osimertinib

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.

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.

Osimertinib mesylate (AZD-9291 mesylate) is an EGFR third-generation inhibitor that inhibits the T790M resistance mutation produced by second-generation EGFR inhibitors with irreversible and oral activity. Osimertinib mesylate has antitumor activity for the treatment of EGFR-mutated non-small-cell lung cancer.

Osimertinib-d6 is a deuterated compound of Osimertinib. Osimertinib has a CAS number of 1421373-65-0. Osimertinib is a small molecule tyrosine kinase receptor inhibitor and antineoplastic agent that is used in the therapy of selected forms of advanced non-small cell lung cancer (NSCLC).

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

Dosimertinib-d3 is a potent, orally active inhibitor of EGFR, known to reduce the expression of p-EGFR and p-ERK proteins, thereby exhibiting antiproliferative and anti-tumor effects. It holds promise for research into non-small-cell lung cancer (NSCLC).

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

DBPR112 is a potent EGFR inhibitor (IC50=487 nM) as a Clinical Candidate for the Treatment of Non-Small Cell Lung Cancer. DBPR112), DBPR112 not only displayed a potent inhibitory activity against EGFRL858R/T790M double mutations but also exhibited tenfold potency better than the third-generation inhibitor, osimertinib,against EGFR and HER2 exon 20 insertion mutations. Overall, pharmacokinetic improvement through lead-to-candidate optimization yielded fourfold oral AUC better that afatinib along with F = 41.5%, an encouraging safety profile, and significant antitumor efficacy in in vivo xenograft models.

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.

HJM-561 is a potent and selective EGFR PROTAC with oral bioavailability, capable of overcoming osimertinib-resistant EGFR triple mutations and demonstrating anti-tumor activity [1].

Rezivertinib analogue 1, a process impurity of osimertinib mesylate, serves as a research tool in the study of non-small cell lung cancer (NSCLC) [1].

Olmutinib is a novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor, used in the treatment of T790M mutation positive non-small cell lung cancer. Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. EGFRs are frequently over-expressed in lung cancer and contribute to activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways which both promote cell survival and proliferation. By inhibiting EGFR activation, Olmutinib attenuates the activation of these tumor-promoting pathways. In the first phase I/II clinical study of Osimertinib, 800 mg/ day was chosen as the dose for subsequent studies, and the dose-limiting toxicity and maximum tolerated dose was not reached. Olmutinib received breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.

Becotatug (JMT-101) is an IgG1 antibody targeting EGFR, which can be conjugated to Afatinib and Osimertinib, serving as a synthetic antibody-drug conjugate (ADC) [1].