Maitansin
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- CAS-Nr.
- 35846-53-8
- Bezeichnung:
- Maitansin
- Englisch Name:
- Maytansine
- Synonyma:
- NSC 153858;Maytansine;maitansine;Maitansina;Microtubule/Tubulin,tumor,mitotic,microtubule-targeted,arrest,Inhibitor,potent,subnanomolar,Maytansine,inhibit;(14S,16S,32S,33S,2R,4S,10E,12E,14R)-86-Chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl N-acetyl-N-methyl-L-alaninate
- CBNumber:
- CB8903295
- Summenformel:
- C34H46ClN3O10
- Molgewicht:
- 692.2
- MOL-Datei:
- 35846-53-8.mol
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Maitansin Eigenschaften
- Schmelzpunkt:
- 183.5-184℃
- alpha
- D26 -145° (c = 0.055 in chloroform)
- Siedepunkt:
- 895.1±65.0 °C(Predicted)
- Dichte
- 1.1049 (rough estimate)
- Brechungsindex
- 1.6000 (estimate)
- storage temp.
- Store at -20°C
- Löslichkeit
- DMF: 1 mg/ml; DMSO: 10 mg/ml; Ethanol: 2 mg/ml; PBS (pH 7.2): insol
- Aggregatzustand
- A solid
- pka
- 9.82±0.70(Predicted)
- Stabilität:
- Light Sensitive
- InChIKey
- WKPWGQKGSOKKOO-YHBUUTGONA-N
Sicherheit
- Risiko- und Sicherheitserklärung
- Gefahreninformationscode (GHS)
Toxizität |
LD50 in rats (mg/kg): 0.48 s.c. (Mugera, Ward) |
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Bildanzeige (GHS) |
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Alarmwort |
Achtung |
Gefahrenhinweise |
Code |
Gefahrenhinweise |
Gefahrenklasse |
Abteilung |
Alarmwort |
Symbol |
P-Code |
H331 |
Giftig bei Einatmen. |
Akute Toxizität inhalativ |
Kategorie 3 |
Achtung |
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P261, P271, P304+P340, P311, P321,P403+P233, P405, P501 |
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Sicherheit |
P261 |
Einatmen von Staub vermeiden. |
P262 |
Nicht in die Augen, auf die Haut oder auf die Kleidung gelangen lassen. |
P264 |
Nach Gebrauch gründlich waschen. |
P264 |
Nach Gebrauch gründlich waschen. |
P270 |
Bei Gebrauch nicht essen, trinken oder rauchen. |
P271 |
Nur im Freien oder in gut belüfteten Räumen verwenden. |
P280 |
Schutzhandschuhe/Schutzkleidung/Augenschutz tragen. |
P301+P310 |
BEI VERSCHLUCKEN: Sofort GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen. |
P302+P352 |
BEI BERÜHRUNG MIT DER HAUT: Mit viel Wasser/... (Hersteller kann, falls zweckmäßig, ein Reinigungsmittel angeben oder, wenn Wasser eindeutig ungeeignet ist, ein alternatives Mittel empfehlen) waschen. |
P304+P340 |
BEI EINATMEN: Die Person an die frische Luft bringen und für ungehinderte Atmung sorgen. |
P311 |
GIFTINFORMATIONSZENTRUM/Arzt anrufen. |
P321 |
Besondere Behandlung |
P330 |
Mund ausspülen. |
P403+P233 |
An einem gut belüfteten Ort aufbewahren. Behälter dicht verschlossen halten. |
P405 |
Unter Verschluss aufbewahren. |
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Maitansin Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
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 ED
50 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.
Verwenden
Antineoplastic.
Definition
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.
Biologische Funktion
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.
Toxikologie
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.
Einzelnachweise
Walpert-Defillipes et al., Biochem. Pharmacol., 24, 751 (1975)
Maitansin Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Maytansine, 3-O-de[2-(acetylmethylamino)-1-oxopropyl]-4,5-deepoxy-4,5-didehydro-, (4E)- (9CI)
Spiro[2-azabicyclo[16.3.1]docosa-1(22),6,13,15,18,20-hexaene-11,2'-[1,3]dithian]-3-one, 21-chloro-5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-9-hydroxy-12,20-dimethoxy-2,6,8,16-tetramethyl-, [5S-(5R*,6E,8R*,9R*,12S*,13E,15E)]- (9CI)
Maytansine, 3-O-de[2-(acetylmethylamino)-1-oxopropyl]-4,5-deepoxy-4,5-didehydro-9-O-methyl-, (4E)- (9CI)
Maytansine, 3-O-de[2-(acetylmethylamino)-1-oxopropyl]-4,5-deepoxy-4,5-didehydro-3-O-[(1,1-dimethylethyl)dimethylsilyl]-, (4E)- (9CI)
Spiro[2-azabicyclo[16.3.1]docosa-1(22),6,13,15,18,20-hexaene-11,2'-[1,3]dithian]-3-one, 9-[(aminocarbonyl)oxy]-21-chloro-5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-12,20-dimethoxy-2,6,8,16-tetramethyl-, [5S-(5R*,6E,8R*,9R*,12S*,13E,15E)]- (9CI)
Downstream Produkte
Maitansin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.
Global( 69)Lieferanten
35846-53-8(Maitansin)Verwandte Suche:
- maitansine
- Maytansine
- NSC 153858
- (14S,16S,32S,33S,2R,4S,10E,12E,14R)-86-Chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl N-acetyl-N-methyl-L-alaninate
- Maitansina
- Microtubule/Tubulin,tumor,mitotic,microtubule-targeted,arrest,Inhibitor,potent,subnanomolar,Maytansine,inhibit
- 35846-53-8
- 35845-53-8
- C34H46ClN3O10