EGFR IN 2

EGFR-IN-2 is a non-covalent, orally available and mutation-selective EGFR inhibitor for the treatment of non-small cell lung cancer (NSCLC), with high selectivity for resistant single and double mutant T790M with IC50 = 27 nm to 33 nM, and low inhibitory activity for wild-type H292 (IC50 = 218 nM).

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

SOS1/EGFR-IN-2 (Compound 4) functions as a dual inhibitor of SOS1 and EGFR, exhibiting IC50 values of 8.3 and 14.6 nM, respectively. It demonstrates significant antiproliferative effects on cancer cells harboring various KRAS mutations.

TopoisomeraseII/EGFR-IN-2 (Compound 3) is an inhibitor targeting Topoisomerase IIα, with an IC50 of 0.122 μM, and EGFR-TKWT, with an IC50 of 16.8 μM. It suppresses the proliferation of HeLa and HepG2 cells, induces cell cycle arrest, and triggers apoptosis. Additionally, it upregulates caspase-3 and Bax while downregulating Bcl-2, making it a potential agent for the study of liver and cervical cancers.

VEGFR-2/c-Met/EGFR-IN-2 is an inhibitor targeting VEGFR-2, c-Met, and EGFR, with IC50 values of 0.32 μM, 0.021 μM, and 9.3 μM, respectively. Known as c-Met-IN-27, this compound inhibits the proliferation of cancer cells and demonstrates anti-angiogenic activity in vivo by suppressing neovascularization in the chick embryo chorioallantoic membrane (CAM) assay. It is applicable in research related to breast and lung cancers.

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, with IC50s of 0.0034, 0.0065, and 0.0018 μM, respectively [1].

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

EGFR/ErbB-2/ErbB-4 inhibitor-2 (EGFR/ErbB2 Inhibitor) is a cell-permeable compound that inhibits EGFR and c-ErbB2 with IC50 values of 20 nM and 79 nM, respectively.

EGFR/VEGFR2-IN-1 (Compound 10e) serves as an inhibitor for VEGFR-2 and EGFR, with respective IC50 values of 0.26 and 0.14 μM. It inhibits microtubule protein polymerization with an IC50 of 40.9 μM and induces cell apoptosis (Apoptosis). EGFR/VEGFR2-IN-1 is applicable in research related to anti-leukemia and anti-lymphoma treatments.

EGFR/VEGFR2-IN-2 (compound 4b) serves as a dual inhibitor of VEGFR-2 and EGFR.

EGFR/VEGFR2-IN-3 (compound 9) is an effective inhibitor of EGFR and VEGFR-2, demonstrating IC50 values of 0.129 µM for EGFR, 0.142 µM for VEGFR-2, and 3.428 µM for COX-2. This compound exhibits cytotoxic properties and induces cell apoptosis (apoptosis) as well as cell cycle arrest at the G2/M phase.

EGFR/VEGFR2-IN-4 (Compound 19) is an irreversible inhibitor of both EGFR and VEGFR-2, exhibiting IC50 values of 18.7 nM and 102.3 nM, respectively, under conditions of 1 μM ATP.

EGFR/COX-2-IN-1 is an EGFR/COX-2 inhibitor that effectively targets EGFRWT, EGFRT790M, COX-1, and COX-2 with IC50 values of 0.12, 0.076, 20.1, and 1.52 μM, respectively. It inhibits MCF-7, HT-29, and A-549 cells with IC50 values of 1.20, 5.14, and 14.81 μM, respectively. The compound induces apoptosis by upregulating Bax protein and downregulating Bcl-2 protein levels. Additionally, EGFR/COX-2-IN-1 significantly increases the proportion of cells in the G2/M phase in MCF-7 cells, demonstrating a broad-spectrum antitumor effect.

EGFR/DHFR-IN-2 (9b) is a dual inhibitor of h-DHFR/EGFR TK, exhibiting IC50 values of 0.192 μM for h-DHFR and 0.109 μM for EGFR. It causes cell cycle arrest at the G1/S phase and induces apoptosis. Additionally, EGFR/DHFR-IN-2 (9b) is a potential inhibitor of CYP2C9 and CYP3A4. This compound can be utilized in cancer research.

EGFR/HER2-IN-17 (Compound 7h) is a dual inhibitor targeting the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2). This compound suppresses cancer cell proliferation by interacting with the binding pockets of EGFR and HER2, activating Caspase-3 and Caspase-8, and reducing the expression of Bcl-2, thus inducing apoptosis (apoptosis). EGFR/HER2-IN-17 holds potential for cancer research.

EGFR kinase inhibitor 2 (compound A-7) is a potent EGFR inhibitor targeting the mutations EGFRL858R/T790M/C797S and EGFRDel19/T790M/C797S. This compound shows potential in addressing acquired resistance in the treatment of non-small cell lung cancer.

EGFRWT/T790M-IN-2 (Compound 7c) is an inhibitor of EGFR T790M/WT with IC50 values of 0.08 and 0.13 μM, respectively. This compound induces apoptosis by arresting the cell cycle at the G0-G1 phase and demonstrates antitumor activity.

EGFR-PK/JNK-2-IN-1 (Compound 6c) is a dual inhibitor of EGFR-PK and JNK-2, with IC50 values of 2.7 and 3.0 μM, respectively. It can induce apoptosis and cause cell cycle arrest at various stages. This compound is applicable in cancer research.

EGFR-TK-IN-2 (compound 10b) is an EGFR-TK inhibitor with an IC50 value of 0.16 μM, and it suppresses cell proliferation.

EGFR/HER2-IN-19 (Compound L1) is a dual inhibitor targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). It holds potential for research into cancers driven by EGFR/HER2.

EGFR/COX-2-IN-3 is a highly selective dual-target inhibitor of EGFR and COX-2, with IC50 values of 0.098 μM and 0.05 μM for the two targets respectively. Pharmacological prediction Results: show that it possesses good oral bioavailability and blood-brain barrier penetration ability. Meanwhile, it exhibits significant analgesic effects and anti-glioblastoma pharmacological activity, and can be applied to mechanism and efficacy research of glioblastoma and other tumors.

EGFR/HDAC-IN-2 (Compound 38) is a dual inhibitor of EGFR and HDAC3, exhibiting IC50 values of 20.34 nM and 1.09 nM, respectively. This compound demonstrates exceptional antiproliferative activity against cancer cells, inhibiting cell migration and inducing late-stage apoptosis. In xenograft mouse models, EGFR/HDAC-IN-2 significantly suppresses the growth of triple-negative breast cancer (TNBC) tumors and is applicable in research on cancers such as TNBC.

EGFR/VEGFR2-IN-9 (Compound 9b) is an inhibitor of VEGFR-2 (IC50 = 1.325 μM) and EGFR (IC50 = 1.891 μM). It significantly suppresses the proliferation of various cancer cell lines, particularly leukemia cells. EGFR/VEGFR2-IN-9 increases the expression levels of Bax, caspase-3, and p53, while decreasing Bcl-2 expression. This compound induces apoptosis and causes cell cycle arrest at the G1 phase. It is suitable for research on anti-tumor angiogenesis and multidrug-resistant cancers.

EGFR/COX-2-IN-2 (Compound 10a) is a dual inhibitor targeting the epidermal growth factor receptor (EGFR) with an IC50 of 6.0 μM and cyclooxygenase-2 (COX-2) with an IC50 of 50 μM. It induces cell cycle arrest in the S phase and triggers apoptosis. EGFR/COX-2-IN-2 holds potential for research in cancer and inflammation-related diseases.