l858r

Almonertinib (HS-10296) is an inhibitor specifically targeting EGFR activation mutations and the resistant EGFR T790M mutation, exhibiting limited activity against wild-type EGFR.

Almonertinib hydrochloride (HS-10296 hydrochloride) is a small molecule inhibitor of EGFR-activating mutations and T790M-resistant mutation with limited activity against wild-type EGFR.

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.

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.

Gefitinib (ZD1839) is an EGFR first-generation inhibitor with oral activity that inhibits the EGFR 19 Del and L858R mutations. Gefitinib has antitumor activity and is used for the treatment of EGFR-mutated non-small-cell lung cancers. Gefitinib administration RESULTS in the development of the EGFR C797S resistance mutation.

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.

Saracatinib (AZD0530) (AZD0530) is an effective Src inhibitor (IC50: 2.7 nM), and effective to Lck, Fyn, Lyn, Blk, Fgr and c-Yes.

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.

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.

MS 154 is a potent and selective cereblon-recruiting Degrader (PROTAC®) of mutant epidermal growth factor receptor (EGFR), comprising a cereblon-binding moiety joined by a linker to gefitinib(Iressa). MS 154 decreases EGFR protein levels, inhibits downstream signaling in and inhibits proliferation of mutant EGFR-bearing lung cancer cells (DC50values are 11 and 25 nM in HCC-827 and H3255 cells, respectively; Dmax> 95% at 50 nM), but not in WT-EGFR-bearing ovarian and lung cancer cells lines. Bioavailable in mice following ip administration.

MS 39 is a highly effective, highly affinity and selective depressant of mutant epidermal growth factor receptor (EGFR) with high efficiency, high affinity and selectivity. MS 39, conjured by gefitinib to VHL ligand via a linker, effectively induced the degradation of mutant EGFR (DC50 values in HCC827(exon 19 del) and H3255 (L858R mutation) lung cancer cell lines were 5 nM and 3.3 nM, respectively). However, there was no significant effect in wild-type EGFR cell lines with concentrations up to 10 μM. MS 39 inhibited the proliferation of H3255 lung cancer cells in vitro and was bioavailable in mice after administration.

MS 154N is a negative control for MS 154. The compound exhibits high binding-affinity for WT and L858R-mutant EGFR (Kdvalues are 3 and 4.3 nM, respectively), but does not significantly induce degradation of EGFR mutants.

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

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.

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.