ixabepilone
Trade name: ixempra
Small moleculeapproved
Approved
Oct 16, 2007
Ixabepilone is an antineoplastic agent, epothilone and mitotic inhibitor that is FDA approved for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Ixabepilone binds directly to beta-tubulin subunits on microtubules, leading to suppression of microtubule dynamics. Ixabepilone suppresses the dynamic instability of alpha-beta-II and alpha-beta-III microtubules. The most common adverse reactions (≥20%) are peripheral sensory neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/mucositis, diarrhea, and musculoskeletal pain. Inhibitors of CYP3A4 may increase plasma concentrations of ixabepilone. — NCATS
Clinical trial activity
116 trials · 63 clinical orgs · 2 marketing orgs
Phase 1
43
Phase 2
85
Phase 3
10
Phase 4
0
Earliest trial started Jul 1, 1999 (NCT00004927)
Timeline
2000s
- Jan 1, 2001
Earliest Phase 2 Sponsor(trial)
- Jan 1, 2003
- Oct 16, 2007
Bristol-Myers Squibb — Earliest FDA Approval
- Oct 16, 2007
R-Pharm — NDA Secondary Org
- Oct 16, 2007
Bristol-Myers Squibb — NDA Organization
Indications
Approved for
Studied for
- Adenocarcinoma · Phase 2
- Astrocytoma · Phase 1/Phase 2
- Bile Duct Neoplasms · Phase 2
- Brain Neoplasms · Phase 2
- Breast Neoplasms, Male · Phase 2
- Burkitt Lymphoma · Phase 2
- Carcinoma · Phase 2
- Carcinoma, Hepatocellular · Phase 2
- Carcinoma, Non-Small-Cell Lung · Phase 2
- Carcinoma, Ovarian Epithelial · Phase 2
- Carcinoma, Renal Cell · Phase 2
- Carcinoma, Squamous Cell · Phase 2
- Carcinoma, Verrucous · Phase 2
- Cholangiocarcinoma · Phase 2
- Colonic Neoplasms · Phase 1
- Colorectal Neoplasms · Phase 2
- Endometrial Neoplasms · Phase 3
- Esophageal Neoplasms · Phase 2
- Fallopian Tube Neoplasms · Phase 2
- Gallbladder Neoplasms · Phase 2
- Genital Diseases, Male · Phase 2
- Genital Neoplasms, Male · Phase 2
- Glioblastoma · Phase 1/Phase 2
- Gliosarcoma · Phase 1/Phase 2
- Graft vs Host Disease · Phase 2
- Hamartoma · Phase 2
- Head and Neck Neoplasms · Phase 1/Phase 2
- Intestinal Neoplasms · Phase 1
- Kidney Neoplasms · Phase 1
- Leiomyosarcoma · Phase 2
- Leukemia · Phase 2
- Liver Neoplasms · Phase 2
- Lung Neoplasms · Phase 2
- Lymphoma · Phase 2
- Lymphoma, Follicular · Phase 2
- Lymphoma, Large-Cell, Anaplastic · Phase 2
- Lymphoma, Large-Cell, Immunoblastic · Phase 2
- Lymphoma, Mantle-Cell · Phase 2
- Melanoma · Phase 2
- Neoplasm Metastasis · Phase 3
- Neoplasms, Glandular and Epithelial · Phase 2
- Neuroblastoma · Phase 2
- Neutropenia · Phase 1
- Osteosarcoma · Phase 2
- Ovarian Neoplasms · Phase 2
- Pain · Phase 3
- Pancreatic Neoplasms · Phase 2
- Peripheral Nerve Injuries · Phase 3
- Prostatic Diseases · Phase 2
- Prostatic Neoplasms · Phase 2
- Rhabdomyosarcoma · Phase 2
- Salivary Gland Neoplasms · Phase 2
- Sarcoma · Phase 2
- Sarcoma, Ewing · Phase 2
- Sarcoma, Synovial · Phase 2
- Squamous Cell Carcinoma of Head and Neck · Phase 2
- Stomach Neoplasms · Phase 2
- Testicular Neoplasms · Phase 2
- Tongue Neoplasms · Phase 2
- Urethral Neoplasms · Phase 2
- Urinary Bladder Neoplasms · Phase 2
- Urogenital Neoplasms · Phase 2
- Uterine Cervical Neoplasms · Phase 2
- Uterine Neoplasms · Phase 2
- Wilms Tumor · Phase 2
Mechanism of action
- TubulinINHIBITOR
Tubulin inhibitor
Stabilises microtubule assembly
Binds to beta tubulin
- Tubulin beta-4B chain (TUBB4B) ↗
- Tubulin beta-1 chain (TUBB1) ↗
- Tubulin alpha-3C chain (TUBA3C) ↗
- Tubulin alpha-4A chain (TUBA4A) ↗
- Tubulin beta-3 chain (TUBB3) ↗
- Tubulin alpha-1A chain (TUBA1A) ↗
- Tubulin beta-4A chain (TUBB4A) ↗
- Tubulin beta-8 chain (TUBB8) ↗
- Tubulin beta chain (TUBB) ↗
- Tubulin alpha-1B chain (TUBA1B) ↗
- Tubulin alpha-1C chain (TUBA1C) ↗
- Tubulin alpha-3E chain (TUBA3E) ↗
- Tubulin beta-2A chain (TUBB2A) ↗
- Tubulin beta-2B chain (TUBB2B) ↗
- Tubulin beta-6 chain (TUBB6) ↗
Approval history
- approvedPriority reviewOct 16, 2007
Chemistry & pharmacology
Loading structure…
SMILES
C[C@H]1CCC[C@@]2(C)O[C@H]2C[C@H](NC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@H]1O)C(\C)=C\C3=CSC(C)=N3- Mol. weight
- 506.698 g/mol
- Lipinski Ro5
- 1 violation(s)
- Rule of 3
- No
- Chirality
- Single Stereoisomer
- Inorganic
- No
- Polymer
- No
- Delivery
- Parenteral
- Availability
- Prescription Only
Oral
No
Parenteral
Yes
Topical
No
Black box warning
Sources
- WikipediaIxabepilone ↗
- NCATSK27005NP0A ↗
- ChEMBLCHEMBL1201752 ↗
Also known as
- aza-epothilone b
- aza-epothilone b
- azaepothilone b
- azaepothilone b
- azaepothilone b
- azaepothilone b
- bms247550
- bms 247550
- bms-247550
- bms-247550
- bms-247550
- bms-247550
- bms-247550-01
- bms-247550-01
- ixabepilone
- ixabepilone
- ixabepilone
- ixabepilone
- ixabepilone
- ixabepilone
- ixabepilone
- ixabepilone
- ixabepilone
- ixabepilone
- ixabepilone
- ixempra
- ixempra
- ixempra
- ixempra
- ixempra
- ixempra kit
- ixempra kit
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT04796324 | Phase 2 | Mar 1, 2021 | Allarity Therapeutics |
| NCT03093155 | Phase 2 | Apr 3, 2017 | R-Pharm, Yale University |
| NCT02915744 | Phase 3 | Nov 1, 2016 | Nektar Therapeutics |
| NCT01349088 | Phase 1/Phase 2 (Phase 2) | Dec 1, 2013 | Amgen, Susan G. Komen Breast Cancer Foundation, Thomas Jefferson University |
| NCT01818999 | Phase 2 | Aug 1, 2013 | The University of Texas, Dallas |
| NCT02067416 | Phase 2 | Jul 1, 2012 | General Electric, Methodist Cancer Center, Houston, Texas, The Methodist Hospital System |
| NCT01492101 | Phase 3 | Dec 1, 2011 | Nektar Therapeutics |
| NCT01446016 | Phase 2 | Sep 1, 2011 | Methodist Cancer Center, Houston, Texas |
| NCT01416389 | Phase 2 | Aug 1, 2011 | Eli Lilly |
| NCT01375829 | Phase 1 | Jun 27, 2011 | Mayo Clinic, National Cancer Institute (NCI) |
| NCT01454479 | Phase 1 | Mar 1, 2011 | Bristol-Myers Squibb, Chang Gung University, GlaxoSmithKline |
| NCT01220609 | Phase 2 | Nov 1, 2010 | National Cancer Institute (NCI), NRG Oncology |
| NCT01168232 | Phase 2 | Sep 1, 2010 | Gynecologic Oncology Group, National Cancer Institute (NCI) |
| NCT01084057 | Phase 1 | May 17, 2010 | City of Hope National Medical Center |
| NCT01079793 | Phase 1/Phase 2 (Phase 2) | May 1, 2010 | National Cancer Institute (NCI), The University of Texas, Dallas |
| NCT01057212 | Phase 2 | Feb 1, 2010 | Bristol-Myers Squibb, Genentech, Providence Health & Services |
| NCT01075100 | Phase 2 | Jan 1, 2010 | Bristol-Myers Squibb, US Oncology |
| NCT01012362 | Phase 1 | Dec 1, 2009 | GlaxoSmithKline, University of Minnesota |
| NCT01170871 | Phase 1 | Nov 4, 2009 | University of Southern California |
| NCT00998738 | Phase 3 | Nov 1, 2009 | Mayo Clinic, National Cancer Institute (NCI) |
Showing 20 of 116 trials
Page 1 / 6
Organizations
Research & Development (63)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| National Cancer Institute (NCI) | Government | 55 | 31 | 3 | 1999 |
| Bristol-Myers Squibb | For profit | 46 | 4 | 3 | 2001 |
| R-Pharm | For profit | 29 | 28 | 3 | 1999 |
| Cornell University | Academic/Hospital | 9 | 7 | 2 | 1999 |
| SCRI Development Innovations | For profit | 5 | 5 | 2 | 2008 |
| Eastern Cooperative Oncology Group | Academic/Hospital | 4 | 0 | 1 | 2001 |
| Genentech | For profit | 4 | 0 | 2 | 2008 |
| The University of Texas, Dallas | Academic/Hospital | 4 | 2 | 1 | 2001 |
| University of Chicago | Academic/Hospital | 4 | 1 | 1 | 2001 |
| Yeshiva University | Academic/Hospital | 4 | 3 | 2 | 2000 |
| GlaxoSmithKline | For profit | 3 | 0 | 1 | 2008 |
| Gynecologic Oncology Group | Academic/Hospital | 3 | 0 | 1 | 2002 |
| Mayo Clinic | Academic/Hospital | 3 | 1 | 3 | 2001 |
| Methodist Cancer Center, Houston, Texas | Academic/Hospital | 3 | 2 | 1 | 2008 |
| National Institutes of Health (NIH) | Government | 3 | 1 | 2 | 2001 |
| Southwest Oncology Group | Academic/Hospital | 3 | 3 | 2 | 2001 |
| University of California, Davis | Academic/Hospital | 3 | 1 | 2 | 2001 |
| Nektar Therapeutics | For profit | 2 | 2 | 1 | 2011 |
| New York University | Academic/Hospital | 2 | 0 | 2 | 2000 |
| NRG Oncology | Academic/Hospital | 2 | 0 | 1 | 2009 |
63 organizations
Page 1 / 4
Marketing (2)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Bristol-Myers Squibb | For profit | NDA | Oct 16, 2007 |
| R-Pharm | For profit | NDA2 | Oct 16, 2007 |