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.

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

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.

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-2 (Compound ZINC35560729) is a dual inhibitor targeting 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.

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 ).

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].

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/CDK2-IN-2 (compound 6a) is a dual inhibitor targeting EGFR and CDK-2, with IC50 values of 19.6 nM and 87.9 nM, respectively. It induces apoptosis in MCF-7 cells and arrests cell cycle progression in the S phase, demonstrating notable anticancer activity with an IC50 of 0.39 μM [1].

EGFR/HER2/DHFR-IN-2 (Compound 4b) is an inhibitor of EGFR, HER2, and DHFR, with IC50 values of 0.248, 0.156, and 0.138 μM, respectively, and 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; it also reduces the growth of breast cancer tumors [1].

EGFR mutant-IN-2 (Compound D51) is an inhibitor of EGFR mutants, specifically targeting EGFR L858R T790M C797S and EGFR del19 T790M C797S mutants with IC50 values of 14 nM and 62 nM, respectively. This compound exhibits favorable pharmacokinetic (PK) parameters, safety properties, in vivo stability, and demonstrates antitumor activity [1].

EGFR c-Met-IN-2 (Compound H-22) is a dual inhibitor of EGFR c-Met that arrests the G2 M phase to inhibit cell proliferation and demonstrates antitumor 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].

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

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 that inhibits cyclooxygenase. It induces cell cycle arrest and apoptosis in Cisplatin-resistant human ovarian cancer cells by down-regulating EGFR/PI3K/STAT3 signaling and modulating Bcl-2 family proteins. Additionally, Nitroaspirin possesses antithrombotic and antiplatelet properties and acts as a direct and irreversible inhibitor of COX-1.

Gefitinib is an EGFR tyrosine kinase inhibitor, with IC50 of 2-37 nM in NR6wtEGFR cells. Gefitinib D8 is a deuterium labeled Gefitinib.