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).

EGFRm+（PC9）和EGFRm+/ T790M（H1975）肿瘤模型肿瘤中,口服 AZD9291（5 mg/kg）能够抑制AKT和ERK信号通路及体内的EGFR磷酸化,引起肿瘤的消退

在突变EGFR细胞系中,AZD9291能够有效得抑制细胞增殖。

ACY-1215 is dissolved and subsequently diluted in assay buffer [50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, and 20 μM tris(2-carboxyethyl)phosphine] to 6-fold the final concentration. HDAC enzymes are diluted to 1.5-fold of the final concentration in assay buffer and pre-incubated with ACY-1215 for 10 minutes before the addition of the substrate. The amount of FTS (HDAC1, HDAC2, HDAC3, and HDAC6) or MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8, and HDAC9) used for each enzyme is equal to the Michaelis constant (Km), as determined by a titration curve. FTS or MAZ-1675 is diluted in assay buffer to 6-fold the final concentration with 0.3 μM sequencing grade trypsin. The substrate/trypsin mix is added to the enzyme/compound mix and the plate is shaken for 60 seconds and then placed into a SpectraMax M5 microtiter plate reader. The enzymatic reaction is monitored for release of 7-amino-4-methoxy-coumarin over 30 minutes, after deacetylation of the lysine side chain in the peptide substrate, and the linear rate of the reaction is calculated[1].

AZD-9291 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1]. PC-9 cells are seeded into T75 flasks (5×105 cells/flask) in RPMI growth media and incubated at 37°C, 5% CO2. The following day the media is replaced with media supplemented with a concentration of EGFR inhibitor equal to the EC50 concentration predetermined in PC-9 cells. Media changes are carried out every 2-3 days and resistant clones allowed to grow to 80% confluency prior to the cells being trypsinised and reseeded at the original seeding density in media containing twice the concentration of EGFR inhibitor. Dose escalations are continued until a final concentration of 1.5 μM Gefitinib, 1.5 μM Afatinib, 1.5 μM WZ4002 or 160 nM AZD-9291 are achieved[1].

1421373-65-0

C28H33N7O2

499.61

AZD-9291;Mereletinib;奥希替尼;Osimertinib

[1]Zhang F, Wang W, Long Y, et al. Characterization of drug responses of mini patient-derived xenografts in mice for predicting cancer patient clinical therapeutic response[J]. Cancer Communications. 2018, 38(1): 1-12. [2]Cross, et al. Mol Cancer Ther. 2013, 12, A109. [3]Patent. 2013, WO20132014448 A1.

[1]Liu Y, Lai M, Li S, et al. LS‐106, a novel EGFR inhibitor targeting C797S, exhibits anti‐tumor activities both in vitro and in vivo. Cancer Science. 2021 [2]Mancini M, Thomas Q D, Bourdel S, et al. Generation and Characterization of a New Preclinical Mouse Model of EGFR-Driven Lung Cancer with MET-Induced Osimertinib Resistance. Cancers. 2021, 13(14): 3441 [3]Yu J, Zhang L, Peng J, et al. Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways. Biochemical pharmacology. 2022, 195: 114864. [4]Shang J, Ning S, Chen Y, et al. MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer. Acta Pharmacologica Sinica. 2021, 42(1): 120-131

Ethanol:22 mg/mL(44 mM)
DMSO:92 mg/mL (184.1 mM)
H2O:<1 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years