66547-09-9

Basic information

• Product Name: ANSAMITOCIN P-3
• Synonyms: 3-de(2-(acetylmethylamino)propionyloxy)-3-hydroxy-maytansinbutyrate(ester;3-de(2-(acetylmethylamino)propionyloxy)-3-hydroxymaytansinebutyrate(ester);antibioticc15003p3’;c15003p-3’;maytansine,o(sup3)-de(2-(acetylmethylamino)-1-oxopropyl)-o(sup3)-(1-oxobut;maytansinolbutyrate;ASMP-3;ANSAMITOCIN P-3, ACTINOSYNNEMA PRETIOSUM
• CAS NO: 66547-09-9
• Molecular Formula: C₃₂H₄₃ClN₂O₉
• Molecular Weight: 635.14
• Product Categories: Microtobule Inhibitors;Cell Signaling and Neuroscience;Cytoskeleton and Extracellular Matrix;Cytoskeleton and Extracellular Matrix;Microtobule Inhibitors;Cell Signaling and Neuroscience;Inhibitors
• Mol File: 66547-09-9.mol
• Article Data: 1

Chemical Properties

• Melting Point: 182-185℃
• Boiling Point: 837.6°Cat760mmHg
• Flash Point: 460.4°C
• Appearance: /
• Density: 1.30±0.1 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 8.97E-30mmHg at 25°C
• Refractive Index: 1.584
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO (up to 50 mg/ml) or in Ethanol (up to 30 mg/ml with warming).
• PKA: 9.83±0.70(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months.
• CAS DataBase Reference: ANSAMITOCIN P-3(CAS DataBase Reference)
• NIST Chemistry Reference: ANSAMITOCIN P-3(66547-09-9)
• EPA Substance Registry System: ANSAMITOCIN P-3(66547-09-9)

Safety Data

• Hazard Codes: Xn
• Statements: 20/22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: OQ2293000
• Hazardous Substances Data: 66547-09-9(Hazardous Substances Data)

Usage

Description

Ansamitocin P-3 is a microtubule depolymerizing agent that can be isolated from culture broths of certain Gram-positive bacteria. It binds tubulin (Kd = 1.3 μM), depolymerizes microtubules in both interphase and mitosis, and perturbs chromosome segregation. Ansamitocin P-3 also activates the spindle checkpoint surveillance proteins Mad2 and BubR1, blocking cell cycling during mitosis. It inhibits the growth of cancer cells in culture and significantly suppresses the growth of several cancer tumors in mice, prolonging survival time.

Uses

Ansamitocin P-3’ is a metabolite of Ansamitocin which is a new maytansinoid antitumor antibiotic.

References

1) Li et al (1992) Binding selectivity of rhizoxin, phomopsin A, vinblastine and ansamitocin P-3 to fungal tubulins: differential interactions of thes antimitotic agents with brain and fungal tubulins; Biochem. Biophys. Res. Commun., 187 722 2) Venghateri et al. (2013) Ansamitocin P3 Depolymerizes Microtubules and Induces Apoptosis by Binding Tubulin at the Vinblastine Site; PLoS ONE 8 e75182 3) Suwanborirux et al. (1990) Ansamitocin P-3, a maytansinoid, from claopodium crispifolium and anomodo attenuates or associated actinomycetes; Experientia, 46 117 4) Ootsu et al. (1980) Effects of new antimitotic antibiotics, ansamitocins, on the growth of murine tumors in vivo and on the assembly of microtubules in vitro; Cancer Res. 40 1707

InChI:InChI=1/C32H43ClN2O9/c1-8-10-27(37)43-25-16-26(36)35(5)21-14-20(15-22(40-6)28(21)33)13-18(2)11-9-12-24(41-7)32(39)17-23(42-30(38)34-32)19(3)29-31(25,4)44-29/h9,11-12,14-15,19,23-25,29,39H,8,10,13,16-17H2,1-7H3,(H,34,38)/b12-9+,18-11-/t19-,23+,24-,25-,29+,31+,32+/m1/s1

Upstream product

• 57103-68-1 maytansinol 
• 107-92-6 butyric acid 

Relevant articles and documents

Chemical modification of ansamitocines. III. Synthesis and biological effects of 3-acyl esters of maytansinol

Several semisynthetic maytansinoids that differ in the structure of the acyl group at the C3 position were prepared by acylation of maytansinol (3) using appropriate carboxylic acids or their active derivatives, and the effects of the compounds on the growth of Tetrahymena pyriformis and the survival of tumor-bearing mice were determined. Among these analogs, the C3 esters having a straight chain aliphatic acyl (11, 12), cycloalkanecarbonyl (18-20) or phenylacetyl group (22), and those having a 2-(N-acetyl-N-methyl)aminohexanoyl (7) or (2-(N-acetyl-N-methyl)aminophenylpropionyl group (8), strongly inhibited the growth of T. pyriformis and exhibited potent activity against B16 melanoma in mice. The potencies were similar to those of maytansine and ansamitocin P-3. The most striking result was the finding that the phenylglycinate (31) was superior to maytansine in terms of its broader effective dose range against ip B16 melanoma and P388 leukemia in mice; however, higher doses of the phenylglycinate were required.