egfr (cell: h1975)

Olmutinib (HM61713, BI 1482694) is an orally available small molecule, a mutant-selective inhibitor of epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Olmutinib binds to and inhibits mutant forms of EGFR, thereby leading to cell death of EGFR-expressing tumor cells. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit the EGFR wild-type form.

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

WK88-1, an inhibitor of Hsp90, effectively induces the degradation of various oncogenic signaling molecules, including EGFR, ErbB2, and ErbB3, in the gefitinib-resistant H1975 cell line. This leads to subsequent growth arrest and apoptosis.

EGFR-IN-139 (compound PD 18) is an EGFR inhibitor with IC50 values of 12.88 nM (wild type), 10.84 nM (L858R T790M), and 42.68 nM (L858R T790M C797S). It demonstrates significant anticancer activity against the A549 and H1975 cancer cell lines, which express high levels of EGFR. EGFR-IN-139 exhibits strong selectivity for cancer cells and can be utilized in research on non-small cell lung cancer (NSCLC).

EGFR-IN-55 is a potent inhibitor of EGFR, acting on EGFRWT (IC50: 70 nM) and EGFRL858R T790M (IC50: 3.9 nM). EGFR-IN-55 was able to block the cell cycle of NCI-H1975 cells in G0 G1 phase, exhibiting anticancer effects.

EGFR-IN-60 is an effective, orally active, safe antitumor agent. EGFR-IN-60 significantly inhibits EGFRWT (IC50: 83 nM), EGFRT790M (IC50: 26 nM), EGFRL858R (IC50: 53 nM) and JAK3 (IC50: 69 nM). IN-60 inhibited H1975 cells carrying the EGFRT790M mutation (IC50: 1.32 μM) and A431 cells overexpressing EGFRWT (IC50: 4.96 μM). EGFR-IN-60 increased the Bax Bcl-2 ratio, which induced apoptosis induction and cell death.

EGFR-IN-62 is a potent inhibitor of EGFR kinase with IC50 values of 10 nM for L858R T790 M, 29 nM for WT and 2 42 nM for L858R T790 M C797S. EGFR-IN-62 blocks the cell cycle of A549 and or H1975 cells in G1 G0 phase and induces apoptosis and motility inhibition. EGFR-IN-62 effectively inhibited the proliferation of A549 (IC50: 2.53 μM) and H1975 cells (IC50: 1.56 μM).

EGFR-IN-61 (compound 22a), a potent EGFR kinase inhibitor, exhibits IC50 values of 42 nM for L858R T790M, 137 nM for L858R T790M C797S, and 743 nM for WT. Additionally, it demonstrates antiproliferative activity against the A549 and H1975 cell lines, with IC50 values of 2.14 μM and 1.82 μM, respectively [1].

PROTAC EGFR degrader 4 is a potent molecule designed to target and degrade mutant EGFR, effectively inducing degradation of EGFR del19 and EGFR L858R T790M with DC50 values of 0.51 nM and 126 nM, respectively. It significantly inhibits the growth of HCC827 and H1975 cell lines, demonstrating IC50 values of 0.83 nM and 203.1 nM, respectively. The induced degradation of EGFR by this compound is associated with autophagy [1].

PROTAC EGFR degrader 7 (compound 13b) is a potent and selective CRBN-recruiting agent targeting EGFR L858R T790M mutations with a DC50 of 13.2 nM. It effectively inhibits proliferation in NCI-H1975 cells with an IC50 of 46.82 nM and significantly induces apoptosis and G2 M phase arrest in these cells. Demonstrating antitumor efficacy, PROTAC EGFR degrader 7 holds promise for non-small cell lung cancer (NSCLC) research [1].

PROTAC EGFR degrader 8 (T-184) is a PROTAC that selectively degrades the epidermal growth factor receptor (EGFR) with a DC50 of 15.56 nM in HCC827 cells, and inhibits the growth of cell lines H1975, PC-9, and HCC827 with IC50 values of 7.72 nM, 121.9 nM, and 14.21 nM, respectively. This compound is used primarily for cancer research, particularly in the context of non-small cell lung cancer (NSCLC) [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].

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].

ALK EGFR-IN-3 is a dual ALK and EGFR inhibitor demonstrating potent anti-proliferative effects on various cancer cell lines, including H1975, PC9, and Baf3-EML4-ALK, with IC50 values of 0.1360, 0.0332, and 0.0339 μM [1].

PROTAC EGFR degrader 7 (compound 13b) is a potent, selective, CRBN-recruiting EGFRL858R T790M degrader with a DC50 of 13.2 nM. It effectively inhibits NCI-H1975 cell proliferation with an IC50 of 46.82 nM, induces apoptosis, and causes G2 M phase arrest. This compound shows antitumor activity and is applicable in non-small cell lung cancer (NSCLC) research.

EGFR-IN-90 (compound 34), an orally active EGFR inhibitor, demonstrates potent activity against EGFRL858R T790M C797S with an IC50 of 5.1 nM and effectively inhibits the proliferation of the H1975-TM cell line carrying EGFRL858R T790M C797S mutations with an IC50 of 0.05 μM. Additionally, EGFR-IN-90 suppresses tumor growth in the H1975-TM xenograft tumor model [1].

Flavokawain 1i, a derivative of chalcones flavokawain A, flavokawain B, and flavokawain C, exhibits anticancer and antiviral properties. At a concentration of 30 µM, it suppresses the growth of gefitinib-resistant H1975 non-small cell lung cancer (NSCLC) cells by 36% and modulates the protein expression by reducing the levels of heat shock protein 90 (Hsp90) client proteins, including EGFR, c-Met, HER2, Akt, and cyclin-dependent kinase 4 (Cdk4), while increasing the levels of Hsp70, indicative of Hsp90 inhibition. Additionally, intramuscular injection of flavokawain 1i lowers viral loads in pigs afflicted with porcine reproductive and respiratory syndrome virus (PRRSV).