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外観
白色～わずかにうすい褐色、結晶性粉末～粉末
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溶解性
メタノール溶状：試験適合
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用途
ヨーロッパイチイの針状葉か
ら抽出された 10- デアセチルバッカチンⅢか
ら半合成されたタキソイド系抗がん剤の有効
成分です。チューブリンの重合を促進し、脱
重合を阻害することにより、細胞分裂を阻害
します。
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効能
抗悪性腫瘍薬, 微小管脱重合阻害薬
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説明
In June 2010, the U.S. FDA approved cabazitaxel (also referred to as
XRP6258 and RPR 116258A) in combination with the steroid prednisone
for the treatment of metastatic Castration-Resistant Prostate Cancer
(mCRPC) for patients who were previously treated with a docetaxelcontaining
regimen for late-stage disease.
Cabazitaxel is a semisynthetic analog of the
natural product taxol, which is isolated from the bark of the yew tree.
Cabazitaxel is a microtubule inhibitor that binds to the taxol-binding site of
tubulin. Similar to other tubulin inhibitors of the taxol class, cabazitaxel
inhibits microtubule disassembly resulting in mitotic blockade and cell
death. Docetaxel, also a semisynthetic taxol analog, was approved by the
FDA for the treatment of mCRPC in 2004. However, docetaxel is a substrate
for P-gp, which is thought to contribute to the constitutive and acquired
resistance of cancer cells to taxanes. Cabazitaxel has poor affinity for P-gp
and showed antitumor activity in preclinical in vitro studies and in vivo
tumor models that overexpress this protein. Cabazitaxel is synthesized on
a commercial scale from 10-deacetylbaccatin .
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化学的特性
White solid
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使用
Cabazitaxel (Jevtana, XRP6258) is a semi-synthetic derivative of a natural taxoid.
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定義
ChEBI: A tetracyclic diterpenoid that is 10-deacetylbaccatin III having O-methyl groups attached at positions 7 and 10 as well as an O-(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hy
roxy-3-phenylpropanoyl group attached at position 13. Acts as a microtubule inhibitor, binds tubulin and promotes microtubule assembly and simultaneously inhibits disassembly.
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臨床応用
Cabazitaxel was developed by Sanofi-Aventis as an intravenous injectable drug for the treatment of
hormone-refractory metastatic prostate cancer. As a microtubule inhibitor, cabazitaxel differs from docetaxel because it exhibits a much weaker affinity for P-glycoprotein (P-gp), an adenosine
triphosphate (ATP)-dependent drug efflux pump. Cancer cells that express P-gp become resistant
to taxanes, and the effectiveness of docetaxel can be limited by its high substrate affinity for P-gp.
Clinical studies confirmed that cabazitaxel retains activity in docetaxel-resistant tumors. Common
adverse events with cabazitaxel include diarrhea and neutropenia. Cabazitaxel in combination with
prednisone is an important new treatment option for men with docetaxel-refractory metastatic CRPC
(castration-resistant prostate cancer).
