Mutant EGFR inhibitor is a selective and potent Mutated EGFR inhibitor, inhibits L858R activating mutant, the Exonl9 deletion activating mutant and the T790M resistance mutant.

Sunvozertinib (DZD9008) is a potent ErbBs and BTK inhibitor and has inhibitory effects on EGFR, Her2 and mutant epidermal growth factor. Sunvozertinib showed inhibition of EGFR exon 20 NPH insertion, EGFR exon 20 ASV insertion, EGFR L858R and T790M mutation, and Her2 exon 20 YVMA and EGFR WT A431. IC50 were 20.4, 20.4, 1.1, 7.5 and 80.4 nM, respectively.

BI-4020 is a fourth-generation, orally active, and non-covalent inhibitor of EGFR tyrosine kinase. BI-4020 exhibits activity agains 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 exhibits high kinome selectivity and good DMPK properties.

EGFR-IN-1 hydrochloride is an irreversible and specific inhibitor of L858R/T790M mutant EGFR with 100-fold selectivity over wild-type EGFR. EGFR-IN-1 hydrochloride exhibits potent antitumor and antiproliferative activity in H1975 cells and the 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.

CHMFL-EGFR-202 is a potent, irreversible inhibitor of EGFR mutant kinase (IC50s: 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases).

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 mesylate (Mereletinib mesylate) is an irreversible and mutant selective EGFR inhibitor (IC50s: 12/1 nM for EGFR(L858R) and EGFR(L858R/T790M)).

YS-363 is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor (EGFR), exhibiting half-maximal inhibitory concentrations (IC50) of 0.96 nM for the wild-type EGFR and 0.67 nM for the L858R mutant variant. This compound has been shown to induce G0/G1 cell cycle arrest and apoptosis in targeted cells [1].

Theliatinib, a potent and highly selective EGFR inhibitor, with anti-tumor activity. Ki of 0.05 nM for wild type EGFR, and IC50s of 3 and 22 nM for EGFR and EGFR T790M/L858R mutant, respectively.

BEBT-109 is a potent selective inhibitor of pan-mutant EGFR with enhanced pharmacokinetic properties, suitable for research on various mutant-EGFR-driven non-small cell lung cancer (NSCLC) [1].

Avitinib (AC0010), also known as AC0010 or AC0010MA, is an orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, avitinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the drug-resistant T790M EGFR mutant, which prevents signaling mediated by mutant forms of EGFR. This may both induce cell death and inhibit tumor growth in EGFR-mutated tumor cells. EGFR, a receptor tyrosine kinase that is mutated in a variety of Ys, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors, which also inhibit wild-type EGFR.

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

WSD0922-FU is a blood-brain-barrier (BBB) penetrable selective inhibitor of epidermal growth factor receptor (EGFR) and various EGFR mutations, including but not limited to the EGFR variant III (EGFRvIII) mutant form, with potential antineoplastic activity. WSD0922-FU is able to penetrate the BBB and specifically targets, binds to and inhibits EGFR and specific EGFR mutations, which prevents EGFR/EGFR mutant-mediated signaling and leads to cell death in EGFR/EGFR mutant-expressing tumor cells. Compared to other EGFR inhibitors that are not able to penetrate the BBB, WSD0922-FU may have therapeutic benefits in brain tumors, such as glioblastoma (GBM) and metastatic CNS tumors.

EGFR-IN-22 is a highly effective inhibitor targeting wild type EGFR and its mutant form, EGFR L858R/T790M/C797S, displaying IC50 values of 4.91 nM and 0.54 nM, respectively.

Selective EGFR Degrader. Comprises the EGFR inhibitor lapatinib (Cat. No. 6811) joined by a linker to a von Hippel-Lindau (VHL) recruiting ligand. Exhibits selectivity for EGFR, including mutant forms, over HER2. Induces degradation of EGFR in OVCAR8 cells.

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.

TNO155 is a protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; src homology region 2 domain phosphatase; PTPN11) inhibitor(IC50 : 0.011 µM),with potential antineoplastic activity.

Naquotinib mesylate (ASP8273 (mesylate)) is an orally available, mutant-selective and irreversible inhibitor of EGFR(iC50s of 8-33 nM and 230 nM for toward EGFR mutants and EGFR).

EGFR-IN-36 is a potent inhibitor of EGFR, capable of acting on EGFR (WT) (IC50: 19.09 nM), HER2 (WT) (IC50: 120.01 nM), HER2 (A775_G776insYVMA) (IC50: 2.35 nM). EGFR-IN-36 exhibits the potential to study wild and/or mutant EGFR and/or HER2 kinase-mediated tumors.

(Rac)-JBJ-04-125-02 (JBJ-04-125-02) is effective as a single agent in both in vitro and in vivo models of EGFR-mutant lung cancer.

EGFR-IN-11 is a selective inhibitor of EGFR-tyrosine kinase and induces cell apoptosis. EGFR-IN-11 inhibits triple mutant EGFRL858R/T790M/C797S with an IC50 of 18 nM and arrests cell cycle at G0/G1.

JBJ-09-063 TFA is a mutant-selective allosteric EGFR inhibitor, displaying 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 sensitive and resistant to EGFR tyrosine kinase inhibitors (TKI). JBJ-09-063 TFA holds potential for research in EGFR-mutant lung cancer [1].

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.

EAI001 is a potent and selective mutant epidermal growth factor receptor (EGFR) variant inhibitor that inhibits EGFRL858R/T790M with an IC50 value of 24 nM.EAI001 can be used in cancer research.

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

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.

Nazartinib (EGF816) (EGF816, NVS-816) is a covalent, irreversible, mutant-selective EGFR inhibitor that has nanomolar inhibitory potency against activating mt (L858R, ex19del) and T790M mt, with up to 60-fold selectivity over wild type (wt) EGFR in vitro.

MTI-31 (LXI-15029) is a potent, orally active and highly selective inhibitor of mTORC1 and mTORC2. MTI-31 is selective for mTOR (Kd: 0.20 nM) versus PIK3CA, PIK3CB and PIK3G with >5,000 fold selectivity in mTOR binding assays. MTI-31 shows an IC50 of 39 nM for mTOR in LANCE assay of mTOR substrate phosphorylation with 100 μM ATP[1].

Zorifertinib (AZD3759) is an orally active, effective and central nervous system-penetrant EGFR inhibitor. The IC50 values were 0.2, 0.3 and 0.2 nM for EGFR L858R mutant, TK wild-type, and Exon 19Del enzymes, respectively.

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.

(3S, 4S)-PF-06459988 is the less active S enantiomer of PF-06459988, which is a potent irreversible inhibitor of T790M mutant epidermal growth factor receptor (EGFR). PF-06459988 exhibits excellent selectivity against EGFR wild-type due to its minimally reactive electrophile, which reduces the likelihood of off-target labeling.

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).

CNX-2006 is a novel irreversible mutant-selective EGFR inhibitor with IC50 of < 20 nM, with very weak inhibition at wild-type EGFR.

WZ3146 is a mutant-selective irreversible inhibitor of EGFR(L858R) and EGFR(E746_A750) with IC50 of 2 nM and 2 nM; does not inhibit ERBB2 phosphorylation (T798I).

WZ4002 is a mutant-selective EGFR inhibitor for EGFR(L858R) and EGFR(T790M) with IC50 of 2 nM/8 nM.

YK-029A, an orally active EGFR mutant inhibitor, targets both EGFR T790M and EGFRex20ins mutations. It demonstrates notable antitumor efficacy, inducing tumor regression in EGFRex20ins-driven patient-derived xenograft (PDX) models [1].

EGFR-IN-89 (compound 13k) is a fourth-generation inhibitor selectively targeting EGFR mutations, exhibiting potent activity with an IC50 of 10.1 nM against Del19/T790M/C797S mutations, and demonstrating greater selectivity for mutant forms over wild type [1].

Lifirafenib (Beigene-283) is a potent inhibitor of RAF family kinases and EGFR in biochemical assays with IC50 of 23, 29 and 495 nM for the recombinant BRAFV600E kinase domain, EGFR and EGFR T790M/L858R mutant respectively.

EMI1 can be used in the mutant EGFR-associated, drug-resistant non-small-cell lung cancer(NSCLC) research. EMI1 is an inhibitor of EGFR L858R/T790M/C797S and EGFR ex19del/T790M/C797S [1].

EGFR-IN-18 is a potent inhibitor of the enzymatic activity of the L858R/T790M/C797S mutant EGFR (4.9 nM) and is also able to reduce the enzymatic activity of wild-type EGFR (47 nM).

Olafertinib (RX-518) is a novel mutant-selective, irreversible, orally available EGFR inhibitor. It can overcome T790M-mediated resistance in NSCLC.

Osimertinib dimesylate is an irreversible and mutant selective EGFR inhibitor (IC50s: 12 and 1 nM against EGFR L858R and EGFR L858R/T790M).

Naquotinib (ASP8273) (ASP8273) is an orally available, mutant-selective and irreversible EGFR inhibitor; (IC50s: 8-33 nM and 230 nM toward EGFR mutants and EGFR.

HKB99 is a mutant inhibitor of phosphoglycerate mutase 1 (PGAM1), which inhibits the growth and metastasis of non-small cell lung cancer.HKB99 acts synergistically with EGFR inhibitors and assists in the killing of tumors by EGFR inhibitors.HKB99 promotes oxidative stress, which induces alterations in a variety of signaling pathways.HKB99 can be used in the study of metabolism-related diseases.HKB99 can be used in the study of metabolism-related diseases.HKB99 can be used in the study of metabolism-related diseases.

Theliatinib (Xiliertinib) tartrate is a potent and highly selective EGFR inhibitor, displaying ATP-competitive and orally active properties. It exhibits promising efficacy with a K_i of 0.05 nM and an IC_50 of 3 nM for EGFR, alongside a specific IC_50 of 22 nM against the EGFR T790M/L858R mutant. Notably, Theliatinib demonstrates over 50-fold selectivity for EGFR compared to other kinases, underscoring its targeted action in inhibiting EGFR.

BAY 2476568 is a selective and potent EGFR inhibitor that acts on both wild-type EGFR (IC50 <0.2 nM) and mutant EGFR (IC50 <0.2 nM).

JBJ-09-063 is a mutant-selective allosteric inhibitor of the epidermal growth factor receptor (EGFR), exhibiting potent inhibitory activity with 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, demonstrating efficacy in both EGFR tyrosine kinase inhibitor (TKI)-sensitive and resistant models. JBJ-09-063 holds potential for research into EGFR-mutant lung cancer.

JBJ-04-125-02 can inhibit cancer cell proliferation and EGFRL858R/T790M/C797S signaling. JBJ-04-125-02 has anti-tumor activities. JBJ-04-125-02 is a potent, mutant-selective, allosteric and orally active EGFR inhibitor with an IC50 of 0.26 nM for EGFRL858

HER2-IN-6 is a potent inhibitor of HER2. HER2-IN-6 has the potential to be investigated in wild and/or mutant EGFR and/or HER2 kinase-mediated tumors.