| IUPAC Name | (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione |
| InChI | InChI=1S/C27H42N2O5S/c1-15-9-8-10-27(7)22(34-27)12-20(16(2)11-19-14-35-18(4)28-19)29-23(31)13-21(30)26(5,6)25(33)17(3)24(15)32/h11,14-15,17,20-22,24,30,32H,8-10,12-13H2,1-7H3,(H,29,31)/b16-11+/t15-,17+,20-,21-,22-,24-,27+/m0/s1 |
| Reference | 1. Expert Opin Investig Drugs. 2008 Mar;17(3):423-35. doi: 10.1517/13543784.17.3.423
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<br><br>
Ixabepilone for the treatment of solid tumors: a review of clinical data.
<br><br>
Denduluri N(1), Swain SM.
<br>
Author information: <br>
(1)National Cancer Institute, National Institutes of Health, Breast Cancer
Section, Medical Oncology Branch, Center for Cancer Research, 10 Center Drive,
Room 12N226, Bethesda, Maryland 20892, USA.
<br>
BACKGROUND: Microtubule stabilizing agents such as taxanes are an integral part
of therapy for multiple solid tumors. However, due to limitations of these
agents, newer more effective cytotoxic agents are necessary. Ixabepilone, an
epothilone B analog, is a novel microtubule stabilizing agent.<br>
OBJECTIVE: This review provides an updated summary of emerging clinical
experience with Ixabepilone.<br>
METHODS: Phase I, II and III clinical trials presented in abstract form or
journal articles found within a PubMed search through November 2007 are described
in this review.<br>
RESULTS/CONCLUSION: Ixabepilone offers promising clinical activity in a variety
of solid tumors. Ixabepilone is FDA-approved for the treatment of breast cancer
refractory to anthracyclines and taxanes. The optimal dose and schedule are still
being defined, and the predominant side effects are bone marrow suppression and
neuropathy.
<br><br>
2. Clin Breast Cancer. 2007 Oct;7(10):757-63.
<br><br>
Ixabepilone, first in a new class of antineoplastic agents: the natural
epothilones and their analogues.
<br><br>
Fornier MN(1).
<br>
Author information: <br>
(1)Breast Cancer Medicine Service, Division of Solid Tumor Oncology, Department
of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
[email protected]
<br>
Although targeted therapies are becoming increasingly important in oncology,
cytotoxic agents are likely to remain a valuable element in the treatment
paradigm of cancer. However, resistance to chemotherapy is a major obstacle to
the successful treatment of cancer. Therefore, there is a need for novel
antineoplastic agents that are able to overcome mechanisms of tumor resistance.
Drugs that target microtubules, including paclitaxel and docetaxel, are among the
most commonly prescribed anticancer therapies. However, the utility of
taxane-based therapies is limited by difficulties with formulation,
administration, and resistance induced by P-glycoprotein. The epothilones and
their analogues are a novel class of antimicrotubule agents that has demonstrated
antitumor activity in the setting of resistance. These antimicrotubule agents are
structurally unrelated to the taxanes, with a distinct beta-tubulin-binding mode.
Ixabepilone is a rationally designed, semisynthetic analogue of natural
epothilone B, which displays reduced susceptibility to a range of common tumor
resistance mechanisms. Promising phase II activity and a manageable safety
profile with ixabepilone have been seen in a wide range of tumor types, including
heavily pretreated/resistant and early-stage breast cancer. Moreover, encouraging
phase III results with ixabepilone and capecitabine for patients with breast
cancer have recently been presented. Clinical trials are also planned for
ixabepilone in combination with targeted agents, such as trastuzumab and
bevacizumab. Ixabepilone is likely to be the first available drug in its class,
with the potential to bring clinical benefit to patients with a wide range of
malignancies.
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