35846-53-8 Usage
Description
Maitansine is an organic heterotetracyclic compound and a 19-membered macrocyclic lactam antibiotic. It is originally isolated from the Ethiopian shrub Maytenus serrata but can also be found in other Maytenus species. Maitansine exhibits cytotoxicity against many tumor cell lines and has shown potential in prolonging the survival of mice bearing certain types of leukemia.
Uses
Used in Antineoplastic Applications:
Maitansine is used as an antineoplastic agent for its cytotoxic effects on various tumor cell lines. In low doses, it has been shown to prolong the survival of mice bearing vincristine-sensitive P388 leukemia. In vitro, it suppressed the growth of U21 0, LSl78Y, and P388 leukemia cells, indicating its potential in targeting cancer cells. Additionally, maitansine has been found to inhibit DNA formation by P388 cells to a greater extent than RNA and protein synthesis, suggesting its mechanism of action in disrupting cancer cell replication.
Used in Pharmaceutical Research:
Maitansine is used as a research compound for studying its potential applications in cancer treatment. Its unique structure and cytotoxic properties make it a valuable tool for understanding the mechanisms of cancer cell growth and the development of novel therapeutic strategies.
Biological Functions
Maytansine is a potent microtubule-targeted compound that inhibits proliferation of cells at mitosis. Antibody-maytansinoid conjugates consisting of maytansinoids (DM1 and DM4) attached to tumor-specific antibodies have shown promising clinical results The microtubule-targeting maytansinoids accumulate in cells and induce mitotic arrest at 250- to 1000-fold lower concentrations than those required for their association with tubulin or microtubules.
Toxicology
Maytansine, an ansa macrolide isolated from African plants of the genera Maytenus and Putterlickia was first described almost two decades ago. It had been reported to be active against several forms of cancer, but a later phase II evaluation suggested no major role for this drug in tumor treatment. Although the toxic side effects were moderate, the antitumor activity was also not impressive.Maytansine binds to tubulin rapidly and reversibly. Competitive inhibition of binding between maytansine and the vinca alkaloids has been observed, suggesting that maytansine must occupy at least one of vinblastine's binding sites on the tubulin molecule. The number of the maytansine binding sites is not known. Assembly of MT is inhibited at maytansine concentrations below 1μM. This suggests a substoichiometric poisoning mechanism as in the cases of colchicine, vinblastine and podophyllotoxin, but the details are not known. In contrast to many other MT-interacting toxins，maytansine does not promote the formation of aberrant tubulin polymers, even at millimolar concentrations. In fact, low concentrations of maytansine even inhibit vinblastine-induced formation of aberrant polymers.
Mode of action
Maytansine is a new drug undergoing clinical investigation. It has functional similarities to vincristine.Maytansine, an ansa macrolide of considerable antitumor potency, is obtained from plants of the genera Maytenus and Putterlickia. Maytansine binds rapidly and reversibly to tubulin, and is a competitive inhibitor of vinca alkaloid binding. Colchicine has no effect on maytansine binding. Maytansine and the vinca alkaloids have comparable binding constants, share a common binding site, although an additional site or attachment position specific for maytansine appears to be present. Maytansine may inhibit tubulin polymerization by interfering with certain critical-SH groups necessary for assembly. Like the vincas, it inhibits assembly substroichiometric. Unlike the vincas, as well as colchicine and podophyllotoxin, maytansine appears capable of inducing rapid microtubule disassembly in vitro when added to microtubules at end state. Furthermore, maytansine enhances alkylation by iodoacetamide，an effect opposite to that obtained with V BL, suggesting that maytansine may have different conformation effects on tubulin.
References
Walpert-Defillipes et al., Biochem. Pharmacol., 24, 751 (1975)
Check Digit Verification of cas no
The CAS Registry Mumber 35846-53-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,5,8,4 and 6 respectively; the second part has 2 digits, 5 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 35846-53:
(7*3)+(6*5)+(5*8)+(4*4)+(3*6)+(2*5)+(1*3)=138
138 % 10 = 8
So 35846-53-8 is a valid CAS Registry Number.
InChI:InChI=1/C34H46ClN3O10/c1-18-11-10-12-26(45-9)34(43)17-25(46-32(42)36-34)19(2)30-33(5,48-30)27(47-31(41)20(3)37(6)21(4)39)16-28(40)38(7)23-14-22(13-18)15-24(44-8)29(23)35/h10-12,14-15,19-20,25-27,30,43H,13,16-17H2,1-9H3,(H,36,42)/b12-10+,18-11+/t19-,20+,25+,26-,27+,30+,33+,34+/m1/s1
