egfr tki

Larotinib is an orally active, potent, and broad-spectrum tyrosine kinase inhibitor (TKI) with an IC50 of 0.6 nM for EGFR.

ONO-7475 is an inhibitor with high specificity for anexelekto and MER tyrosine kinase

EGFR-IN-8, a dual inhibitor targeting both EGFR and c-Met, shows potential as a promising candidate for further development in treating EGFR TKI-resistant NSCLC.

Rezivertinib (BPI-7711) is an orally active, highly selective, and irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) with potent activity against both common activation EGFR and resistance T790M mutations. Additionally, Rezivertinib demonstrates excellent central nervous system (CNS) penetration and exhibits antitumor activity [1][2].

Gefitinib hydrochloride (ZD1839 hydrochloride) is a potent and orally active EGFR tyrosine kinase inhibitor (EGFR-TKI) (IC 50 = 33 nM) that selectively inhibits EGF-stimulated tumor cell growth (IC 50 = 54 nM) and blocks EGF-stimulated EGFR autophosphorylation in tumor cells. Additionally, it induces autophagy, demonstrating antitumor activity [1] [2].

Transtinib is an effective and irreversible EGFR tyrosine kinase inhibitor (EGFR-TKI) that is active against L858R/T790M mutated NSCLC cell lines and xenografts.

Lazertinib (GNS-1480) is an effective, highly mutant-selective and irreversible EGFR-TKI with IC50 values of 1.7 nM, 2 nM, 5 nM, 20.6 nM and 76 nM for Del19 T790M, L858R T790M, Del19, L85R and Wild type EGFR respectively.

Mavelertinib (PF-06747775) is an orally available, selective and potent EGFR tyrosine kinase (EGFR TKI) inhibitor with inhibitory effects on T790M/L858R and T790M/Del, and can be used in the study of oncology and respiratory diseases.

EGFR-IN-23, identified as compound 8 in WO2021244502A1, is a potent EGFR tyrosine kinase inhibitor (TKI) demonstrating an inhibitory concentration (IC50) of 8.05 nM against the BaF3/EGFR-DEL19/T790M/C797S cell line.

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.

ASK120067 is a potent and orally active inhibitor of EGFRT790M (IC50:0.3 nM) with selectivity over EGFRWT (IC50:6.0 nM). ASK120067 is a third-generation EGFR-TKI for the research of non-small cell lung cancer (NSCLC)[1]. In the in vitro kinase assay ASK120067 potently inhibits the EGFR L858R T790M and EGFR T790M resistant mutants with IC50 values of 0.3 nM and 0.5 nM, respectively, as well as the EGFRexon19del sensitizing mutant (IC50= 0.5 nM). The 50 of ASK120067 against wild-type EGFR (EGFRWT) is 6 nM[1].ASK120067 selectively inhibits the growth of EGFR-mutant cell lines and exhibits potent antiproliferative activity in the mutant EGFR NSCLC cells, with IC50 values of 12 nM, 6 nM and 2 nM against NCI-H1975 (T790M mutation), PC-9, and HCC827 cells (sensitizing mutations), respectively. However, it shows moderate or weak anti-growth activities in A431, LoVo and A549 cells (EGFRWT), with IC50 values ranging from 338 nM to 1541 nM[1].ASK120067 (0.1-100 nM) inhibits the phosphorylation of EGFR at Tyrosine residue 1068 and its downstream signaling proteins AKT and ERK in NCI-H1975 cells (EGFRL858R T790M) even at low dosage (0.1-1 nM). Additionally, ASK120067 inhibits p-EGFR and p-Akt and p-erk in EGFR WT A431 cell until the concentration reaches 10 to 100 nM[1]. ASK120067 (oral gavage; 5-20 mg kg; once daily; 21 days) results in significantly regressed tumor growth, with a tumor growth inhibition (TGI) rate of 85.7%, and administration of 10 mg kg ASK120067 causes dramatic tumor shrinkage with a TGI rate of 99.3%, exhibiting a similar potency with Osimertinib[1]. [1]. Tao Zhang, et al. Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance. Mol Cancer. 2020 May 13;19(1):90.

ARI-1 is a receptor tyrosine kinase-like orphan receptor 1 (ROR1) inhibitor that binds to ROR1's extracellular Frizzled domain, effectively inhibiting aberrant ROR1 expression linked to non-small cell lung cancer (NSCLC) and EGFR-TKI-induced drug resistance. It modulates PI3K/AKT/mTOR signaling pathways in a ROR1-dependent manner and demonstrates potent inhibition of NSCLC cell proliferation and migration, exhibiting antitumor activity in vivo [1].

Epitinib is an orally active, selective, blood-brain barrier crossing epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).

Larotinib mesylate hydrate is a potent, broad-spectrum, and orally active tyrosine kinase inhibitor (TKI), primarily targeting EGFR with an IC50 value of 0.6 nM.

JBJ-09-063 is a mutant-selective allosteric inhibitor of the epidermal growth factor receptor (EGFR), with potent inhibitory activity demonstrated by half-maximal inhibitory concentrations (IC50s) of 0.147 nM for EGFR L858R, 0.063 nM for EGFR L858R T790M, 0.083 nM for EGFR L858R T790M C797S, and 0.396 nM for EGFR L747S. This compound effectively decreases phosphorylation of EGFR, Akt, and ERK1 2, showing efficacy in both EGFR tyrosine kinase inhibitor (TKI)-sensitive and resistant models. JBJ-09-063 holds potential for research into EGFR-mutant lung cancer.

Dovitinib Dilactic Acid (Dovitinib (TKI-258) Dilactic Acid) is the Dilactic acid of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3 c-Kit) with IC50 of 1 nM 2 nM, also potent to class IV (FGFR1 3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGFR1 and HER2. Phase 4.

JBJ-09-063 hydrochloride is an EGFR inhibitor selective for mutants, demonstrating IC50 values of 0.147 nM, 0.063 nM, 0.083 nM, and 0.396 nM against EGFR L858R, EGFR L858R/T790M, EGFR L858R/T790M/C797S, and EGFR L747S, respectively. It effectively inhibits EGFR, Akt, and ERK1/2 phosphorylation, showing efficacy in both EGFR tyrosine kinase inhibitor (TKI)-sensitive and -resistant models. This compound holds potential for research on EGFR-mutant lung cancer.

JBJ-09-063 TFA is a mutant-selective allosteric EGFR inhibitor with IC50 values of 0.147 nM for EGFR L858R, 0.063 nM for EGFR L858R T790M, 0.083 nM for EGFR L858R T790M C797S, and 0.396 nM for EGFR L747S mutations. It effectively reduces phosphorylation of EGFR, Akt, and ERK1 2, demonstrating efficacy in models both sensitive and resistant to EGFR tyrosine kinase inhibitors (TKI). JBJ-09-063 TFA holds potential for research in EGFR-mutant lung cancer [1].

HX103, an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-based fluorogenic probe, exhibits selective inhibition towards various EGFR mutations, including EGFR 19 del, EGFR L858R, EGFR wild type, and EGFR T790M, with respective IC50 values of 1.3, 1.5, 4.0, and 977 nM. It is utilized for quantifying active-EGFR to foresee agent sensitivity in NSCLC (non-small cell lung cancer) patients harboring EGFR-activating mutations [1].