EGFR Inhibitor

PROTAC EGFR degrader 9 (Compound C6) is an orally active CRBN-based PROTAC EGFR degrader. PROTAC EGFR degrader 9 exhibits a DC₅₀ of 10.2 nM and a K_d of 240.2 nM against EGFR^{L858R/T790M/C797S}. PROTAC EGFR degrader 9 exhibits potent degradation activity against various EGFR mutants, while sparing the EGFRWT. (Blue: CRBN ligand (HY-A0003), Black: linker (HY-161613); Pink: EGFR inhibitor (HY-161537)).

Duligotuzumab (MEHD-7945A; RG 7597) is a humanized IgG-κ monoclonal antibody targeting EGFR. Duligotuzumab blocks the binding of ligands to these two receptors, inhibits downstream HER/ErbB, AKT and MAPK signaling pathways, induces antibody-dependent cellular cytotoxicity, reduces the proliferation and migration abilities of cancer cells, promotes apoptosis, exerts radiosensitizing effects, and reverses EGFR resistance in cancer cells. Duligotuzumab can be used in tumor-related research.

PDZ1i (113B7) is a inhibitor of MDA-9/Syntenin, with selective binding to the PDZ1 domain. PDZ1i inhibits radiation-induced invasion of glioblastoma (GBM) cells, radiosensitizes GBM cells, and impairs GBM-related signaling pathways (including Src/EphA2, EGFRvIII/FAK, and NF-κB). PDZ1i reduces radiation-induced secretion of invasion-related proteases (MMP-2, MMP-9, ADAM9). PDZ1i shows anti-tumor effects in nude mice bearing intracranial U1242-luc xenografts or GBM xenografts. PDZ1i can be used for the study of glioblastoma (GBM), breast cancer and prostate cancer.

Myristicine is an orally bioavailable serotonin receptor antagonist and weak monoamine oxidase (MAO) inhibitor. Myristicine also exerts anti-cancer effects on gastric cancer cells by inhibiting the EGFR/ERK signaling pathway. Myristicine is the main component of nutmeg essential oil and has anti-cancer, anti-proliferative, antibacterial, anti-inflammatory and apoptosis-inducing effects. Myristicine abuse can produce hallucinogenic effects, organ damage, etc.

NSC689857 is a potent EGFR and SCF^SKP2 inhibitor with an IC₅₀ value of 36 μM for Skp2-Cks1. NSC689857 can inhibit p27 ubiquitylation (IC₅₀=30 μM). NSC689857 has varied activity across cancer types, with more activity against leukemia cell lines than others.

Mogroside IV-A is a triterpene glycoside found in Siraitia and acts as a PLSCR1 inhibitor. Mogroside IV-A inhibits PLSCR1-promoted EGFR phosphorylation and downstream MAPK signaling activation. Mogroside IV-A inhibits TPA (HY-18739)-induced activation of viral early antigen (EBV-EA). Mogroside IV-A enhances the anticancer effect of Epirubicin (HY-13624) and reverses acquired resistance of cells to Epirubicin. Mogroside IV-A is used in research related to triple-negative breast cancer and herpesvirus infection.

Theliatinib (Xiliertinib) is a potent, ATP-competitive, orally active and highly selective EGFR inhibitor with a K_i of 0.05 nM and an IC₅₀ of 3 nM. Theliatinib has an IC₅₀ of 22 nM for EGFR T790M/L858R mutant. Theliatinib shows >50-fold selectivity for EGFR than other kinases. Theliatinib is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Lazertinib (YH25448; GNS-1480) mesylate is an orally active, blood-brain barrier permeable third-generation EGFR tyrosine kinase inhibitor, as well as an ABCB1/ABCG2 inhibitor and a TRPA1 activator. Lazertinib mesylate exhibits IC₅₀ values of 0.4 mM and 0.2 mM against human ABCB1 and ABCG2, respectively. By inhibiting mutant EGFR signaling, EGFR phosphorylation and the downstream ERK/AKT pathway, as well as upregulating surface expression of EGFR/MET, Lazertinib mesylate induces cell cycle arrest, apoptosis, spontaneous calcium responses, hyperexcitability of dorsal root ganglion (DRG) neurons, and TRPA1-dependent pain-like behaviors. Lazertinib mesylate competitively binds to the substrate-binding sites of ABCB1/ABCG2, stimulates their ATPase activity without altering their expression or plasma membrane localization, thereby enhancing ADCC activity, acting as a chemosensitizer, and reversing ABCB1-mediated multidrug resistance. It exerts antitumor activity as a single agent or in combination with other drugs. Lazertinib mesylate is applicable to research related to non-small cell lung cancer, multidrug-resistant cancers, and paresthesia.

Oritinib (SH-1028), an irreversible third-generation EGFR TKI, overcomes T790M-mediated resistance in non-small cell lung cancer. Oritinib (SH-1028), a mutant-selective inhibitor of EGFR kinase activity, inhibits EGFR^WT, EGFR^L858R, EGFR^L861Q, EGFR^L858R/T790M, EGFR^d746-750 and EGFR^{d746-750/T790M} kinases, with IC₅₀s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM, respectively.

PP 3 (Compound 3) is an EGFR tyrosine kinase inhibitor with an IC₅₀ of 2.7 μM.

CL-387785 (EKI-785; WAY-EKI 785) is an orally active EGFR inhibitor with an IC₅₀ of 370 pM. CL-387785 inhibits EGF-stimulated EGFR autophosphorylation with an IC₅₀ of approximately 5 nM. CL-387,785 exerts selective inhibition on cell lines overexpressing EGFR or c-erbB-2, whereas it shows weak inhibitory effects on cell lines with low expression of these two receptors. CL-387785 effectively induces cell cycle arrest and apoptosis. CL-387785 can be used for the research of non-small cell lung cancer and autosomal recessive polycystic kidney disease.

Peruvoside is a potent inhibitor of Src, PI3K, JNK, STAT, and EGFR. Peruvoside induces apoptosis and autophagy and possesses a broad spectrum of anticancer activity in breast, lung, liver cancers and leukemia. Peruvoside is a broad-spectrum and potent antiviral activity against positive-sense RNA viruses. Peruvoside sensitizes Gefitinib (HY-50895)-resistant tumour cells (A549, PC9/gef and H1975) to Gefitinib.

BAY 2476568 is a potent and mutant-selective inhibitor targeting EGFR exon20 insertion variants. BAY 2476568 potently inhibits the kinase activity of EGFR exon20 insertion mutants (insASV, insSVD, insNPG) with IC₅₀ values of 0.09 nM, 0.21 nM, and 0.11 nM, respectively. BAY 2476568 inhibits EGFR (Y1068) phosphorylation and reduces the phosphorylation of ERK1/2 and Akt (S473) in Ba/F3 cells expressing EGFR exon20 insertion mutants (insASV, insSVD). BAY 2476568 can be used for the study of non-small cell lung cancer (NSCLC) driven by EGFR exon20 insertion mutations.

E260 is a Fer/FerT kinase inhibitor.

ALK-IN-1 is an orally active, blood-brain barrier-permeable ALK and EGFR inhibitor. ALK-IN-1 binds to and inhibits ALK kinase, ALK fusion proteins, and wild-type and mutant EGFR variants, thereby disrupting their corresponding signaling pathways. ALK-IN-1 can suppress the growth and proliferation of tumor cells and exhibits potential inhibitory activity against mutant EGFR. ALK-IN-1 can be used in the research of non-small-cell lung cancer.

WZ4002 is a mutant selective EGFR inhibitor with IC₅₀s of 2, 8, 3 and 2 nM for EGFR^L858R, EGFR^L858R/T790M, EGFR^E746_A750 and EGFR^{E746_A750/T790M}, respectively.

PF-06459988 is an orally activity, irreversible and mutant-selective inhibitor of EGFR mutant forms. PF-06459988 demonstrates high potency and specificity to the T790M-containing double mutant EGFRs. PF-06459988 can be used for the research of cancer.

CH7233163 is a noncovalent ATP-competitive inhibitor for EGFR-Del19/T790M/C797S. CH7233163 can overcome Osimertinib (HY-15772)-Resistant EGFR-Del19/T790M/C797S mutation. CH7233163 blocks the EGFR phosphorylation in the Del19/T790M/C797S_NIH3T3 cells. CH7233163 has antitumor activities.

Fepixnebart (LY3016859) is a humanized monoclonal hIgG4 antibody, which binds and neutralizes only TGFα and epiregulin with high affinity. Fepixnebart can be used for the study of diabetic nephropathy and broad-spectrum chronic pain, including diabetic peripheral neuropathic pain (DPNP), signs and symptoms of osteoarthritis (OA), and chronic low back pain (CLBP).

Laprituximab (J2898A) is a humanized IgG1 anti-EGFR antibody that can be used for the synthesis of ADC IMGN289.