Paclitaxel

September 21, 2020
I’m a venerable cancer drug that has had its share of controversy.
What molecule am I?

Paclitaxel, commonly known by its trade name Taxol, is a chemotherapy drug that has been used to treat many types of cancer. Despite its several adverse side effects, it is on the World Health Organization's List of Essential Medicines.

In 1971, as the sixth part of a series of articles on plant antitumor agents, Mansukh C. Wani and colleagues at the Research Triangle Institute (NC) and Duke University (Durham, NC) reported the isolation of a complex molecule from the bark of the Pacific yew tree (Taxus brevifolia) that they named “taxol”. In the article’s introduction, the authors state, “Taxol has potent antileukemic and tumor inhibitory properties and is the first compound possessing the taxane ring [that] has been demonstrated to have such activity.” The taxane “ring” is actually a tricyclic structure that forms the core of the molecule (see images).

Wani et al. provided very little information about “taxol’s” anticancer activity; the article focused on the chemistry and spectra of the compound and some of its derivatives. During the next two decades, Wani, his colleague Monroe E. Wall, and several other researchers, under the auspices of the National Cancer Institute (NCI), investigated the potential drug’s activity against various cancers. They began clinical trials in 1984. During the 1970s and ’80s, almost 10 t of Pacific yew bark were harvested and extracted for experimental work and the trials.

Finally, in 1989, NCI offered to turn the project over to a commercial pharmaceutical company. The offer generated surprisingly little interest; but by the end of the year, the technology was transferred to Bristol-Meyers Squibb (BMS)—the same year that the BMS merger was concluded. BMS obtained the generic name paclitaxel for the drug and registered the brand name Taxol with the US Office of Patents and Trademarks. The NCI–BMS deal and the trademarked name soon became the subject of much controversy.

BMS received its first drug approval for paclitaxel from the US Food and Drug Administration in 1992. As of 2018, FDA approvals include treatment of breast, pancreatic, ovarian, and non–small-cell lung cancers; and Kaposi's sarcoma. Paclitaxel has been extremely thoroughly researched: As of this writing, SciFinder lists 73,164 references, including mentions in 68 United States and international patents.

Paclitaxel hazard information*

Hazard class** Hazard statement
Acute toxicity, oral, category 4 H302—Harmful if swallowed Chemical Safety Warning
Acute toxicity, dermal, category 4 H312—Harmful in contact with skin Chemical Safety Warning
Skin corrosion/irritation, category 2 H315—Causes skin irritation Chemical Safety Warning
Skin sensitization, category 1 H317—May cause an allergic skin reaction Chemical Safety Warning
Serious eye damage/eye irritation, category 1 H318—Causes serious eye damage  Chemical Safety Warning
Acute toxicity, inhalation, category 4 H332—Harmful if inhaled Chemical Safety Warning
Respiratory sensitization, category 1 H334—May cause allergy or asthma symptoms or breathing Chemical Safety Warning
Specific target organ toxicity, single exposure, respiratory tract irritation, category 3 H335—May cause respiratory irritation Chemical Safety Warning
Germ cell mutagenicity, category 2 H341—Suspected of causing genetic defects Chemical Safety Warning
Reproductive toxicity, category 1B H360—May damage fertility or the unborn child Chemical Safety Warning
Hazardous to the aquatic environment, long-term hazard, category 4  H413—May cause long-lasting harmful effects to aquatic life

 *Globally Harmonized System of Classification and Labeling of Chemicals.
Explanation of pictograms.

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Paclitaxel fast facts

CAS Reg. No. 33069-62-4
SciFinder
nomenclature
See SciFinder listing
Empirical formula C47H51NO14
Molar mass 853.91 g/mol
Appearance White crystalline powder
Melting point 213–216 ºC
Water solubility  ≈10–20 mg/L (est.)

MOTW update

N-Nitrosodimethylamine (NDMA) was the Molecule of the Week for January 14, 2019. It is used to make rocket fuel; but, because it is extremely toxic, it is notorious for its use in some fatal poisonings. NDMA and other nitrosamines have been found as impurities in several prescription drugs. Earlier this month, the US Food and Drug Administration issued guidelines on acceptable limits of six nitrosamine impurities. The limit set for NDMA is 96 ng/day.

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