egfr in 1

EGFR-IN-1, an orally active and irreversible selective inhibitor targeting L858R T790M mutant EGFR, exhibits strong antiproliferative and antitumor activity, particularly against H1975 cells and first line mutant HCC827 cells. This compound potently inhibits Gefitinib-resistant EGFR L858R T790M mutations with a 100-fold selectivity over the wild-type EGFR.

EGFR-IN-1 hydrochloride is an irreversible and specific inhibitor of L858R T790M mutant EGFR, with 100-fold selectivity over wild-type EGFR. It exhibits potent antitumor and antiproliferative activity in H1975 cells and mutant HCC827 cells with IC50s of 4 and 28 nM, respectively.

Mutated EGFR-IN-1 (Osimertinib analog) is a valuable intermediate in designing inhibitors for mutated EGFR, including L858R EGFR, Exon19 deletion activating mutant, and T790M resistance mutant.

EGFR mutant- in-1, A 5-methylpyrimidopyridone derivative are effective selective EGFRL858R T790M C797S mutant inhibitors with IC50 of 27.5 nM, which significantly weakened EGFRWT effect.

EGFR PI3Kα-IN-1 (compound 30k), a dual EGFR PI3Kα inhibitor, exhibits potent activity with IC 50 values of 3.6 nM (EGFRL858R T790M) and 30 nM (PI3Kα). It effectively inhibits tumor cell proliferation and demonstrates significant anticancer activity.

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.

LSD1 EGFR-IN-1 (compound L-1) is an effective inhibitor of LSD1, EGFRT790M L858R, and EGFRL858R T790M C797S, with IC50 values of 6.24, 2.06, and 5.01 μM, respectively. This compound plays a significant role in cancer research.

Dual Galectin-3 EGFR-IN-1 (Compound 29) is a dual inhibitor targeting Galectin-3 and EGFR, with dissociation constants (KD) of 52.29 μM and 3.31 μM, respectively. It inhibits TGF-β-induced hepatic stellate cell (HSC) activation, induces apoptosis in LX-2 cells, and shows antifibrotic activity in the liver.

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.

TrxR EGFR-IN-1 (Compound L1Au2) is a TrxR EGFR inhibitor with activity against both gefitinib-sensitive and -resistant lung cancer, effectively suppressing tumor proliferation and promoting apoptosis. It enhances GPX4 degradation through autophagosome-lysosome and proteasome pathways, leading to ferroptosis. Additionally, it induces endoplasmic reticulum stress and triggers immunogenic cell death, making it applicable for studies on gefitinib-resistant lung cancer.

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

EGFR BRAFV600E-IN-1 (Compound 23) is a potent dual inhibitor of EGFR (IC50: 0.08 μM) and BRAFV600E (IC50: 0.15 μM), exhibiting anti-proliferative effects on A-549 (IC50: 1.2 μM), MCF-7 (IC50: 0.79 μM), Panc-1 (IC50: 1.3 μM), and HT-29 (IC50: 1.23 μM).

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

EGFR BRAF-IN-1, a 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivative, is a potent inhibitor of EGFR BRAF, inhibiting BRAFV600E (IC50:45 nM) and cancer cell proliferation (GI50=35 nM), with good antioxidant effect.

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 C797S-IN-1 is a potent inhibitor targeting the EGFR-C797S mutation, with an IC50 value of 0.128 µM, exhibiting significant anti-proliferative and anti-tumor effects by inhibiting p-EGFR expression in a dose-dependent manner.

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 CSC-IN-1 is a dual inhibitor of the epidermal growth factor receptor (EGFR [IC50 10.52 nM]) and cancer stem cells (CSC), potentially applicable in triple-negative breast cancer research.

EGFR-IN-1 TFA is an orally active and irreversible L858R T790M mutant selective EGFR inhibitor. EGFR-IN-1 TFA potently inhibits Gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR . EGFR-IN-1 TFA displays strong antiproliferative activity against the H1975 cells and the first line mutant HCC827 cells. Antitumor activity [1] .

ALK EGFR-IN-1 (Compound 8l) is a dual inhibitor targeting both ALK and EGFR, effectively blocking their phosphorylation. It demonstrates potent inhibition of ALK EGFR mutants with IC50 values of 4.3 nM for EGFR L858R T790M in H1975 cells and 3.6 nM for EML4-ALK in BaF3 cells. This compound may be applicable in the research of non-small cell lung cancer (NSCLC) [1].

EGFR AURKB-IN-1 (compound 7) serves as a dual inhibitor targeting EGFR AURKB, effectively inhibiting the phosphorylations of L858R EGFR and AURKB with IC50 values of 0.07 and 1.1, respectively. The compound engages with the hydrophobic region I or the αC-helix out pocket of EGFR and the back pocket of AURKB. This binding action suppresses tumor cell growth, division, and metastasis, making it a valuable agent for cancer research [1].

EGFR microtubule-IN-1 (Compound 10c) functions as a dual inhibitor of both EGFR and tubulin, displaying an IC 50 of 10.66 nM against EGFR. It effectively reduces the phosphorylation levels of EGFR, AKT, and ERK, impedes tubulin polymerization, and induces apoptosis [1].

GLUT1 EGFR-IN-1 (compound H) is a potent inhibitor of both GLUT1 and EGFR. It targets the ATP-binding site of the EGFR tyrosine kinase and inhibits GLUT1-mediated energy metabolism, resulting in reduced ATP, MMP, intracellular lactate, and nuclear translocation of EGFR. GLUT1 EGFR-IN-1 is applicable in the research of nasopharyngeal carcinoma (NPC) and triple-negative breast cancer (TNBC).

EGFR Akt-IN-1 (compound 17) serves as an effective inhibitor of EGFR Akt, exhibiting IC50 values of 12.89 μM and 10.88 μM in A549 cells, respectively. This compound induces cell cycle arrest at the S phase.