h1975 egfr

PF-06459988 is a novel, effective, orally active, irreversible, and selective epidermal growth factor receptor (EGFR) mutant inhibitor. PF-06459988 has high efficiency and high affinity for EGFRs double mutants containing T790M, and has minimal activity against WT EGFR. PF-06459988 makes a candidate drug for the treatment of cancer.

Osimertinib (AZD-9291) is an EGFR third-generation inhibitor that inhibits the T790M resistance mutation produced by second-generation EGFR inhibitors with irreversible and oral activity. Osimertinib has antitumor activity for the treatment of EGFR-mutated non-small-cell lung cancer.

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.

OTUB1 USP8-IN-1 is a potent OTUB1 USP8 inhibitor with potential anticancer activity, demonstrating IC50 values of 0.17 nM for OTUB1 and 0.28 nM for USP8. OTUB1 USP8-IN-1 can be used in the study of non-small-cell lung cancer.

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

Afatinib Dimaleate (BIBW 2992MA2) is an orally bioavailable anilino-quinazoline derivative and inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with antineoplastic activity.

Afatinib (BIBW 2992) is an irreversible inhibitor of the EGFR family (EGFR-wt, EGFR-L858R, EGFR-L858R T790M, and HER2) with IC50s of 0.5 nM, 0.4 nM, 10 nM, and 14 nM, respectively.

Osimertinib mesylate (AZD-9291 mesylate) is an EGFR third-generation inhibitor that inhibits the T790M resistance mutation produced by second-generation EGFR inhibitors with irreversible and oral activity. Osimertinib mesylate has antitumor activity for the treatment of EGFR-mutated non-small-cell lung cancer.

Zipalertinib (TAS6417, CLN-081) is a novel, highly potent, orally active covalent EGFR tyrosine kinase inhibitor that uniquely binds to the ATP binding site of the EGFR hinge region with an IC50 value of 1.1-8.0 nM.

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.

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.

NS-062 is an orally effective, irreversible covalent inhibitor targeting EGFR, demonstrating antiproliferative activity in the resistant double mutant H1975 cells with an IC50 of 0.19 μM. It also exhibits antitumor activity in a murine H1975 xenograft model.

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).

PF-6274484, a high affinity, irreversible covalent inhibitor of EGFR kinase with Ki of 0.14 nM, inhibits the autophosphorylation of wild-type EGFR in A549 cells and EGFRL858R T790M in H1975 cells with IC50 of 5.8 nM and 6.6 nM, respectively.

Limertinib (ASK120067) is an orally active and highly efficient epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR T790M. Limertinib can be used for studying non-small cell lung cancer.

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).

WZ8040 is a novel mutant-selective irreversible EGFRT790M inhibitor, does not inhibit ERBB2 phosphorylation (T798I).

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.

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 3, a highly potent molecule, exhibits remarkable cellular activity against H1975 and HCC827 cells, maintaining high selectivity. It additionally reveals the lysosome's crucial role in the degradation mechanism of mutant EGFR [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].