t790m

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.

Alflutinib (Firmonertinib) is an inhibitor of EGFR, and its targets including EGFR activating mutations and T790M, thus leading to tumor growth inhibition.

Alflutinib mesylate (AST2818 mesylate) ,is an irreversible tyrosine kinase inhibitor that selectively inhibits EGFR mutations, especially T790M.

EGFRT790M/L858R-IN-9 (Compound 8) is an inhibitor targeting the EGFR-L858R/T790M mutations. It effectively inhibits the phosphorylation of the EGFR-L858R/T790M mutant kinase, demonstrating an IC50 value of 0.0064 µM. Additionally, EGFRT790M/L858R-IN-9 can suppress the proliferation of non-small cell lung cancer (NSCLC) cells, making it useful for cancer research.

EGFRT790M/L858R-IN-3 (compound B1) is an EGFRL858R/T790M inhibitor with an IC50 value of 13 nM. In H1975 cells, EGFRT790M/L858R-IN-3 demonstrates antitumor activity with an IC50 of 0.087 μΜ. Additionally, it inhibits cell migration in A549 cells and induces apoptosis in H1975 cells (cellapoptosis).

EGFRWT/T790M/L858R-IN-1 (compound 10d) is a potent inhibitor of EGFR, demonstrating IC50 values of 0.097, 0.280, and 0.051 μM for EGFRWT, EGFRT790M, and EGFRL858R, respectively. This compound can be utilized in cancer research.

EGFRWT/T790M-IN-1 (Compound 16h) is a dual inhibitor targeting both EGFRWT and EGFRT790M. It can arrest the cell cycle at the G2/M phase and induce apoptosis. Additionally, EGFRWT/T790M-IN-1 exhibits anticancer activity.

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.

EGFRT790M/VEGFR-2-IN-1 (Compound 6) is a dual inhibitor targeting the EGFRT790M mutant (IC50=0.26 μM) and VEGFR-2 (IC50=0.95 μM). It effectively blocks tumor cell proliferation and angiogenesis signaling pathways. This compound exhibits potent cytotoxicity against various cancer cell lines (HCT116, MCF-7, HepG2, A549; IC50=5.35-9.90 μM) and holds potential for research in non-small cell lung cancer and solid tumors.

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].

EGFR T790M/L858R-IN-4, a potent inhibitor of EGFR T790M/L858R with anticancer properties (WO2024064091A1; Example 14) [1].

EGFR T790M/L858R-IN-5 (example 52) functions as a potent EGFR T790M/L858R inhibitor, demonstrating a 92.9% inhibition rate at a concentration of 0.05 μM [1].

EGFR T790M/L858R-IN-6 (compound 53), classified as a pyrimidine compound, serves as an effective inhibitor of EGFR T790M/L858R, demonstrating 90.88% inhibition of enzyme activity at a concentration of 0.05 μM [1].

EGFR T790M/L858R-IN-7 (Compound 72), a novel pyrimidine compound, exhibits high efficacy in inhibiting the EGFR T790M and L858R mutations, with a 93% inhibition rate at 0.05 μM. It achieves its inhibitory action by specifically binding to the kinase domain of EGFR, which prevents phosphorylation activity [1].

EGFRT790M/L858R-IN-8 (compound 9) is a potent inhibitor of EGFR, specifically targeting the EGFRT790M/L858R mutations with an IC50 of 56.8 μM. This compound does not show significant antiproliferative effects on cancer cell lines A549, A431, and NHI-H1975.

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.

Wighteone (Erythrinin B) is a small molecule compound derived from Genista ephedroides with potential antifungal and anticancer activity against EGFR L858R/T790M mutant non-small cell lung cancer.

BI-4020 is a fourth-generation, orally active, and non-covalent inhibitor of EGFR tyrosine kinase. It exhibits activity against the triple mutant EGFR del19 T790M C797S variant (IC50=0.2 nM in BaF3 cell lines), the double mutant EGFR del19 T790M and primary mutant EGFR del19 (IC50=1 nM), and EGFR wt (IC50=190 nM). BI-4020 also shows high kinome selectivity and good DMPK properties.

CHMFL-EGFR-202 is a potent, irreversible inhibitor of EGFR mutant kinase with IC50 values of 5.3 nM for drug-resistant mutant EGFR T790M and 8.3 nM for WT EGFR kinases.

DBPR112 is an orally active furanopyrimidine-based EGFR inhibitor with IC50s of 15 nM for EGFRWT and 48 nM for EGFRL858R/T790M, capable of occupying the ATP-binding site and demonstrating significant antitumor efficacy.

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.

EGFR-IN-9 is a potent EGFR kinase inhibitor with IC50s of 7 nM, 28 nM for the wild type EGFR kinase and double mutant EGFR kinase (L858R/T790M). EGFR-IN-9 has antitumor activity.

EGFR-IN-87 is a potent EGFR tyrosine kinase inhibitor with anticancer activity that inhibits EGFR_d746-750, EGFR_L858R/T790M, and EGFR_WT in A431 cells, and can be used for cancer research.