egfr-t790m

Oritinib (SH-1028) is an inhibitor of EGFR with IC50s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM for EGFR (wt), EGFR (L858R), EGFR (L861Q), EGFR (L858R/T790M), EGFR (d746-750), EGFR (d746-750/T790M), respectively. Oritinib can be used in studies about the treatment of non-small cell lung cancer.

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.

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-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-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-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-3 is an irreversible, covalent inhibitor of EGFRWT and EGFRT790M with IC50 values of 28.1 nM and 24.6 nM, respectively. It also inhibits tubulin polymerization, exhibiting an IC50 of 5.1 μM. EGFRWT/T790M-IN-3 demonstrates significant antiproliferative effects on HCT116 and T47D cells, with IC50 values of 3.12 μM and 4.12 μM, respectively. This compound is applicable in research pertaining to cancers such as non-small cell lung cancer, colon cancer, and breast cancer.

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.

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.

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.

AV-412 (MP412) is an EGFR inhibitor for EGFR, EGFR T790M, EGFR L858R, EGFR L858R/T790M, and ErbB2, with IC50 values of 0.75, 0.79, 0.5, 2.3, and 19 nM, respectively.

Mutated EGFR-IN-2 is an inhibitor of mutant-selective EGFR.

Rociletinib hydrobromide is an orally delivered inhibitor of the mutant form of EGFR kinase (Kis: 21.5 nM and 303.3 nM for EGFR L858R/T790M and EGFR WT).

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.

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.