Nazartinib(EGF816) is a novel covalent inhibitor of mutant-selective EGFR; overcomes T790M-mediated resistance in NSCLC.

Selatinib is a reversible and orally active dual EGFR and ErbB2 inhibitor with IC50s of 13 nM and 22.5 nM, respectively. Selatinib has anticancer effects.

PD 174265 is a potent, cell-permeable, reversible, and selective inhibitor of EGFR with an IC50 of 450 pM.

RG-13022 is an inhibitor of epidermal growth factor (EGF) receptor kinase with an IC50 value of 1 µM in HT-22 cells.

Sapitinib(AZD8931) is a reversible, ATP competitive inhibitor of EGFR, ErbB2 and ErbB3 with IC50 of 4 nM, 3 nM and 4 nM respectively.

Theliatinib (HMPL-309) is a novel small molecule, EGFR tyrosine kinase inhibitor with potential antineoplastic and anti-angiogenesis activities.

SPH5030 is a selective, potent, and irreversible HER2 mutants inhibitor with IC50 of <1 nM against HER2 D769H, D769Y, V777L and R896C mutants.SPH5030 exhibits high relative HER2 selectivity compared with neratinib and pyrotinib.SPH5030 shows significant in vivo antitumor efficacy in xenograft mouse models, especially in a HER2 mutation A775_G776insYVMA xenograft mouse mode.

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.

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.

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.

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).

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.

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.

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.

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

Methyl 2,5-dihydroxycinnamate is an erbstatin analog and a stable, potent inhibitor of EGFR kinase activity.

EGFR-IN-28 is a potent EGFR inhibitor. EGFR-IN-28 has antitumor activity.

EGFR-IN-30 is a potent EGFR inhibitor with IC50s of 1-10 nM, <1 nM for EGFR (WT), EGFR (L858R/T790M/C797S), respectively. EGFR-IN-30 has potential for cell proliferative diseases, such as cancer research.

EGFR-IN-33 is a potent inhibitor of EGFR. EGFR-IN-33 is an anti-tumor drug with low toxic side effects. EGFR-IN-33 is an acrylamide derivative compound. Overexpression and mutation of the epidermal growth factor receptor (EGFR) has been clearly demonstrated to lead to uncontrollable cell growth and is associated with the progression of most cancer diseases, especially NSCLC. EGFR-IN-33 has the potential for the research of diseases associated with EGFR mutations (extracted from patent WO2021185348A1, compound 13).

EGFR-IN-35 is a potent inhibitor of EGFR. EGFR-IN-35 is an anti-tumor drug with low toxic side effects. EGFR-IN-35 is an acrylamide derivative compound. Overexpression and mutation of the epidermal growth factor receptor (EGFR) has been clearly demonstrated to lead to uncontrollable cell growth and is associated with the progression of most cancer diseases, especially NSCLC. EGFR-IN-35 has the potential for the research of diseases associated with EGFR mutations (extracted from patent WO2021185348A1, compound 11).

EGFR-IN-36 is a potent EGFR inhibitor with IC50s of 19.09 nM, 120.01 nM, 2.35 nM for EGFR (WT), HER2 (WT), HER2 (A775_G776insYVMA), respectively. EGFR-IN-36 has potential for wild and/or mutant EGFR and/or HER2 kinase mediated tumors research.

EGFR-IN-37 is a potent inhibitor of EGFR. EGFR-IN-37 is an anti-tumor drug with low toxic side effects. EGFR-IN-39 is an acrylamide derivative compound. Overexpression and mutation of the epidermal growth factor receptor (EGFR) has been clearly demonstrated to lead to uncontrollable cell growth and is associated with the progression of most cancer diseases, especially NSCLC. EGFR-IN-37 has the potential for the research of diseases associated with EGFR mutations (extracted from patent WO2021185348A1, compound 7).

EGFR-IN-38 is a potent inhibitor of EGFR. EGFR-IN-38 is an anti-tumor drug with low toxic side effects. EGFR-IN-33 is an acrylamide derivative compound. Overexpression and mutation of the epidermal growth factor receptor (EGFR) has been clearly demonstrated to lead to uncontrollable cell growth and is associated with the progression of most cancer diseases, especially NSCLC. EGFR-IN-38 has the potential for the research of diseases associated with EGFR mutations (extracted from patent WO2021185348A1, compound 4).

EGFR-IN-39 is a potent inhibitor of EGFR. EGFR-IN-39 is an anti-tumor drug with low toxic side effects. EGFR-IN-39 is an acrylamide derivative compound. Overexpression and mutation of the epidermal growth factor receptor (EGFR) has been clearly demonstrated to lead to uncontrollable cell growth and is associated with the progression of most cancer diseases, especially NSCLC. EGFR-IN-39 has the potential for the research of diseases associated with EGFR mutations (extracted from patent WO2021185348A1, compound 2).

EGFR-IN-31 is a potent inhibitor of EGFR. Overexpression and mutation of the epidermal growth factor receptor (EGFR) has been clearly demonstrated to lead to uncontrollable cell growth and is associated with the progression of most cancer diseases, especially NSCLC. EGFR-IN-31 has the potential for the research of diseases associated with EGFR mutations (extracted from patent WO2021185298A1, compound 2).

EGFR-IN-32 is a potent inhibitor of EGFR. Overexpression and mutation of the epidermal growth factor receptor (EGFR) has been clearly demonstrated to lead to uncontrollable cell growth and is associated with the progression of most cancer diseases, especially NSCLC. EGFR-IN-32 has the potential for the research of diseases associated with EGFR mutations (extracted from patent WO2021185297A1, compound 2).

HER2-IN-5 is a potent and orally active HER-2 inhibitor, example 10, extracted from patent WO2021164697.

EGFR-IN-29 is a potent EGFR inhibitor, example J-022, extracted from Patent WO2021160087.

(E)-AG 556 is a highly selective EGFR inhibitor and also blocks LPS-induced TNF-α production.

EGFR-IN-34 is a potent inhibitor of EGFR. EGFR-IN-34 is an anti-tumor drug with low toxic side effects. EGFR-IN-35 is an acrylamide derivative compound. Overexpression and mutation of the epidermal growth factor receptor (EGFR) has been clearly demonstrated to lead to uncontrollable cell growth and is associated with the progression of most cancer diseases, especially NSCLC. EGFR-IN-34 has the potential for the research of diseases associated with EGFR mutations (extracted from patent WO2021185348A1, compound 12).