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MMAE-d8

Catalog No. T10948 CAS 2070009-72-0

Synonyms: D8-MMAE, D8-Monomethyl auristatin E

D8-MMAE (D8-Monomethyl auristatin E) is an effective mitotic inhibitor and tubulin inhibitor, deuterated MMAE.

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MMAE-d8, CAS 2070009-72-0

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Biological Description

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Storage & Solubility Information

Description	D8-MMAE (D8-Monomethyl auristatin E) is an effective mitotic inhibitor and tubulin inhibitor, deuterated MMAE.
In vitro	Antibody-drug conjugates (ADC) contain targeted antibodies with effective small molecule payloads. The ADC is produced against different receptors on the anaplastic large cell lymphoma L-82 line, but delivers the same cytotoxic payload (monomethyl auristatin E, MMAE). ADC-mediated cytotoxicity is not related to target expression or drug: antibody ratio. LC-MS was used to measure the concentration of MMAE in the L-82 tumor parallel cohort by the same treatment protocol. Although there was no difference in tumor volume between the treatment groups 3 days after administration, intratumoral MMAE measurements showed two patterns. First, the MMAE concentration in the tumor increases in proportion to the ADC dose, which corresponds to stronger antitumor activity. Second, intra-tumor MMAE concentrations obtained after treatment with cOKT9-vcMMAE and cAC10-vcMMAE were similar at each dose, which is consistent with the observation that tumors responded similarly to these two ADCs.
In vivo	In tumor xenograft models, the MMAE concentration in the tumor is always correlated with the degree of tumor growth inhibition. IHC analysis showed that tumors that were not combined with control treatment consisted of CD30 + and CD30 cells, presumably because they did not kill CD30 + or CD30- Karpas 299 cells. Only CD30-cells were found in tumors treated with cAC10-vcMMAF, indicating that cAC10-vcMMAF eliminated most CD30 + cells. Interestingly, at the end of the study, two tumors recurring from the treatment of cAC10-vcMMAE were also found to be CD30-, indicating that in the remaining two tumors, a small portion of CD30-cells may have escaped bystanders Kill.

Synonyms	D8-MMAE, D8-Monomethyl auristatin E
Molecular Weight	726.03
Formula	C39H59D8N5O7
CAS No.	2070009-72-0

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 100 mg/mL (137.74 mM), Sonication is recommended.

References and Literature

1. Li F, et al. Intracellular Released Payload Influences Potency and Bystander-Killing Effects of Antibody-Drug Conjugates in Preclinical Models. Cancer Res. 2016 May 1;76(9):2710-9.

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Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

MMAE-d8 2070009-72-0 Others MMAE-d-8 MMAE d8 D8-MMAE MMAEd8 D8-Monomethyl auristatin E inhibitor inhibit

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