마이탄신

그림문자(GHS)

• 그림문자(GHS)

  

• 신호 어

  Danger

• 유해·위험 문구

  H331：흡입하면 유독함

• 예방조치문구

  P261：분진·흄·가스·미스트·증기·...·스프레이의 흡입을 피하시오.

  P262：눈, 피부, 의복에 묻지 않도록 하시오.

  P264：취급 후에는 손을 철저히 씻으시오.

  P264：취급 후에는 손을 철저히 씻으시오.

  P270：이 제품을 사용할 때에는 먹거나, 마시거나 흡연하지 마시오.

  P271：옥외 또는 환기가 잘 되는 곳에서만 취급하시오.

  P280：보호장갑/보호의/보안경/안면보호구를 착용하시오.

  P301+P310：삼켰다면 즉시 의료기관(의사)의 진찰을 받으시오.

  P302+P352：피부에 묻으면 다량의 물로 씻으시오.

  P304+P340：흡입하면 신선한 공기가 있는 곳으로 옮기고 호흡하기 쉬운 자세로 안정을 취하시오.

  P311：의료기관(의사)의 진찰을 받으시오.

  P321：(…) 처치를 하시오.

  P330：입을 씻어내시오.

  P403+P233：용기는 환기가 잘 되는 곳에 단단히 밀폐하여 저장하시오.

  P405：밀봉하여 저장하시오.

  P501：...에 내용물 / 용기를 폐기 하시오.

마이탄신 화학적 특성, 용도, 생산

• 개요

  This novel ansa macrolide alkaloid occurs in a number of May tan us species. The structure given has been elucidated from chemical and spectroscopic data. In low doses (25-50 mcg/kg), maytansine prolonged the survival of mice bearing vincristine-sensitive P388 leukemia but not those bearing vincristine-resistant tumour lines. In vitro, it suppressed the growth of U21 0, LSl78Y and P388 leukemia cells with ED₅₀ of 2 X 10^-9 , 1.5 X 10^-9 and 6 X 10^-10M respectively and elevated the mitotic index in L 121 0 cells. From labelling studies it was shown that the alkaloid inhibited DNA formation by P388 cells to a greater extent than RNA and protein synthesis. Maytensine did not inhibit RNA polymerase from Escherichia coli at levels as high as 1 X 10^-4M.

• 용도

  Antineoplastic.

• 정의

  ChEBI: An organic heterotetracyclic compound and 19-membered macrocyclic lactam antibiotic originally isolated from the Ethiopian shrub Maytenus serrata but also found in other Maytenus species. It exhibits cytotoxicity against many tumo r cell lines.

• 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.

• 참고 문헌

  Walpert-Defillipes et al., Biochem. Pharmacol., 24, 751 (1975)

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