motexafin gadolinium
Gadobutrol is a second-generation extracellular non-ionic macrocyclic GBCA that is used in patients undergoing diagnostic contrast-enhanced MRI for visualization of pathological lesions in the CNS and all other body regions or for contrast-enhanced magnetic resonance angiography (MRA) to evaluate perfusion and flow-related abnormalities. It is a non-ionic, paramagnetic complex consisting of gadolinium (Gd3+) chelated with the macrocyclic compound dihydroxy-hydroxymethylpropyl-tetraazacyclododecane-triacetic acid (butrol). Gadavist (the trade name of gadobutrol) was approved by FDA in 2011 for intravenous use in diagnostic MRI in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. Application of gadobutrol in humans, up to a dose of 0.5 mmol/kg was shown to be well tolerated. Following intravenous administration, gadobutrol may increase MRI sensitivity for the detection of tumors and inflammatory and demyelinating diseases of the central nervous system which are associated with areas with blood-brain barrier defects due to altered perfusion or an enlarged extracellular space. Gadobutrol is not metabolized. It is eliminated in an unchanged form via the kidneys; extra-renal elimination is negligible. Side effects include headache, nausea, abnormal taste and feeling hot. — NCATS
Clinical trial activity
79 trials · 62 clinical orgs · 0 marketing orgs
Earliest trial started Jul 1, 1998 (NCT00003409)
Timeline
Indications
Approved for
Studied for
- Adenocarcinoma · Phase 2
- Allergy and Immunology · Phase 4
- Astrocytoma · Phase 1
- Bile Duct Neoplasms · Phase 1
- Brain Injuries, Traumatic · Phase 2
- Brain Neoplasms · Phase 3
- Breast Neoplasms · Phase 2
- Carcinoma, Bronchogenic · Phase 1
- Carcinoma, Non-Small-Cell Lung · Phase 3
- Carcinoma, Renal Cell · Phase 2
- Central Nervous System Neoplasms · Phase 2
- Colorectal Neoplasms · Phase 2
- Coronary Artery Disease · Phase 2/Phase 3
- Cranial Nerve Diseases · Phase 2
- Cystic Fibrosis · Phase 2
- Diffuse Intrinsic Pontine Glioma · Phase 1
- Drug-Related Side Effects and Adverse Reactions · Early Phase 1
- Dystonia · Phase 1/Phase 2
- Elbow · Phase 1/Phase 2
- Electronic Nicotine Delivery Systems · Phase 1
- Gallbladder Neoplasms · Phase 1
- Gastrointestinal Neoplasms · Phase 2
- Glioblastoma · Phase 1/Phase 2
- Glioma · Phase 2
- Gliosarcoma · Phase 1/Phase 2
- Graft Rejection · Phase 4
- Head and Neck Neoplasms · Phase 1
- Heart Transplantation · Phase 4
- Intestinal Neoplasms · Phase 1
- Kidney Neoplasms · Phase 2
- Laryngeal Neoplasms · Phase 1
- Leiomyosarcoma · Phase 2
- Leukemia · Phase 2
- Leukemia, Lymphocytic, Chronic, B-Cell · Phase 2
- Leukemia, Myeloid, Acute · Phase 1
- Lung Neoplasms · Phase 2
- Lymphoma · Phase 2
- Lymphoma, Non-Hodgkin · Phase 2
- Melanoma · Phase 2
- Meniere Disease · Phase 4
- Migraine Disorders · Phase 1/Phase 2
- Multiple Myeloma · Phase 2
- Myelodysplastic-Myeloproliferative Diseases · Phase 1
- Myeloproliferative Disorders · Phase 1
- Myocardial Ischemia · Phase 2/Phase 3
- Nanoparticles · Phase 2
- Neoplasm Metastasis · Phase 3
- Neoplasms · Phase 3
- Nephrogenic Fibrosing Dermopathy · Phase 2/Phase 3
- Oligodendroglioma · Phase 1
- Oropharyngeal Neoplasms · Phase 1
- Ovarian Neoplasms · Phase 1
- Pancreatic Neoplasms · Phase 1
- Primary Immunodeficiency Diseases · Phase 1/Phase 2
- Prostatic Neoplasms · Phase 2
- Psoriasis · Phase 1/Phase 2
- Pulmonary Disease, Chronic Obstructive · Phase 1
- Pulmonary Embolism · Phase 4
- Radiation Oncology · Phase 2
- Radiosurgery · Phase 2
- Renal Insufficiency · Phase 2/Phase 3
- Small Cell Lung Carcinoma · Phase 2
- Squamous Cell Carcinoma of Head and Neck · Phase 1/Phase 2
- Stereotaxic Techniques · Phase 2
- Stroke · Phase 1/Phase 2
- Urogenital Neoplasms · Phase 2
- Urologic Neoplasms · Phase 2
Mechanism of action
- Thioredoxin reductase 1INHIBITOR
TXNRD1 inhibitor
It inhibits thioredoxin reductase 1 (TrxR1) disulfide reductase activity and induces an NADPH oxidase activity in TrxR1, generating ROS such as superoxide and hydrogen peroxide.
Ribonucleoside-diphosphate reductase RR1 inhibitor
Inhibition of ribonucleotide reductase will block DNA synthesis and repair and cellular growth.
- Unspecified targetOTHER
Diagnostic (when bound to a chelating agent)
Chemistry & pharmacology
SMILES
[Gd+3]- Mol. weight
- 157.25 g/mol
- Chirality
- Achiral Molecule
- Inorganic
- Yes
- Polymer
- No
Oral
No
Parenteral
No
Topical
No
Sources
- WikipediaGadolinium ↗
- NCATSAZV954TZ9N ↗
- ChEMBLCHEMBL3544910 ↗
- ChEMBLCHEMBL1232993 ↗
- WikipediaMotexafin gadolinium ↗
Also known as
- api-gp3
- fp-gp1
- gadolinium
- gadolinium
- gadolinium
- gadolinium texaphyrin
- gadolinium texaphyrin
- gadolinium texaphyrin
- gadolinium texaphyrin
- gadolinium texaphyrin complex
- gd(iii) texaphyrin
- gd-tex
- gd-tex
- gd texaphyrin
- gd texaphyrin
- motexafin gadolinium
- motexafin gadolinium
- motexafin gadolinium
- motexafin gadolinium
- motexafin gadolinium
- moxtezafin gadolinium
- pci-0120
- pci-0120
- pci-0120
- xcytrin
- xcytrin
- xcytrin
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT05692635 | Phase 2 | Aug 30, 2023 | National Cancer Institute (NCI), Wake Forest University |
| NCT05390021 | N/A | Oct 31, 2022 | Harvard University |
| NCT04899908 | Phase 2 | Sep 15, 2021 | Harvard University, NH TherAguix SAS |
| NCT04727242 | Phase 2 | Jan 28, 2021 | Stanford University |
| NCT04474353 | Phase 1 | Nov 30, 2020 | NovoCure Ltd., Stanford University |
| NCT04340180 | Phase 1 | Jun 30, 2020 | Bracco, University of Alabama, Birmingham |
| NCT04264143 | Phase 1 | Apr 30, 2020 | Columbia University, Midatech Pharma |
| NCT04058132 | Phase 2 | Aug 9, 2019 | Uniformed Services University of the Health Sciences, United States Army |
| NCT03565367 | Phase 1 | Nov 14, 2018 | Stanford University |
| NCT03154996 | Phase 1 | Jan 18, 2018 | Columbia University, National Cancer Institute (NCI) |
| NCT03270059 | Phase 2 | Oct 6, 2017 | Celgene, OHSU Knight Cancer Institute, Oregon Health and Science University |
| NCT02234375 | Phase 4 | Jul 1, 2017 | Harvard University |
| NCT03067467 | Early Phase 1 (Phase 1) | May 1, 2017 | The University of Texas, Dallas |
| NCT02783768 | Phase 1 | Mar 1, 2017 | Columbia University |
| NCT02163005 | Phase 4 | Dec 1, 2016 | Harvard University |
| NCT02390635 | Phase 1 | May 1, 2016 | General Electric, University of Texas at Houston |
| NCT02826343 | Early Phase 1 (Phase 1) | May 1, 2016 | National Institutes of Health (NIH), University of Virginia |
| NCT02530931 | Phase 4 | Mar 1, 2016 | Guerbet, University of Grenoble |
| NCT02590497 | N/A | Mar 1, 2016 | Ohio State University |
| NCT02112097 | Phase 1/Phase 2 (Phase 2) | Jan 1, 2016 | ASIS Corporation, AUTOMATIC SUBDERMAL INJECTOR SYSTEM, INC |
Organizations
Research & Development (62)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| National Cancer Institute (NCI) | Government | 24 | 6 | 3 | 1998 |
| Pharmacyclics | For profit | 19 | 17 | 3 | 1998 |
| Stanford University | Academic/Hospital | 6 | 5 | 4 | 2007 |
| ASIS Corporation | For profit | 5 | 5 | 1 | 2016 |
| Northwestern University | Academic/Hospital | 5 | 3 | 3 | 2003 |
| Oregon Health and Science University | Academic/Hospital | 5 | 4 | 2 | 2004 |
| AUTOMATIC SUBDERMAL INJECTOR SYSTEM, INC | Academic/Hospital | 4 | 0 | 1 | 2016 |
| Harvard University | Academic/Hospital | 4 | 4 | 3 | 2016 |
| Columbia University | Academic/Hospital | 3 | 3 | 1 | 2017 |
| Ohio State University | Academic/Hospital | 3 | 1 | 2 | 1999 |
| University of Pennsylvania | Academic/Hospital | 3 | 2 | 2 | 1999 |
| University of Wisconsin | Academic/Hospital | 3 | 1 | 2 | 2002 |
| American College of Radiology | Academic/Hospital | 2 | 2 | 1 | 2010 |
| Astellas | For profit | 2 | 0 | 2 | 2010 |
| Johns Hopkins University | Academic/Hospital | 2 | 2 | 1 | 1999 |
| Mayo Clinic | Academic/Hospital | 2 | 0 | 1 | 2004 |
| University of California, Los Angeles | Academic/Hospital | 2 | 2 | 1 | 1998 |
| University of Pittsburgh | Academic/Hospital | 2 | 1 | 1 | 1998 |
| University of Rochester | Academic/Hospital | 2 | 0 | 2 | 2006 |
| University of South Florida | Academic/Hospital | 2 | 0 | 1 | 1999 |