1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemED8-MMAECat. No.: HY-15162ACAS No.: 2070009-72-0Synonyms: D8-Monomethyl auristatin E分式: CHDNO分量: 726.03作靶點(diǎn): Microtubule/Tubulin; ADC Cytotoxin作通路: Cell Cycle/DNA Damage; Cytoskeleton; Antibody-drugConjugate/ADC Related儲(chǔ)存式: 4C, st

2、ored under nitrogen* 該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)現(xiàn)配，即刻使。溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 40 mg/mL (55.09 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.3774 mL 6.8868 mL 13.7735 mL5 mM 0.2755 mL 1.3774 mL 2.7547 mL10 mM 0.1377 mL 0.6887 mL 1.3774 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液；該

3、產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)現(xiàn)配，即刻使。BIOLOGICAL ACTIVITY物活性 D8-MMAE是氘代標(biāo)記的有絲分裂抑制劑MMAE。IC50 & Target Microtubule 1體外研究Antibody-drug conjugates (ADC) comprise targeting antibodies armed with potent small-molecule payloads.1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEADCs are generated to target different receptor

4、s on the anaplastic large cell lymphoma line L-82, butdelivered the same cytotoxic payload (monomethyl auristatin E, MMAE), and the intracellular concentration ofreleased MMAE correlated with in vitro ADC-mediated cytotoxicity independent of target expression ordrug:antibody ratios. LC-MS is used to

5、 measure the concentration of MMAE in a parallel cohort of L-82tumors with an identical treatment regimen. Although tumor volume is not different among treatment groups 3days after dose, the intratumoral MMAE measurement reveals two patterns. First, intratumoral MMAEconcentration increases proportio

6、nally to the ADC dose, which correspondes to stronger antitumor activity.Second, the intratumoral MMAE concentration obtained from treatment with both cOKT9-vcMMAE andcAC10-vcMMAE is similar at each dose, consistent with the observation that tumor responded similarly tothese two ADCs 1.體內(nèi)研究 Intratum

7、oral MMAE concentrations consistently correlates with the extent of tumor growth inhibition in tumorxenograft models. IHC analysis reveals that nonbinding control-treated tumors consist of both CD30+ andCD30-cells, presumably because they do not kill either CD30+ or CD30- Karpas 299 cells. Only CD30

8、- cellsare found in cAC10-vcMMAF-treated tumors, illustrating that cAC10-vcMMAF eliminates most CD30+ cells.Interestingly, the two tumors that relapses from cAC10-vcMMAE treatment are also found to be CD30- by theend of study, indicating a small fraction of CD30- cells might have escaped from bystan

9、der killing in thesetwo remaining tumors 1.PROTOCOLKinase Assay 1 Cell pellets are collected 24 hours after ADC treatment. Cell count, diameter, and circularity are determinedon Vi-Cell Counter. MMAE extraction and quantification method is performed. Briefly, tumors or cell pelletsare homogenized wi

10、th methanol and acetonitrile containing internal standard (d8-MMAE for MMAE detectionand 13C-MMAF for MMAF detection). The homogenates are centrifuged at 10,000 rpm to precipitate proteinand protein-bound payloads. The supernatant is then subjected to solid phase extraction, and signals ofMMAE and M

11、MAF are detected by LC-MS 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Drug Metab Dispos. 2017 Nov;45(11):1120-1132.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Li F, et al. Intracellular Released Payload Influences Potency and Bystander-Killing Effects of Antibody-Drug Conjugates in PreclinicalModels. Cancer Res. 2016 May 1;76(9):2710-9.McePdfHeightCaution: Product h