egfr in 2

EGFR/ErbB-2 inhibitor-1 is a selective ErbB2/HER2 inhibitor that effectively blocks ErbB2 and HER2 signaling.

EGFR/HER2/DHFR-IN-2 (Compound 4b) serves as an inhibitor for EGFR, HER2, and DHFR, with IC50 values of 0.248, 0.156, and 0.138 μM, respectively. It exhibits anticancer activity, displaying IC50 values of 9.14, 7.33, 14.18, 24.87, 20.07, and 6.16 μM in Hep G2, HeLa, HEp-2, HCT 116, PC-3, and MCF7 cancer cell lines, respectively. Additionally, EGFR/HER2/DHFR-IN-2 has been shown to reduce the growth of breast cancer tumors [1].

PROTAC EGFR degrader 2 is a potent compound with exceptional antiproliferative activity, evidenced by its IC50 of 4.0 nM, and exhibits strong EGFR degradation activity with a DC50 of 36.51 nM. It is suitable for synthesizing nitroreductase (NTR)-responsive PROTACs [1].

EGFR/CDK2-IN-2 (compound 6a) serves as a dual inhibitor targeting both EGFR and CDK-2, exhibiting IC50 values of 19.6 nM and 87.9 nM, respectively. It promotes apoptosis in MCF-7 cells and halts cell cycle progression during the S phase. Additionally, this compound demonstrates notable anticancer activity, inhibiting MCF-7 cells with an IC50 of 0.39 μM [1].

ALK/EGFR-IN-2 is a potent dual inhibitor targeting ALK and EGFR, promoting apoptosis and G0/G1 cell cycle arrest in cancer cells. It effectively suppresses proliferation in H1975, PC9, and Baf3-EML4-ALK cancer cell lines, demonstrating IC50s of 0.0034, 0.0065, and 0.0018 μM, respectively [1].

Mutated EGFR-IN-2 is an inhibitor of mutant-selective EGFR.

EGFR/HER2/TS-IN-2 is a potent inhibitor of EGFR (IC50: 0.173 μM), HER2 (IC50: 0.125 μM) and TS (IC50: 1.12 μM). EGFR/HER2/TS-IN-2 exhibited cytotoxic effects on MDA-MB-231 cancer cells (IC50: 1.69 μM ).

EGFR-IN-2 is a non-covalent, mutation-selective and irreversible second-generation EGFR inhibitor.

EGFR/HER2-IN-2 (Compound ZINC35560729) is a dual EGFR and HER2 inhibitor that acts on both EGFR (IC50: 5.02 μM) and HER2 (IC50: 0.83 μM).

EGFR/HER2/CDK9-IN-2 are potent inhibitors of EGFR/HER2/CDK9, and they exhibited significant antitumor effects with IC50s of 145.35, 129.07 and 117.13 nM, respectively.

EGFRT790M/L858R-IN-2 is a potent, selective inhibitor of EGFRT790M/L858R, exhibiting IC50 values of 3.5 nM for EGFRT790M/L858R and 1290 nM for EGFR WT. This compound effectively decreases the expression of p-EGFR, P-AKT, P-ERK1/2, and induces apoptosis as well as cell cycle arrest in the G1 phase, demonstrating anti-cancer activity [1].

E07 Aptamer, targeting the human epidermal growth factor receptor (hEGFR), competes with epidermal growth factor (EGF) for binding to a unique epitope on EGFR. This aptamer not only binds to EGFR-expressing cells but also inhibits receptor autophosphorylation and thwarts tumor cell proliferation in three-dimensional matrices, positioning it as a useful tool for tumor disease research [1].

EGFR/ErbB-2/ErbB-4 inhibitor-2 (EGFR/ErbB2 Inhibitor) is a cell-permeable inhibitor of EGFR and c-ErbB2 (IC50s = 20 and 79 nM, respectively)

EGFR/HER2/DHFR-IN-3 (compound 4c) serves as an efficacious dual inhibitor specifically targeting EGFR/HER2, exhibiting IC50 values of 0.138 μM for EGFR and 0.092 μM for HER2, respectively. Moreover, it demonstrates inhibition of DHFR with an IC50 of 0.193 μM. Notably, this compound induces cell cycle arrest in the S phase and triggers apoptosis in MCF7 breast cancer cells [1].

EGFR/CDK2-IN-4 (compound 4c) is a dual inhibitor targeting EGFR and CDK-2, demonstrating IC50 values of 89.6 nM for EGFR and 165.4 nM for CDK-2. It prompts apoptosis in MCF-7 cells and causes S phase cell cycle arrest, exhibiting substantial anti-cancer activity with an IC50 of 2.74 μM against MCF-7 cells [1].

EGFR/CDK2-IN-3 (compound 4b) serves as a dual inhibitor targeting both EGFR and CDK-2, exhibiting IC50 values of 71.7 nM and 113.7 nM, respectively. It prompts apoptosis in MCF-7 cells and halts the cell cycle in the S phase while demonstrating substantial anti-cancer cell toxicity, inhibiting MCF-7 cells with an IC50 of 3.16 μM [1].

EGFR/HER2-IN-5 is an irreversible, orally active dual inhibitor of EGFR activity (IC50: 0.6 nM). EGFR/HER2-IN-4 shows potent EGFR kinase inhibitory activity against L858R and T790M mutations. EGFR/HER2-IN-4 exhibits significant anti-tumour effects in vivo and can be used to study lung cancer.

EGFR/HER2-IN-6 (compound 43) is a dual EGFR/HER2 and DHFR inhibitor with potent activity against EGFR kinase, HER2 kinase, and DHFR, characterized by IC50 values of 0.122 μM, 0.078 μM, and 0.585 μM, respectively. This compound displays notable anticancer properties in various cancer cell lines, while demonstrating a favorable safety profile and selectivity indices. Consequently, EGFR/HER2-IN-6 holds promise as a valuable tool in cancer research [1].

EGFR/HER2-IN-8 (compound 34) is an inhibitor of EGFR/HER2 and DHFR with IC50 values of 0.45, 0.244 and 5.669 μM for EGFR, HER2 and DHFR, respectively. EGFR/HER2-IN-8 can be used in the cancer research that exhibits anticancer activity against several cancer cell lines with high safety profile and selectivity indices [1].

EGFR/CDK2-IN-1, an inhibitor of both EGFR and CDK2, demonstrates effective cytotoxicity towards MCF7 and HepG2 cells, suggesting its potential application in cancer research.

EGFR/HER2-IN-9, a compound inhibiting both EGFR and HER2, demonstrates potency with IC50 values of 3.2 nM for EGFR, 14 nM for HER2, and 8.3 nM against the EGFR T790M mutation.

EGFR/HER2/CDK9-IN-3 (Compound 10) is a potent inhibitor of EGFR (IC50:191.08 nM), HER2 (IC50:132.65 nM), and CDK9 (IC50:113.98 nM). EGFR/HER2/CDK9-IN-3 showed significant anti-tumor effects.

EGFR/HER2-IN-7 is a highly selective and potent anticancer compound specifically designed to target MCF-7 breast cancer cells. It functions as a dual inhibitor, targeting both EGFR/HER2 kinases and DHFR (dihydrofolate reductase). Its inhibitory activities are measured with IC50 values of 0.18 μM for EGFR, 0.146 μM for HER2, and 0.907 μM for DHFR [1].

EGFR/HER2-IN-3 (Compound ZINC21942954) is a dual EGFR and HER2 inhibitor.

EGFR/HER2-IN-4 is an irreversible, orally active dual inhibitor of EGFR activity (IC50: 0.6 nM). EGFR/HER2-IN-4 shows potent EGFR kinase inhibitory activity against L858R and T790M mutations. EGFR/HER2-IN-4 exhibits significant anti-tumour effects in vivo and can be used to study lung cancer.

EGFR/HER2/TS-IN-1 are EGFR, HER2 and TS (Thymidylate synthase) inhibitors with IC50 values of 0.203, 0.088 and 0.168 μM, respectively, and have the ability to induce apoptosis (MCF7 cell death).

EGFR/HER2/DHFR-IN-1 is a highly selective and potent anticancer compound specifically targeting MCF-7 breast cancer cells. It acts as a multi-inhibitor, targeting the EGFR/HER2 kinase and DHFR enzymes, with IC50 values of 0.153 μM, 0.108 μM, and 0.291 μM, respectively. Its mechanism of action involves cell cycle arrest at the G1/S phase and induction of apoptosis in cells [1].

EGFR/HER2/CDK9-IN-1 (Compound 4) is a potent EGFR/HER2/CDK9 inhibitor with IC50 values of 90.17, 131.39 and 67.04 nM. EGFR/HER2/CDK9-IN-1 exhibits significant anti-tumour effects.

Erlotinib (NSC-718781) is an EGFR inhibitor (IC50: 2 nM). It is used for the treatment of non-small cell lung cancer.

Tyrphostin 8(4-Hydroxybenzylidenemalononitrile) is a potent GTPase inhibitor that inhibits EGFR kinase with an IC50 of 560 μM.Tyrphostin 8 inhibits protein serine/threonine calmodulin phosphatases (IC50=21 μM), enhances transferrin receptor-mediated transcytosis in Caco-2 cells, and increases the hypoglycemic effect of oral insulin-transferrin. hypoglycemic effect.

Nitroaspirin (NCX 4016) is a nitric oxide donor and a nitro-derivative of Aspirin, which combines with Nitroaspirin to inhibit cyclooxygenase. Nitroaspirin induces significant induction of cell cycle arrest and apoptosis in Cisplatin-resistant human ovarian cancer cells via down-regulation of EGFR/PI3K/STAT3 signaling and modulation of Bcl-2 family proteins. Nitroaspirin has antithrombotic and antiplatelet properties and acts as a direct and irreversible inhibitor of COX-1.

(-)-Epigallocatechin Gallate (EGCG) is an antioxidant polyphenol flavonoid that inhibits telomerase and DNA methyltransferase. (-)-Epigallocatechin Gallate (EGCG) blocks the activation of EGF receptors and HER-2 receptors. (-)-Epigallocatechin Gallate (EGCG) is a phenolic antioxidant found in a number of plants such as green and black tea. It inhibits cellular oxidation and prevents free radical damage to cells.

Erlotinib-13C6 (CP-358774-13C6) is a 13C-labeled Erlotinib. Erlotinib is a directly acting EGFR tyrosine kinase inhibitor, with an IC50 of 2 nM for human EGFR[1]. Erlotinib reduces EGFR autophosphorylation in intact tumor cells with an IC50 of 20 nM. Erlotinib is used for the treatment of non-small cell lung cancer[1].Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process[2]. [1]. Moyer JD, et al. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. 1997, 57(21), 4838-4848.[2]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.

AAA is an antagonist of G protein-coupled receptor 75 (GPR75).1It increases basal GPR75 protein levels and inhibits 20-HETE-induced reductions in GPR75 protein levels in PC3 cells. AAA (5 and 10 μM) also reduces 20-HETE-induced phosphorylation of EGFR, NF-κB, and Akt in, and cell migration of, PC3 cells.In vivo, AAA (10 mg/kg per day) reduces systolic blood pressure, albuminuria, renal angiotensin II levels, and cardiac hypertrophy in a Cyp1a1-Ren-2 transgenic rat model of malignant hypertension when administered prior to induction or after establishment of hypertension.2 1.Cárdenas, S., Colombero, C., Panelo, L., et al.GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cellsBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(2)158573(2020) 2.Sedláková, L., Kikerlová, S., Husková, Z., et al.20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic ratsBiosci. Rep.38(5)BSR20171496(2018)

Compound 5K (Multi-target kinase inhibitor 2) is a multi-targeted kinase inhibitor demonstrating activity against EGFR, Her2, VEGFR2, and CDK2 with IC50 values between 40 to 204 nM. It exhibits cytotoxic effects on HepG2, HeLa, MDA-MB-231, and MCF-7 cell lines, with IC50 values of 41, 57, 51, and 59 μM, respectively. Additionally, it induces cell cycle arrest and apoptosis specifically in HepG2 cells.

Pericosine A is a fungal metabolite that has been found inP. byssoidesand has anticancer activity.1It inhibits the growth of a variety of cancer cells, including breast, colon, lung, ovary, stomach, and prostate cell lines (GI50s = 0.05-24.55 μM) and increases survival in a P388 mouse xenograft model when administered at a dose of 25 mg/kg. Pericosine A inhibits EGFR by 40 to 70% when used at a concentration of 100 μg/ml. It also reacts with organosulfur compounds in skunk spray to form stable thioethers as odorless products.2 1.Yamada, T., Iritani, M., Ohishi, H., et al.Pericosines, antitumour metabolites from the sea hare-derived fungus Periconia byssoides. Structures and biological activitiesOrg. Biomol. Chem.5(24)3979-3986(2007) 2.Du, L., Munteanu, C., King, J.B., et al.An electrophilic natural product provides a safe and robust odor neutralization approach to counteract malodorous organosulfur metabolites encountered in skunk sprayJ. Nat. Prod.82(7)1989-1999(2019)

Taspine shows antitumor activity by modulating the EGFR signaling pathway of Erk1/2 and Akt in vitro and in vivo, it can inhibit growth and induce apoptosis of HUVEC in a dose-dependent manner, it has shown meaningful angiogenesis activity. Taspine exhibi

ZD-4190 is a compound that inhibits both the vascular endothelial growth factor receptor 2 (VEGFR2) and the epidermal growth factor receptor (EGFR) signaling pathways, utilized in cancer treatment.

EGFR-IN-78 (compound A5), a 2-aminopyrimidine derivative, serves as a reversible EGFR C797S-TK inhibitor and an apoptosis inducer. It exhibits anti-proliferative properties, impedes EGFR phosphorylation, and induces G2/M phase cell cycle arrest [1].

Zalutumumab, a fully human IgG1 monoclonal antibody, exhibits high affinity for the epidermal growth factor receptor (EGFR), selectively targeting its domain III. It functions by inhibiting the binding of the epidermal growth factor (EGF) and obstructing the receptor's active conformation through steric hindrance. With EC50 values of 7 nM for its IgG and 19 nM for the Fab fragment, Zalutumumab demonstrates potent interaction capabilities. This compound is primarily utilized in cancer research [1] [2] [3].

4-Chloro-6,7-bis(2-methoxyethoxy)quinazoline is a building block and synthetic intermediate.1,2,3,4,5It has been used as a precursor in the synthesis of receptor tyrosine kinase (RTK) inhibitors, dual RTK and histone deacetylase (HDAC) inhibitors, and anticancer compounds.1,2,3It is also a synthetic intermediate in the synthesis of EGFR inhibitors, including erlotinib , with antiproliferative activity.4,5

1. Furanodienone has effects on MCF-7 cells are mediated, at least in part, by inhibiting ERα signaling. 2. Furanodienone inhibits EGFR/HER2 signaling pathway in BT474 and SKBR3 cells, the effect is specifically dependent on the expression of HER2 but not EGFR .

Gefitinib hydrochloride (ZD1839 hydrochloride) is a potent and orally active EGFR tyrosine kinase inhibitor (EGFR-TKI) (IC 50 = 33 nM) that selectively inhibits EGF-stimulated tumor cell growth (IC 50 = 54 nM) and that blocks EGF-stimulated EGFR autophosphorylation in tumor cells. Gefitinib hydrochloride also induces autophagy, which has antitumour activity [1] [2].

Intetumumab (CNTO 95), a glycoengineered anti-EGFR monoclonal antibody designed for improved antibody-dependent cellular cytotoxicity (ADCC), is utilized in cancer research [1] [2].

AEE788 (NVP-AEE 788) has been used in trials studying the treatment of Cancer, Glioblastoma Multiforme, and Brain and Central Nervous System Tumors.

JBJ-09-063 hydrochloride is an EGFR inhibitor selective for mutants, demonstrating IC50 values of 0.147 nM, 0.063 nM, 0.083 nM, and 0.396 nM against EGFR L858R, EGFR L858R/T790M, EGFR L858R/T790M/C797S, and EGFR L747S, respectively. It effectively inhibits EGFR, Akt, and ERK1/2 phosphorylation, showing efficacy in both EGFR tyrosine kinase inhibitor (TKI)-sensitive and -resistant models. This compound holds potential for research on EGFR-mutant lung cancer.

VEGFR-2-IN-30, a compound acting primarily as a VEGFR-2 inhibitor (IC50: 66 nM), demonstrates additional inhibitory effects on PDGFR, EGFR, and FGFR1, with IC50 values of 180, 98, and 82 nM, respectively. It effectively arrests cancer cells in the S-phase and induces both early and late apoptosis.

JBJ-09-063 TFA is a mutant-selective allosteric EGFR inhibitor, displaying IC50 values of 0.147 nM for EGFR L858R, 0.063 nM for EGFR L858R/T790M, 0.083 nM for EGFR L858R/T790M/C797S, and 0.396 nM for EGFR L747S mutations. It effectively reduces phosphorylation of EGFR, Akt, and ERK1/2, demonstrating efficacy in models sensitive and resistant to EGFR tyrosine kinase inhibitors (TKI). JBJ-09-063 TFA holds potential for research in EGFR-mutant lung cancer [1].

pan-HER-IN-2 (Compound C6) is an orally active, reversible, broad-spectrum HER inhibitor that acts on EGFR (IC50: 0.72 nM), HER4 (IC50: 2.0 nM), EGFRT790M (IC50: 8.2 nM), and L858R (IC50: 75.1 nM). pan-HER-IN-2 induces apoptosis and has anti-tumour effects.

EGFR-IN-16 (AG473) is an inhibitor of EGFR in human A431 cells.