EGFR Inhibitor

Dacomitinib (PF-00299804) is a specific and irreversible inhibitor of the ERBB family of kinases with IC₅₀s of 6 nM, 45.7 nM and 73.7 nM for EGFR, ERBB2, and ERBB4, respectively.

AG-1478 (Tyrphostin AG-1478) is a selective EGFR tyrosine kinase inhibitor with IC₅₀ of 3 nM. AG-1478 has antiviral effects against HCV and encephalomyocarditis virus (EMCV).

Patritumab (Human Anti-ERBB3 Recombinant Antibody) is a neutralizing monoclonal antibody to ERBB3. Patritumab shows a synergy with Cetuximab (HY-P9905), potently inhibits the phosphorylation of EGFR, HER2, HER3, ERK, and AKT. Patritumab also induces cell apoptosis and suppresses the growth of pancreatic, non-small cell lung cancer, and colorectal cancer xenograft tumors.

Osimertinib mesylate (AZD9291 mesylate) is a covalent, orally active, irreversible, and mutant-selective EGFR inhibitor with an apparent IC₅₀ of 12 nM against L858R and 1 nM against L858R/T790M. Osimertinib overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.

Lazertinib (YH25448; GNS-1480) 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 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 induces cell cycle arrest, apoptosis, spontaneous calcium responses, hyperexcitability of dorsal root ganglion (DRG) neurons, and TRPA1-dependent pain-like behaviors. Lazertinib 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 is applicable to research related to non-small cell lung cancer, multidrug-resistant cancers, and paresthesia.

BL-B01D1 (Izalontamab Brengitecan) is a bispecific antibody-drug conjugate (ADC) targeting EGFR and HER3, formed by conjugating the EGFR/HER3 bispecific antibody Izalontamab (HY-P99676) to a novel TOP-I inhibitor payload Deruxtecan 2-hydroxypropanamide (HY-153891) via a cleavable linker (Mc-Gly-Gly-Phe-Gly). BL-B01D1 binds to EGFR and HER3 on the surface of tumor cells, mediates endocytosis and releases the payload, inhibits topoisomerase I, blocks DNA replication and RNA synthesis, and disrupts DNA structure. BL-B01D1 induces cell cycle S-phase arrest, apoptosis, antibody-dependent cell-mediated cytotoxicity, and tumor cell death. BL-B01D1 can be used for cancer research.

Trastuzumab vedotin (MRG002; Trastuzumab MMAE) is an antibody-drug conjugate and cytotoxin targeting HER2, with a K_d of 7.50E-11 M for human HER2. After binding to HER2, Trastuzumab vedotin undergoes internalization and lysosomal trafficking, delivering a cytotoxic payload to HER2-expressing cells and inducing tumor regression in in vivo xenograft models with HER2-expressing tumors. The anti-tumor activity of Trastuzumab vedotin is enhanced when used in combination with anti-PD-1 antibodies, and it exhibits preclinical anti-tumor activity in drug-resistant breast cancer, gastric cancer, and urothelial carcinoma PDX models. Trastuzumab vedotin has low antibody-dependent cellular cytotoxicity activity and can be used in studies related to HER2-positive breast cancer, HER2-positive gastric cancer, and unresectable locally advanced or metastatic HER2-positive urothelial carcinoma.

Zenocutuzumab (MCLA-128) is a bispecific humanized IgG1 antibody containing two different Fab arms, targeting extracellular domains of HER2 and HER3.

Erlotinib (CP-358774) Hydrochloride is a selective, orally active EGFR tyrosine kinase inhibitor. Erlotinib Hydrochloride also acts as a substrate and inhibitor of OATP2B1, with an IC₅₀ of approximately 0.079 μM for inhibiting OATP2B1-mediated uptake of estrone 3-sulfate. Erlotinib Hydrochloride blocks EGFR phosphorylation, downstream signal transduction, as well as the growth and proliferation of cancer cells. Erlotinib Hydrochloride inhibits MMP-10-mediated renal injury, fibrotic lesions, the ERK1/2, GSK-3β and β-catenin signaling pathways, as well as the deposition of fibronectin, α-SMA, collagen and renal injury markers. Erlotinib Hydrochloride is metabolized via CYP3A to produce the active metabolite OSI-420. Erlotinib Hydrochloride can be used in research related to non-small cell lung cancer, gastric cancer, papillary renal cell carcinoma, EGFR inhibitor resistance and renal fibrosis.

Afatinib (BIBW 2992) dimaleate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC₅₀ values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFR^wt, EGFR^L858R, EGFR^L858R/T790M and HER2, respectively. Afatinib dimaleate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer.

Sapitinib (AZD-8931) is a reversible, ATP competitive EGFR inhibitor of with IC₅₀s of 4, 3 and 4 nM for EGFR, ErbB2 and ErbB3 in cells, respectively.

Chrysophanol (Chrysophanic acid) is a natural anthraquinone, which inhibits EGF-induced phosphorylation of EGFR and suppresses activation of AKT and mTOR/p70S6K.

Nimotuzumab is a humanized IgG1 monoclonal antibody targeting EGFR with a K_D of 0.21 nM. Nimotuzumab is directed against the extracellular domain of the EGFR blocking the binding to its ligands. Nimotuzumab, a strong antitumor agent, is cytolytic on target tumors by its capacity to cause antibody dependent cell mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC).

Firmonertinib (Alflutinib; Furmonertinib) is an orally active, mutant-selective, and highly brain penetrant EGFR inhibitor. Firmonertinib inhibits EGFR active mutations as well as the T790M acquired resistant mutation. Firmonertinib has the potential for the research of cancer diseases, especially advanced non-small cell lung cancer (NSCLC) with EGFR ex20ins mutation.

Izalontamab (SI-B001) is a bispecific anti-EGFR/HER3 monoclonal antibody with high selectivity for EGFR/HER3 heterodimer. Izalontamab can be used for the research of cancer.

Butein is a cAMP-specific PDE inhibitor with an IC₅₀ of 10.4 μM for PDE4. Butein is a specific protein tyrosine kinase inhibitor with IC₅₀s of 16 and 65 μM for EGFR and p60^c-src in HepG2 cells. Butein sensitizes HeLa cells to Cisplatin through AKT and ERK/p38 MAPK pathways by targeting FoxO3a. Butein is a SIRT1 activator (STAC).

Almonertinib (HS-10296) is an orally available, irreversible, third-generation EGFR tyrosine kinase inhibitor with high selectivity for EGFR-sensitizing and T790M resistance mutations. Almonertinib shows great inhibitory activity against T790M, T790M/L858R and T790M/Del19 (IC₅₀: 0.37, 0.29 and 0.21 nM, respectively), and is less effective against wild type (3.39 nM). Almonertinib is used for the research of the non-small cell lung cancer.

Delphinidin chloride is an anthocyanin isolated from berries and red wine. Delphinidin chloride exhibits endothelium-dependent vasodilation and anticancer activity. Delphinidin chloride also modulates JAK/STAT3 and MAPK signaling, thereby inducing apoptosis in HCT116 cells. Delphinidin chloride is also a potent inhibitor of EGFR (IC₅₀: 1.3 μM), shutting down downstream signaling cascades.

Pyrotinib (SHR-1258) is a potent and selective EGFR/HER2 dual inhibitor with IC₅₀s of 13 and 38 nM, respectively.

Gefitinib hydrochloride (ZD1839 hydrochloride) is a potent, selective and orally active EGFR tyrosine kinase inhibitor with an IC₅₀ of 33 nM. Gefitinib hydrochloride selectively inhibits EGF-stimulated tumor cell growth (IC₅₀ of 54 nM) and that blocks EGF-stimulated EGFR autophosphorylation in tumor cells. Gefitinib hydrochloride also induces autophagy. Gefitinib hydrochloride has antitumour activity.