting to IRAK4 (IC50=15.5 nM)[1].
CHMFL-EGFR-202 is a potent, irreversible inhibitor of epidermal growth factor receptor (EGFR) mutant kinase, with IC50s of 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases, respectively. CHMFL-EGFR-202 exhibits ∼10-fold selectivity for EGFR L858R/T790M against the EGFR wild-type in cells. CHMFL-EGFR-202 adopts a covalent “DFG-in-C-helix-out” inactive binding conformation with EGFR, with strong antiproliferative effects against EGFR mutant-driven nonsmall-cell lung cancer (NSCLC) cell lines[1].
Tucatinib (Irbinitinib; ARRY-380; ONT-380) is a potent and selective HER2 inhibitor with an IC50 of 8 nM.
Harmine is a natural dual-specificity tyrosine phosphorylation-regulated kinase ((DYRK)) inhibitor with anticancer and anti-inflammatory activities.
Crizotinib is a potent inhibitor of c-Met and ALK with an IC50 of 11 nM and 24 nM in cell-based assays, respectively.
AG 1295 is a selective platelet-derived growth factor receptor (PDGFR) tyrosine-kinase inhibitor. AG 1295 reduces neointimal formation in aortic allograft vasculopathy by inhibition of PDGFR-beta-triggered tyrosine phosphorylation[1][2].
ErbB-2-binding peptide (HER2-binding peptide) is a tumor-binding peptide. ErbB-2-binding peptide has the potential for cancer research[1].
Lucitanib (E-3810) is a novel dual inhibitor of VEGFR and FGFR, potently and selectively inhibits VEGFR1, VEGFR2, VEGFR3, FGFR1 and FGFR2 with IC50s of 7 nM, 25 nM, 10 nM, 17.5 nM, and 82.5 nM, respectively.
c-ABL-IN-2 is a potent inhibitor of c-Abl. Activation of c-Abl has been implicated in various diseases, notably cancer. c-ABL-IN-2 has the potential for the research of neurodegenerative diseases (amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) and cancer (extracted from patent WO2020260871A1, compound 25)[1].