Home Cytoskeletal Signaling ADC Cytotoxin inhibitor - Microtubule Associated inhibitor Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222)

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Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222) ADC Cytotoxin inhibitor

Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222, Antibiotic C 15003P3) is a potent inhibitor of tubulin polymerization with IC50 of 3.4 μM.

Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222) ADC Cytotoxin inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 635.14

Purity & Quality Control

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Mechanism of Action

Features Ansamitocin p-3 does not inhibit the growth of bacteria, but very markedly inhibits the growth of eukaryotic organisms.

In vitro
In vitro

Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222) at 5 μM completely inhibits the polymerization of tubulin isolated from bovine brains, but in contrast to VCR, this compound at a high concentration of 80 μM does not leads to the aggregation of tubulin. It at 16 μM also potently depolymerizes the polymerized tubulin (IC50 = 3.8 μM). The addition of Ansamitocin p-3 to culture cells blocks the morphological alteration of AC cells from fibroepithelioid to a glial cell type caused by the exposure to a certain concentration of dibutyryl cyclic adenosine 3':5'-monophosphate. In addition, treatment with it at 16 nM causes the well-defined network of cytoplasmic microtubules of A31 cells rapidly dispersed. Short-term Ansamitocin p-3 treatment also inhibits the synthesis of DNA in A31 cells or KB cells. These results confirm that it acts by interfering with the microtubule assembly system, thus resulting in an inhibition of mitotic spindle fiber formation and, ultimately, cytokilling. [1] This compound displays potent cytotoxicity against A-549, HT-29, and MCF-7 cells in a dose-dependent manner with ED50 of 4 ×10-7, 4 × 10-7, and 2 × 10-6 μg/mL, respectively. [2] It also exhibits cytotoxicity against HCT-116 cells with a much low EC50 of 0.081 nM. [3] Ansamitocin p-3 enhances the effect of radiation both in Drosophila cells and human cancer cells in a p53 dependent manner. [4]
Kinase Assay Polymerization inhibition assay
After the addition of 100 μL of various concentrations of Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222) solution (GTP minus MES buffer) or 1 M Tris buffer, pH 8.4 (for blank), to 400 μL of bovine tubulin solution (1 mg/mL in cold MES buffer), maintained at 0 °C for 10 to 15 minutes, the mixture is warmed in a water bath at 37 °C for 30 to 60 minutes. The polymerization of tubulin is followed by an increase in turbidity of the mixture during warming. The turbidity measurement is performed at 460 nm with a Hitachi type 101 spectrophotometer.
Cell Research Cell lines A31 and KB
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time ~24 hours
Method

Cells are synchronized, and then exposed to various concentrations of Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222) for ~24 hours. After pulse-labeling at 37 °C for 1 hour with [3H]thymidine (5 Ci/mM, 1 μCi/mL) in 1 mL of the medium, the cells on coverslips are fixed with methanol:acetic acid (3:1). The acid-soluble fraction is washed out from the cells, and the radio activity of each coverslip is determined by a liquid scintillation counter.

In Vivo
In vivo

Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222) treatment (>1 μg) significantly suppresses the growth of leukemia SN36, and induces an increased arrest in metaphase of P388 leukemia cells. At 25 μg/kg/day, it significantly prolongs the survival time of mice bearing i.p. B16 melanoma by 130%. This compound also significantly prolongs the survival time of mice bearing Ehrlich ascites carcinoma, Sarcoma 180, and P815 mastocytoma, while slightly prolonging the survival time of mice bearing ascites MOPC-104E myeloma, leukemia L1210, and leukemia C1498. [1]
Animal Research Animal Models Female DBA/2 mice bearing P388, L1210, or P815 cells, C57BL/6 mice bearing B16, or C1498 cells, ICR mice bearing sarcoma 180 and EAC, and BALB/c mice bearing MOPC-104E cells
Dosages ~200 μg/kg
Administration Administered i.p. or i.v. daily

References
  • https://pubmed.ncbi.nlm.nih.gov/6245801/
  • https://pubmed.ncbi.nlm.nih.gov/2298279/
  • https://pubmed.ncbi.nlm.nih.gov/16314405/
  • https://pubmed.ncbi.nlm.nih.gov/21504911/
  • https://pubmed.ncbi.nlm.nih.gov/24124473/

Chemical Information

Molecular Weight 635.14 Formula

C32H43ClN2O9
CAS No. 66584-72-3 SDF --
Synonyms Antibiotic C 15003P3
Smiles CC1C2CC(C(C=CC=C(CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)CC(C4(C1O4)C)OC(=O)C(C)C)C)C)OC)(NC(=O)O2)O

Storage and Stability

Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (157.44 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 55 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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