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DM4

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Chemical Structure| 796073-69-3 同义名 : Maytansinoid DM 4
CAS号 : 796073-69-3
货号 : A348562
分子式 : C38H54ClN3O10S
纯度 : 99%+
分子量 : 780.367
MDL号 : MFCD28144516
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(134.55 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Tubulin normally undergoes a cycle of detyrosination/tyrosination on the carboxy terminus of its alpha-subunit and this results in subpopulations of tyrosinated tubulin and detyrosinated tubulin[1]. Maytansinoid DM4 is a thiol-containing maytansine derivative with highly potent cytotoxicity. Maytansinoid DM4 is a tubulin inhibitor, inhibits the assembly of microtubules by binding to tubulin, with a linker structure can create an antibody-drug conjugate (ADC). Maytansine is a natural benzoansamacrolide product isolated from the bark of the African shrub Maytenus ovatus. Maytansine binds to the same site on tubulin as the vinca alkaloids, with similar in vitro inhibition constants, but is a more-potent cytotoxin[2]. Maytansinoid DM1 and DM4 inactivated CYP3A from human liver microsomes with K(i)/k(inact) values of 4. 8 ± 0. 9 μM/0. 035 ± 0. 002 min(-1) and 3. 3 ± 0. 2 μM/0. 114 ± 0. 002 min(-1), respectively. DM1 and DM4 inactivated recombinant CYP3A4 with K(i)/k(inact) values of 3. 4 ± 1. 0 μM/0. 058 ± 0. 005 min(-1) and 1. 4 ± 0. 3 μM/0. 117 ± 0. 006 min(-1), respectively[3]. Although S-methyl-DM1 and S-methyl-DM4 inhibited polymerization more weakly than maytansine, at 100 nmol/L they suppressed dynamic instability more strongly than maytansine (by 84% and 73%, respectively, compared with 45% for maytansine). Both maytansine and S-methyl-DM1 bound to tubulin with similar K(D) values (0. 86 ± 0. 2 and 0. 93 ± 0. 2 μmol/L, respectively)[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.28mL

0.26mL

0.13mL

6.41mL

1.28mL

0.64mL

12.81mL

2.56mL

1.28mL
参考文献

[1] L Lafanechère, D Job. The third tubulin pool. Neurochem Res. 2000 Jan;25(1):11-8.

[2] Beck A, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017 May;16(5):315-337.

[3] John A Davis 1, Dan A Rock, et al. In vitro characterization of the drug-drug interaction potential of catabolites of antibody-maytansinoid conjugates. Drug Metab Dispos. 2012 Oct;40(10):1927-34.

[4] Manu Lopus, Emin Oroudjev,et al. Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules. Mol Cancer Ther. 2010 Oct;9(10):2689-99.