ONO-7579 (ONO7579) is a novel potent, selective, orally available pan-TRK inhibitor.BDNF significantly increased TRKB phosphorylation in GBC cells and the effects were abrogated by ONO-7579, suppress proliferation in a dose-dependent manner in TYGBK-1 cells.ONO-7579 inhibited BDNF/TRKB-induced migration and invasiveness, particularly in GBC cells harboring wild-type KRAS.ONO-7579 reduced invasiveness of gallbladder cancer (GBC) cells through inhibiting epithelial–mesenchymal transition (EMT) via the extracellular signal-regulated kinase (ERK) or protein kinase B (AKT) pathway.

NSC81111 is a highly potent EGFR-TK inhibitor with IC50 of 0.15 nM; NSC81111 displays stronger antiproliferative activities than erlotinib with IC50 values of <10 uM overexpressed EGFR-TK cancer cell lines: A431 and HeLa.

MU1787 is a potent, highly selective HIPK inhibitor with IC50 of 285/123/283 nM for HIPK1/2/3, repectively.MU1787 is highly selective across the kinome in a broad panel of 373 human kinases, does not inhibits HIPK4 at 10 uM.

MU1700 is a potent, selective ALK1 (ACVRL1) and ALK2 (ACVR1) protein kinase inhibitor with IC50 of 13 and 6 nM, respectively.MU1700 inhibits only ALK1/2/6 and no additional off targets by kinome-wide screening against 369 protein kinases at 1 uM.MU1700 affects phosphorylation of SMAD1/5/8 that corresponds to BMP branch of signalling wchich is mediated also by ALK1/2 kinases.MU1700 is suitable chemical probe for in vivo disease models, and has remarkably high brain penetrance (mice, PO, 1 g/kg).

M4K2234 is a potent, selective ALK1 (ACVRL1) and ALK2 (ACVR1) protein kinase inhibitor with IC50 of 7 and 14 nM, respectively.M4K2234 inhibits only ALK1/2 and one additional off target (TNIK) by kinome-wide screening against 375 protein kinases at 1 uM.M4K2234 demonstrated in cell based target engagement assays with an IC50 of 83nM for ALK1 and 13 nM for ALK2.M4K2234 exhibits only very weak potency against ALK4/5.M4K2234 affects phosphorylation of SMAD1/5/8 that corresponds to BMP branch of signalling which is mediated, besides others, also by ALK1/2 kinases.M4K2234 has only a very weak effect on SMAD2/3 phosphorylation that corresponds to TGF beta branch of signalling which is mediated mostly via ALK4/5/7.

LS-106 is a novel, fourth‐generation EGFR inhibitor against C797S mutation, targeting both EGFR19del/T790M/C797S and EGFRL858/T790M/C797S with selectivity over EGFRwt.LS-106 potently and dose‐dependently inhibited the kinase activity of EGFR19del/T790M/C797S, EGFRL858R/T790M/C797S, EGFRL858R/T790M, and EGFR19del/T790M with IC50 values of 2.4 nM, 3.1 nM, 7.3 nM, and 74.1 nM, respectively.LS-106 exhibited much weaker effect against EGFRwt (IC50=151.5 nM) and EGFR19del (IC50=402.9 nM).LS‐106 not only strongly inhibited the EGFR‐C797S-mutant kinase but also inhibited some other kinases, such as RET, ACK1, and PDGFR‐β.LS‐106 not only inhibited the proliferation of BaF3‐EGFR19del/T790M cells (IC50= 0.09 uM) but also showed over 30‐fold stronger antigrowth activity than osimertinib in BaF3‐EGFR19del/T790M/C797S (IC50= 0.09 uM) and BaF3‐EGFRL858R/T790M/C797S (IC50= 0.12 uM) cells, respectively, elicits significant cell apoptosis in EGFR–triple‐mutant cells.Oral administration of LS‐106 (30 and 60 mg/kg) potently inhibited tumor progression in PC‐9‐OR NSCLC xenograft model with TGI of 83.5% and 136.6%, respecitvely.

LDN192960 (LDN 192960) is a highly potent and selective DYRK2 inhibitor with IC50 of 13 nM toward DYRK2 at 50 uM ATP.LDN192960 suppresses Thr25 RPT3 phosphorylation in a dose-dependent manner in HEK293T cells transiently overexpressing DYRK2-FLAG, with maximal effects at 1-10 uM.LDN192960 does not inhibit any of the 130+ kinases including other CMGC kinase family members that are closely related to the DYRKs.LDN192960 binds to the ATP-binding pocket of DYRK2, also potently inhibits DYRK1A, DYRK3 and Pim with IC50 of <3, 122 and 10 nM, respectively.LDN192960 perturbs proteasome activity, induces cell death, and impedes proliferation and invasion on MDA-MB-468 cells.LDN192960 impedes MM progression and delays myeloma-mediated bone degeneration.LDN192960 induces cytotoxicity in bortezomib-resistant MM, both in cells and in vivo. significantly alleviates tumor burden in standard and PDX TNBC models.

KIN-8194 (KIN8194) is a highly potent dual HCK and BTK inhibitor with IC50 of <0.495 and 0.915 nM, respectively.KIN-8194 demonstrated greater selectivity compared with A419259 with no KIT, RET, PDGFRA, EPHB6, or CDPK1 inhibition.KIN-8194 binds to gatekeeper residue Thr333 of HCK, but not to Cys481 of BTK.KIN-8194 shows robust inhibition of both HCK and BTK activity in MYD88-mutated cells, showed robust inhibition of HCK Tyr410 phosphorylation; inhibits the growth and survival of MYD88-mutated WM and ABC DLBCL cells.KIN-8194 overcomes ibrutinib resistance relatedto BTK Cys481Ser-expressing MYD88-mutated B-cell lymphoma cells, synergizes with the BCL-2 inhibitor venetoclax.KIN-8194 shows superior activity over ibrutinib in MYD88-mutated TMD-8 ABC DLBCL xenograft mouse model.KIN-8194 is active against ibrutinib resistance in BTK Cys481Ser -expressing ABC DLBCL xenograft mouse model.

JWD-065 is a potent small molecule HIPK2 kinase inhibitor, blocks HIPK2 phosphorylation on S359/T360 and JNK activation in HEK293 cells and attenuates ER stress-induced cell death with EC50 of 641 nM.

JS25 is a potent, selective, covalent TEC family of non-receptor tyrosine kinases (BTK, ITK, TXK and BMX) inhibitor with IC50 of 3.5 and 5.8 nM for BMX and BTK, respectively.JS25 displays a strong binding affinity against all the members of TEC family, covalently inhibits BMX at Cys496. JS25 demonstrates intracellular target engagement in HEK293 cells (IC50=44.8 nM), 10 times greater than BMX-IN-1.JS25 inhibits androgen-receptor positive prostate-cancer cells with GI50 of 6.6 uM.JS25 shows synergistic anti-proliferative activity in LNCaP cells in combination with AKT1/2 (AKT inhibitor), Flutamide (androgen receptor antagonist) and LY293002 (PI3K inhibitor).

JS24 is a potent, selective, covalent TEC family of non-receptor tyrosine kinases (BTK, ITK, TXK and BMX) inhibitor with IC50 of 7.5 and 11.1 nM for BMX and BTK, respectively.JS24 displays a strong binding affinity against all the members of TEC family, covalently inhibits BMX at Cys496.JS24 inhibits androgen-receptor positive prostate-cancer cells with GI50 of 1.5 uM.JS24 shows synergistic anti-proliferative activity in LNCaP cells in combination with AKT1/2 (AKT inhibitor), Flutamide (androgen receptor antagonist) and LY293002 (PI3K inhibitor).

JBJ-08-178-01 is a potent, selective and covalent HER2 inhibitor with IC50 of 2.21 nM and 7.04 nM for HER2 WT and EGFR WT, targets multiple HER2 activating mutations, including exon 20 insertions as well as amplification (IC50 values<50 nM).JBJ-08-178-01 maintained potency against non-insertion mutations, including S310F, L755S, V777L, V842I, and exon 19 indel (755_757LREdelinsRP) of HER2.JBJ-08-178-01 exhibited a much greater degree of HER2-selectivity in Ba/F3 cell lines than in biochemical assays, owing to weak growth inhibition against Ba/F3 cells with WT EGFR (IC50=368 nM).JBJ-08-178-01 showed strong antitumoral activity in HER2- mutant or amplified cancers in vitro and in vivo.Treatment with JBJ-08-178-01 also led to a reduction in total HER2 by promoting proteasomal degradation of the receptor.JBJ-08-178-01 is a selective, dual-action inhibitor and destabilizer of HER2 with potential efficacy and tolerance against NSCLC harboring HER2 genetic alterations or amplification.

HJ-01 is a small molecule that disrupts PTPσ-Trk interaction, enhances Trk signaling, and promotes sympathetic nerve regeneration over chondroitin sulfate proteoglycans (CSPGs).

GSK143 is a highly potent, selective, orally efficacious Syk inhibitor with pIC50 of 7.5, >600-fold selective over ZAP-70; inhibits anti-IgM induced Erk1/2 phosphorylation in Ramos cells with pIC50 of 7.1, and anti-IgM induced CD69 surface expression in primary B cells with pIC50 of 6.6; shows good efficacy in the rat Arthus model.

FGFR4-IN-2 is a potent, selective, covalent FGFR4 inhibitor with cellualr IC50 of 8.8 nM, 100-fold selectivity over FGFR2.FGFR4-IN-2 potently and selectively inhibit FGFR4 signaling through covalent modification of Cys552.FGFR4-IN-2 induces tumor regression in preclinical models of orthotopic and sorafenib-resistant HCC.

FF-10101 (FF10101) is a potent, selective, and irreversible FLT3 inhibitor with IC50 of 0.14 nM (FLT3 Wt), covalent binds to the C695 residue of FLT3.FF-10101 potently inhibited the phosphorylation of FLT3-ITD than that of FLT3-ITD-C695S (IC50 values 2.4 nM and 79 nM, respectively).FF-10101 potently and selectively inhibits the growth of mutant FLT3-expressing leukemia cells in vitro (MV4-11 c ell, IC50=0.83 nM), potently inhibits kinase activities of wild-type FLT3 and FLT3-D835Y with IC50 values of 0.20 nM and 0.16 nM, respectively.FF-10101 demonstrated high kinase selectivity to wild-type FLT3 with >30-fold margins against the other kinases except for FMS and KIT with IC50 values of 0.94 nM and 2.0 nM, respectively.FF-10101 showed growth inhibitory effects on all tested types of FLT3-TKD mutation- and FLT3-ITD with D835Y, Y842C, Y842H, or F691L mutation-expressing 32D cells with GI50 values from 0.43 nM to 6.1 nM.FF-10101 (2, 5, and 10 mg/kg) demonstrated anti-leukemic effects in in vivo models, FF-10101 more potently inhibited the growth of tumors with FLT3-ITD-D835Y and FLT3-ITD-F691L than quizartinib.

ER-001259851-000 is a potent, selective, orally active Axl inhibitor with IC50 of 5.2 nM in cell free assays, displays >35-fold selectivity against Mer (IC50=190 nM).ER-001259851-000 shows a promising pharmacokinetic profile in mice.

EMI66 (EMI-66) is a small molecule that attenuates RTK expression and signalling and alters the electrophoretic mobility of Coatomer Protein Complex Beta 2 (COPB2, binding Kd=1.51 uM) in lung cancer cells.EMI66 affects the subcellular localization of EGFR and COPB2, altering the endoplasmic reticulum (ER) stress response pathway, resulting in growth inhibition of mutant EGFR lung cancer cells and organoids.EMI66 inhibited total EGFR and MET levels, activation, and downstream signalling at lower concentrations than EMI1, also binds to recombinant COPB2 protein with an increased affinity compared to EMI1.EMI66 exerts an anti-proliferative effect (EC50=3-5 uM) on primary lung cancer organoid models, including XDO-137 (EGFR ex19del), PDXO-4000 (EGFR ex19del) and XDO-344 (wild-type EGFR).

CXF-009 is a potent, specific, dual-warhead covalent inhibitor of FGFR4 (IC50=48 nM), forms dual-warhead covalent bonds with two cysteine residues in FGFR4.CXF-009 forms covalent bonds with FGFR4(C477A) and FGFR4(C552A), respectively; display weak inhibition against FGFR1-3 with IC50 of 2579 nM, 2408 nM, and 977 nM.CXF-009 shows inhibitory effect agaginst FGFR4 muntants FGFR4(C477A), FGFR4(C552A), and FGFR4(C477A, C552A) with IC50 of 193 nM, 602 nM, and 1528 nM, respectively.CXF-009 inhibited the growth of Ba/F3 cells transformed with FGFR1-4 with IC50 values of 1562 nM, 1971 nM, 777 nM, and 38 nM, respectively.CXF-009 is slightly more reactive to GSH than PRN1371.

BJG-03-025 is a potent, highly selective FAK tyrosine kinase inhibitor with biochemical IC50 of 20.2 nM.BJG-03-025 demonstrates excellent kinome selectivity was profiled by KINOMEscan screening, PLK1 proved to be a false positive with IC50 of 8.3 uM, 100-300-fold selective for FAK.BJG-03-025 displays antiproliferative activity in three-dimensional (3D)-breast and gastric cancer models and impacts cellular signaling and migration.BJG-03-025 decreased phosphorylated FAK (pFAK Y397) in gastric cancer CDH1–/–RHOAY42C/+ organoid model, decreased aberrant signaling and proliferation of gastric cancer organoids.

BI-4020 (BI 4020) is a potent, next generation, wt-sparing inhibitor of EGFR mutant T790M and/or C797S, and EGFRdel19 T790M C797S (0.2 nM).BI-4020 inhibits not only the triple mutant EGFRdel19 T790M C797S variant but also the double mutant EGFRdel19 T790M and primary mutant EGFRdel19 while sparing activity against EGFRwt.BI-4020 shows high potency on EGFR mutant cells, high kinome selectivity, and good DMPK properties.BI-4020 exhibites tumor regressions in the human PC-9 (EGFRdel19 T790M C797S) triple mutant NSCLC xenograft model in mice.

AZD1332 is a potent, selective, ATP-competitive neurotrophic tyrosine kinase receptor (NRTK;TRK) inhibitor with IC50 of <10 nM; inhibits phosphorylation of TrkA/B/C in MCF10A cells overexpressing TrkA and NIH3T3 cells over expressing TrkA, TrkB, or TrkC with IC50 of <5 nM, inhibits a panel Baf3 survival driven by TrkA, TrkB, or TrkC with EC50 of 2 nM, AZD 1332 is orally available.

ASK120067 is a novel third-generation inhibitor of EGFR T790M (L858R/T790M IC50=0.3 nM, T790M IC50=0.5 nM), with selectivity over EGFR WT (IC50=6 nM).ASK120067 potently inhibited the EGFR L858R/T790M and EGFR T790M resistant mutants, with IC50 of 0.3 nM and 0.5 nM, respectively, as well as the EGFR exon19del sensitizing mutant (IC50= 0.5 nM).ASK120067 also displayed a favorable selectivity profile against a panel of 258 kinases.ASK120067 selectively inhibits the growth of EGFR-mutant cell lines and induces apoptosis, with IC50 values of 12 nM, 6 nM and 2 nM against NCI-H1975, PC-9, and HCC827 cells, respectively.ASK120067 dose-dependently inhibited EGF-induced EGFR L858R/T790M phosphorylation and consequent activation of the downstream molecules AKT and ERK in NCI-H1975 cells, with similar or even more effective potency than osimertinib.ASK120067 (5, 10 mg/kg once daily) demonstrated profound and selective antitumor efficacy in EGFR-mutant xenograft models in vivo.

Alphastatin-C is a 14-amino acids peptide consisting of a C-terminal fragment of the α-chain of Fgn, is a potent inhibitor of bFGF induced endothelial cell (HUVEC-CS) activation in vitro.Alphastatin-C inhibits tumor angiogenesis and reduces melanoma tumor growth, inhibits the chorioallantoic membrane (CAM) angiogenesis in chick model.Alphastatin-C efficiently reduces tumor number and volume in a melanoma mice model, due to the impairment of tumor neovascularization in treated mice.Alphastatin-C is an efficient new antiangiogenic FGF-associated agent in vitro, and inhibitor of embryonic and tumor vascularization in vivo, also is an arteriogenic agent

ALK2 R206H inhibitor 23 is a potent and selective inhibitor of Activin Receptor-Like Kinase-2 (ALK2/ACVR1) with IC50 of 8 nM for mutant ALK2 R206H.ALK2 R206H inhibitor 23 displays >15-fold selectivity over ALK1/ALK3, and >100-fold over ALK5/ALK6.

AL906 (AL 906) is a novel potent, selective EGFR inhibitor with IC50 of 12 nM (EGFR phosphorylation).AL906 blocked EGF-induced EGFR phosphorylation at doses as low as 1 uM in EGF-stimulated OV90 and DU145 cells.AL906 growth inhibitory activity was superior to that of the clinical drug gefitinib.AL906 selectively inhibited the growth of the NIH3T3-EGFR and HER2 transfectants in isogenic NIH3T3 transfected cell panel.

SRI-37264 (SRI 37264) is a small molecule inhibitor of HIV-1 Nef-mediated activation of the myeloid Src-family kinase Hck, blocks HIV-1 replication in macrophages and disrupts MHC-I downregulation.

PRN473 (Atuzabrutinib, SAR 444727, PRN-473) is a potent, selective, covalent reversible BTK inhibitor.

Pyrotinib (SHR-1258) is a potent and selective EGFR/HER2 dual inhibitor with IC50 of 13/38 nM, respectively.

GSK3179106 (GSK-3179106, GSK 3179106) is a potent, selective, first-in-class and gut-restricted with IC50 of 0.4 and 11 nM in the biochemical assay and cellular assay respectively.