Patupilone
[CAS# 152044-54-7]

Identification

• Classification: API >> Antibiotics >> Other antibiotics
• Name: Patupilone
• Synonyms: (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione; Epothilone B
• Molecular Formula: C₂₇H₄₁NO₆S
• Molecular Weight: 507.68
• CAS Registry Number: 152044-54-7
• EC Number: 604-822-6
• SMILES: C[C@H]1CCC[C@@]2([C@@H](O2)C[C@H](OC(=O)C[C@@H](C(C(=O)[C@@H]([C@H]1O)C)(C)C)O)/C(=C/C3=CSC(=N3)C)/C)C

Properties

• Density: 1.1±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.532, Calc.^*
• Boiling Point: 680.2±55.0 °C (760 mmHg), Calc.^*
• Flash Point: 365.2±31.5 °C, Calc.^*

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

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07;GHS08;GHS09 Danger
• Risk Statements: H300-H301-H310-H315-H317-H318-H335-H341-H351-H360-H361-H372-H400-H410
• Safety Statements: P203-P260-P261-P262-P264-P264+P265-P270-P271-P272-P273-P280-P301+P316-P302+P352-P304+P340-P305+P354+P338-P316-P317-P318-P319-P321-P330-P332+P317-P333+P317-P361+P364-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Germ cell mutagenicity	Muta.	2	H341
Skin irritation	Skin Irrit.	2	H315
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Skin sensitization	Skin Sens.	1	H317
Acute toxicity	Acute Tox.	1	H300
Reproductive toxicity	Repr.	1B	H360
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	2	H310
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Acute toxicity	Acute Tox.	2	H300
Carcinogenicity	Carc.	2	H351
Acute toxicity	Acute Tox.	3	H301
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin sensitization	Skin Sens.	1A	H317

Discovery and Applications

Patupilone, also known as Epothilone B, is a naturally occurring compound originally isolated from the myxobacterium Sorangium cellulosum. Its discovery stemmed from efforts to find novel microtubule-stabilizing agents akin to paclitaxel. Patupilone was identified for its potent anticancer activity, particularly against paclitaxel-resistant cell lines, and its ability to overcome multidrug resistance mechanisms.

Patupilone exhibits promising efficacy against various solid tumors, including ovarian, breast, and lung cancers, by disrupting microtubule dynamics and inducing apoptosis in cancer cells. Unlike paclitaxel, patupilone does not rely on the P-glycoprotein efflux pump for cellular uptake, making it effective against multidrug-resistant tumors. Clinical studies have shown favorable outcomes in patients with advanced cancers, both as monotherapy and in combination with other chemotherapeutic agents. Additionally, patupilone has demonstrated potential for the treatment of brain tumors due to its ability to penetrate the blood-brain barrier. While further research is needed to optimize its therapeutic profile and mitigate side effects, patupilone represents a promising addition to the arsenal of anticancer drugs, particularly for patients resistant to conventional chemotherapies.

References

2024. Microtubule-Targeting Agents: Disruption of the Cellular Cytoskeleton as a Backbone of Ovarian Cancer Therapy. Advances in experimental medicine and biology, 1456, 1-16.
DOI: 10.1007/978-3-031-58311-7_1

2023. Epothilone B loaded in acellular nerve allograft enhanced sciatic nerve regeneration in rats. Fundamental & Clinical Pharmacology, 37, 1082-1092.
DOI: 10.1111/fcp.12961

1997. Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(R)). The Journal of biological chemistry, 272, 2534-2541.
DOI: 10.1074/jbc.272.4.2534