EGFR/HER2

Genistin is an isoflavone found in a number of dietary plants like soy and kudzu. It was shown to stimulate estrogen-dependent breast cancer cell growth in vivo.

AEE788 is an orally bioavailable multiple-receptor tyrosine kinase inhibitor that inhibits phosphorylation of the tyrosine kinases of EGFR, HER2 and VEGF2.

Canertinib (CI-1033) is an irreversible tyrosine-kinase inhibitor with activity against EGFR (IC50 0.8 nM), HER-2 (IC50 19 nM) and ErbB-4 (IC50 7 nM).

ARRY334543 is a potent, orally active small molecule inhibitor of EGFR and ErbB-2.

Erlotinib is an epidermal growth factor receptor inhibitor (EGFR inhibitor). Erlotinib HCl was approved. Erlotinib binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. For the signal to be transmitted, two EGFR molecules need to come together to form a homodimer. These then use the molecule of ATP to trans-phosphorylate each other on tyrosine residues, which generates phosphotyrosine residues, recruiting the phosphotyrosine-binding proteins to EGFR to assemble protein complexes that transduce signal cascades to the nucleus or activate other cellular biochemical processes. When erlotinib binds to EGFR, formation of phosphotyrosine residues in EGFR is not possible and the signal cascades are not initiated.

Gefitinib is an EGFR inhibitor, which interrupts signaling through the epidermal growth factor receptor (EGFR) in target cells.

Afatinib (BIBW 2992) is an irreversible EGFR family inhibitor with IC50s of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively.

AG-1478 (Tyrphostin AG-1478) is an inhibitor of EGFR kinase with an IC50 value of 3 nM.

AV-412 is an EGFR/HER2 inhibitor that binds to and inhibits the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2), which may result in the inhibition of tumor growth and angiogenesis.

Neratinib (HKI-272) is a tyrosine kinase inhibitor.

AG 490 is a selective inhibitor of EGF receptor tyrosine kinase (IC50 values are 2 and 13.5 μM for EGFR and ErbB2 respectively). Also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.

Osimertinib (AZD-9291) is a third-generation EGFR inhibitor, showed promise in preclinical studies and provides hope for patients with advanced lung cancers that have become resistant to existing EGFR inhibitors.

Lapatinib is a dual tyrosine kinase inhibitor which interrupts the HER2 growth receptor pathway. Lapatinib is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively. Lapatinib induces ferroptosis and autophagic cell death.

Pelitinib (EKB-569) is a 3-cyanoquinoline pan-ErbB tyrosine kinase inhibitor with potential antineoplastic activity.

(-)-Epigallocatechin gallate is a potent anti-oxidant polyphenol flavonoid isolated from green tea.

BIBW2992 (Afatinib) is tyrosine kinase inhibitor (TKI) that irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases.

AZD8931 is an oral, equipotent inhibitor of ErbB1, ErbB2 and ErbB3 receptor signaling.

DM1-SMCC is DM1 with a reactive linker SMCC, which can react with antibody to make antibody drug conjugate.

SU-5402 is a potent and selective vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR) inhibitor (IC50 values are 0.02, 0.03, 0.51 and > 100 μM at VEGFR2, FGFR1, PDGFRβ and EGFR respectively).

CP-724714 is an orally available, small molecule, potent HER-2 tyrosine kinase inhibitor that inhibits HER2 kinase (IC50 3.8 ng/ml) .

Dacomitinib (PF299804, PF299) is a potent, orally available, irreversible inhibitor of tyrosine kinase human epidermal growth factor receptors (HER) 1 (EGFR), HER2, and HER4.

Poziotinib is an orally bioavailable, quinazoline-based pan epidermal growth factor receptor (EGFR or HER) inhibitor with potential antineoplastic activity.

Erlotinib hydrochloride is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR).

OSI-420 (Desmethyl Erlotinib,CP-473420) is an orally active EGFR tyrosin kinase inhibitor, which inhibits receptor tyrosine kinases (TKs) by inhibition of the intercellular domain .

Tyrphostin AG 879 is an inhibitor of the tyrosine kinase activity of nerve growth factor (NGF) TrkA.

AST-6 is a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, inhibits tumor growth both in vitro and in vivo

Chrysophanic acid (Chrysophanol) blocks proliferation of colon cancer cells by inhibiting EGFR/mTOR pathway.

CUDC-101 is a novel compound which inhibits multiple targets, which is designed to inhibit HDAC, EGFR and Her2.

Daphnetin is a coumarin analog that acts as an inhibitor of several protein kinases. It inhibits EGFR kinase (IC50 = 7.67 μM), PKA (IC50 = 9.33 μM), and PKC (IC50 = 25 μM), in vitro. The inhibition of EGFR kinase by daphnetin was competitive to ATP and non-competitive to the peptide substrate. Also acts as a potent antioxidant and anti-malarial agent.

Genistein, a soy isoflavone, is a multiple tyrosine kinases (e.g., EGFR) inhibitor which acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis.

Lapatinib is a dual tyrosine kinase inhibitor which interrupts the HER2 growth receptor pathway.

Mubritinib (TAK 165) is a potent EGFR and p34cdc2 inhibitor with IC50 of 6 nM and 0.2 μM, respectively. Mubritinib(TAK 165) also inhibits p33cdk2 and p33cdk5.

PD153035 is an extremely potent and specific inhibitor of the tyrosine kinase activity of EGFR.

WZ3146 is an inhibitor of EGFR receptor kinase mutants carrying a mutation in an active site gatekeeper residue (T790M) and is much less potent against wild-type EGFR kinase.

WZ4002 is EGFR inhibitor against EGFR T790M (mutation of the gatekeeper T790 residue) which is detected in 50% of clinically resistant patients to gefitinib or erlotinib.

WZ8040 is a novel EGFR inhibitors that suppress the growth of EGFR-T790M-containing cell lines and inhibit EGFR phosphorylation.

ARRY-380 is an ErbB-2 inhibitor that selectively binds to and inhibits the phosphorylation of ErbB-2, resulting in growth inhibition and death of ErbB-2-expressing tumor cells.

XL647 is an orally bioavailable small-molecule RTK inhibitor that binds to and inhibits several tyrosine receptor kinases that play major roles in tumor cell proliferation and tumor vascularization, including EGFR, HER2, ERBB2, VEGFR and EphB4.

SU-4313 is a small-molecule modulator of protein tyrosine kinases (PTKs). It inhibits multiple receptor tyrosine kinases with reported IC₅₀ values of 14.5 μM (PDGFR), 18.8 μM (FLK-1/VEGFR2), 11 μM (EGFR), 16.9 μM (HER2 kinase), and 8.0 μM (IGF-1R).

Through its multi-kinase inhibitory profile, SU-4313 modulates tyrosine kinase–mediated signal transduction pathways involved in the regulation of cell proliferation and growth. It is therefore commonly used as a research tool for investigating aberrant receptor tyrosine kinase signaling and proliferation-associated pathways.

MS154 is a novel E3 ligase cereblon-recruited degrader specifically targeting epidermal growth factor receptor (EGFR). It has demonstrated potent degradation of the EGFR L858R mutant in cancer cell lines with Kd values of 1.8 nM and 3.8 nM for wild-type and mutant EGFR, respectively. This selective degradation mechanism highlights its potential as an anticancer agent, particularly in lung cancer treatment. MS154 operates through an E3 ligase-dependent pathway, representing a promising therapeutic strategy for treating EGFR-driven malignancies.

Cucurbitacin IIa is a potent EGFR inhibitor with an IC50 of 1.455 nM, demonstrating effective modulation of the EGFR signaling pathway. This compound induces caspase-3-dependent apoptosis, downregulates survivin expression, and enhances autophagy, while disrupting the actin cytoskeleton and arresting the cell cycle at the G2/M phase. Additionally, Cucurbitacin IIa exhibits anti-inflammatory properties, making it a valuable tool for research into inflammation-related diseases, depression, and various cancers, including non-small cell lung cancer.

EGFR-IN-47 is a potent orally active inhibitor of the EGFR L858R/T790M/C797S mutations, with an IC50 of 0.01 μM. This compound effectively induces cell cycle arrest and promotes apoptosis in cancer cells. EGFR-IN-47 holds significant potential for research applications related to non-small cell lung cancer (NSCLC).

EGFR-IN-78 is a reversible inhibitor of the EGFR variant C797S-TK, classified as a 2-aminopyrimidine derivative. This compound induces apoptosis and exhibits significant anti-proliferative activity by inhibiting EGFR phosphorylation. Additionally, EGFR-IN-78 effectively arrests the cell cycle at the G2/M phase, making it a valuable tool for research applications focused on targeted cancer therapies.

EGFR-TK-IN-4 is a potent and selective inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFR-TK). It has been demonstrated to induce apoptosis in cancer cells and exhibits significant antitumor activity. This compound is suitable for studying EGFR signaling pathways and developing targeted therapies in oncology research.

YS-363 is a potent and selective orally active inhibitor of the epidermal growth factor receptor (EGFR), exhibiting IC50 values of 0.96 nM for wild-type and 0.67 nM for the L858R mutant form. This compound effectively induces G0/G1 cell cycle arrest and promotes apoptosis in target cells. YS-363 is valuable for research applications focused on cancer therapeutics and the molecular mechanisms of EGFR signaling.

Os30 is a potent fourth-generation EGFR inhibitor specifically targeting the EGFRC797S-TK mutation. With IC50 values of 18 nM and 113 nM for EGFRDel19/T790M/C797S TK and EGFRL858R/T790M/C797S TK, respectively, Os30 effectively inhibits EGFR phosphorylation, induces G1 phase cell cycle arrest, and triggers apoptosis in KC-0116 (BaF3-EGFRDel19/T790M/C797S) cells. This compound demonstrates significant antitumor activity in non-small cell lung cancer (NSCLC) harboring the EGFRC797S mutation, making it a valuable tool for cancer research and therapeutic exploration.

pan-HER-IN-2 is a reversible, orally active pan-HER inhibitor targeting multiple receptor tyrosine kinases, with IC50 values of 0.72 nM for EGFR, 2.0 nM for HER4, 8.2 nM for EGFRT790M/L858R, and 75.1 nM for HER2. This compound effectively induces apoptosis and exhibits significant antitumor activities. pan-HER-IN-2 is suitable for research applications focused on cancer therapy and the exploration of targeted treatments for HER family receptor-positive tumors.

Gefitinib dihydrochloride is a potent and selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, exhibiting an IC50 of 33 nM. This compound effectively inhibits EGF-stimulated tumor cell proliferation (IC50 of 54 nM) and prevents EGFR autophosphorylation, thereby blocking downstream signaling pathways. Gefitinib dihydrochloride is valuable for cancer research, particularly in the study of lung and breast cancers, due to its ability to induce autophagy and promote apoptosis in tumor cells.

Zorifertinib hydrochloride is a potent orally active inhibitor of the epidermal growth factor receptor (EGFR), demonstrating IC50 values of 0.3 nM, 0.2 nM, and 0.2 nM against wild-type EGFR, EGFR L858R, and EGFR exon 19 deletion variants, respectively. This compound is capable of inducing apoptosis in cancer cells and exhibits significant antitumor activity. Zorifertinib hydrochloride is primarily utilized in research related to non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC).

Famitinib malate is an orally active, multi-targeted kinase inhibitor primarily targeting c-kit, VEGFR-2, and PDGFRβ, with IC50 values of 2.3 nM, 4.7 nM, and 6.6 nM, respectively. This compound induces cell apoptosis and demonstrates significant anti-tumor activity in human gastric cancer cells and xenograft models. Famitinib malate is a valuable tool for research into cancer therapies and mechanisms of action.