Paclitaxel

Paclitaxel is a renowned diterpene alkaloid that has garnered significant attention from scientists due to its distinctive chemical structure, unique mechanism of action, potent anticancer properties, and the challenges associated with its supply.

Discovered in 1967 by Dr. Monroe Wall and Dr. Mansukh Wani at the Research Triangle Institute, paclitaxel was originally isolated from the bark of the Pacific yew tree, Taxus brevifolia. Its chemical formula is C47H51NO14, and its structure is characterized by a complex, polycyclic diterpenoid core featuring a taxane ring system. Key to its biological activity are the ester side chain at the C13 position and an oxetane ring spanning the C4-C5 positions.

Product Detail

Product Name	Paclitaxel
CAS No.	33069-62-4
Catalog	ALKS33069624
Molecular Weight	853.91
Molecular Formula	C47H51NO14
Purity	≥ 98%
Appearance	White powder
Melting Point	213 - 216 °C
Solubility	Insoluble in water, decomposes quickly under alkaline conditions
Extraction Source	Bark of Taxus brevifolia, a plant belonging to the family Taxaceae
Pharmacological Efficacy	Paclitaxel is mainly suitable for ovarian cancer and breast cancer
Storage	Refrigerated at 4 °C, sealed, and protected from light (valid for 2 years under this condition)

Mechanism of Action

Paclitaxel is widely used in the treatment of various types of cancer. It works by disrupting the normal function of microtubules in cells. Microtubules are essential components of the cell’s cytoskeleton and are crucial for cell division. Paclitaxel stabilizes the microtubule polymer and protects it from disassembly, resulting in the inhibition of the mitotic process. This disruption leads to cell cycle arrest and ultimately cell death (apoptosis).

Interaction with Microtubules

Stabilization of Microtubules

Paclitaxel binds specifically to the β-tubulin subunit of microtubules. Normally, microtubules must polymerize and depolymerize dynamically to perform their functions, particularly during cell division. Paclitaxel stabilizes microtubules by promoting their polymerization and preventing their depolymerization. This stabilization locks the microtubules in a polymerized state, disrupting their dynamic equilibrium.

Inhibition of Mitotic Spindle Formation

During mitosis, microtubules form the mitotic spindle, a structure that separates duplicated chromosomes into two daughter cells. The stabilization caused by paclitaxel disrupts the normal formation and function of the mitotic spindle. This disruption leads to the failure of chromosome segregation, causing cell cycle arrest at the metaphase-anaphase transition.

Induction of Apoptosis

The arrest of the cell cycle and inability to proceed through mitosis trigger a series of cellular events leading to programmed cell death (apoptosis). This is a crucial mechanism for paclitaxel's antitumor effects. Apoptosis is facilitated by various signaling pathways activated in response to prolonged mitotic arrest and the resulting cellular stress.

Detailed Molecular Interactions

Binding Site

Paclitaxel binds to the β-tubulin subunit within the microtubule lumen, at a specific site known as the taxane-binding site. This binding is high-affinity and highly specific, leading to significant changes in the microtubule’s properties.

Conformational Changes

The binding of paclitaxel induces conformational changes in the microtubule structure, promoting a more stable configuration. These changes enhance the microtubule's resistance to depolymerizing factors, further stabilizing the polymerized state.

Choose Alfa Chemistry

At Alfa Chemistry, we are dedicated to offering industry-leading alkaloid products. Our top-quality paclitaxel stands as a dependable choice for researchers and scientists. If you are in need of this exceptional compound, don't hesitate to reach out to us today.