Ansamitocin P 3
[CAS# 66584-72-3]

Identification

• Classification: API >> Antiparasitic drug >> Anthelmintic medications
• Name: Ansamitocin P 3
• Synonyms: Ansamitosin P 3; Antibiotic C 15003P3; Maytansinol isobutyrate; NSC 292222; 2'-De(acetylmethylamino)-2'-methylmaytansine
• Molecular Formula: C₃₂H₄₃ClN₂O₉
• Molecular Weight: 635.14
• CAS Registry Number: 66584-72-3
• EC Number: 680-663-6
• SMILES: C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C/C=C(/CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@@H]([C@]4([C@H]1O4)C)OC(=O)C(C)C)C)C)OC)(NC(=O)O2)O

Properties

• Density: 1.3±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.583, Calc.^*
• Boiling Point: 833.1±65.0 °C (760 mmHg), Calc.^*
• Flash Point: 457.7±34.3 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302+H332-H302-H315-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	1	H310
Acute toxicity	Acute Tox.	1	H300
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	2	H330
Acute toxicity	Acute Tox.	1	H330
Germ cell mutagenicity	Muta.	1B	H340
Acute toxicity	Acute Tox.	2	H300
Reproductive toxicity	Repr.	1B	H360FD
Specific target organ toxicity - single exposure	STOT SE	2	H371

Discovery and Applications

Ansamitocin P 3 is a member of the ansamycin family of compounds originally isolated from Actinosynnema pretiosum, a soil bacterium, in the 1970s. Its discovery was driven by the search for novel antitumor agents with distinct mechanisms of action. Ansamitocin P 3 attracted attention for its potent cytotoxicity against cancer cells and its unique mode of action involving inhibition of tubulin polymerization.

Ansamitocin P 3 and its derivatives, such as maytansine and DM4, have been extensively studied for their potential in cancer therapy. These compounds serve as payloads for antibody-drug conjugates (ADCs), enabling targeted delivery of cytotoxic agents to cancer cells while sparing healthy tissues. Notably, ansamitocin P 3 is utilized in the ADC ado-trastuzumab emtansine (T-DM1) for the treatment of HER2-positive breast cancer. T-DM1 has demonstrated efficacy in patients who have progressed on prior HER2-targeted therapies and cytotoxic chemotherapy, offering a promising option for advanced disease. The success of T-DM1 underscores the therapeutic potential of ansamitocin P 3-based ADCs in oncology. Ongoing research aims to optimize ADC design, enhance tumor specificity, and broaden the utility of ansamitocin P 3 derivatives in the treatment of various malignancies, further solidifying their role in cancer therapy.

References

2023. Biosynthesis of ansamitocin P-3 incurs stress on the producing strain Actinosynnema pretiosum at multiple targets. Communications Biology, 6(1).
DOI: 10.1038/s42003-023-05227-w

2015. Improvement of Ansamitocin P-3 Production by Actinosynnema mirum with Fructose as the Sole Carbon Source. Applied Biochemistry and Biotechnology, 175(2).
DOI: 10.1007/s12010-014-1445-6

1982. Biosynthetic origin of aminobenzenoid nucleus (C7N-unit) of ansamitocin, a group of novel maytansinoid antibiotics. The Journal of Antibiotics, 35(10).
DOI: 10.7164/antibiotics.35.1415