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Gadopiclenol

PubChem CID
16223405
Structure
Gadopiclenol_small.png
Molecular Formula
Synonyms
  • Gadopiclenol
  • UNII-S276568KOY
  • Gadopiclenol [USAN]
  • S276568KOY
  • ELUCIREM
Molecular Weight
970.1 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Parent Compound
Dates
  • Create:
    2007-07-23
  • Modify:
    2025-01-18
Description
Gadopiclenol is a gadolinium-based contrast agent (GBCA) based on a pyclen macrocyclic structure. It is indicated for use with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system and the body. In 2006, the use of GBCAs was associated with the development of nephrogenic systemic fibrosis (NSF), a rare disorder characterized by the thickening and hardening of skin and subcutaneous tissues. However, studies revealed that NSF was associated with linear GBCAs, not macrocyclic GBCAs, such as gadopiclenol. Gadopiclenol has high kinetic stability and a high r1 relaxivity, allowing it to be used at lower doses than classic extracellular GBCAs. In September 2022, the use of gadopiclenol was approved by the FDA. The product label includes a black box warning regarding the increased risk for NSF among patients with impaired elimination of the drugs.
Gadopiclenol is a gadolinium-based paramagnetic contrast agent, with potential imaging enhancing activity upon magnetic resonance imaging (MRI). Upon administration of gadopiclenol and placement in a magnetic field, this agent produces a large magnetic moment and creates a large local magnetic field, which can enhance the relaxation rate of nearby protons. This change in proton relaxation dynamics, increases the MRI signal intensity of tissues in which this agent has accumulated; therefore, contrast and visualization of those tissues is enhanced compared to unenhanced MRI.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Gadopiclenol.png

1.2 3D Status

Conformer generation is disallowed since too many atoms, MMFF94s unsupported element, too flexible, mixture or salt, too many undefined stereo centers

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2-[3,9-bis[1-carboxylato-4-(2,3-dihydroxypropylamino)-4-oxobutyl]-3,6,9,15-tetrazabicyclo[9.3.1]pentadeca-1(15),11,13-trien-6-yl]-5-(2,3-dihydroxypropylamino)-5-oxopentanoate;gadolinium(3+)
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C35H57N7O15.Gd/c43-19-24(46)14-36-30(49)7-4-27(33(52)53)40-10-12-41(28(34(54)55)5-8-31(50)37-15-25(47)20-44)17-22-2-1-3-23(39-22)18-42(13-11-40)29(35(56)57)6-9-32(51)38-16-26(48)21-45;/h1-3,24-29,43-48H,4-21H2,(H,36,49)(H,37,50)(H,38,51)(H,52,53)(H,54,55)(H,56,57);/q;+3/p-3
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

GNRQMLROZPOLDG-UHFFFAOYSA-K
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C1CN(CC2=NC(=CC=C2)CN(CCN1C(CCC(=O)NCC(CO)O)C(=O)[O-])C(CCC(=O)NCC(CO)O)C(=O)[O-])C(CCC(=O)NCC(CO)O)C(=O)[O-].[Gd+3]
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C35H54GdN7O15
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

933983-75-6

2.3.2 UNII

2.3.3 DrugBank ID

2.3.4 KEGG ID

2.3.5 NCI Thesaurus Code

2.3.6 RXCUI

2.3.7 Wikidata

2.3.8 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 3,6,9,15-Tetraazabicyclo(9.3.1)pentadeca-1(15),11,13-triene-3,6,9-triacetic acid, alpha, alpha', alpha''-tris(3-((2,3-dihydroxypropyl)amino)-3-oxopropyl)-, gadolinium salt (1:1)
  • Gadolinium 2,2',2''-(3,6,9,15-tetraazabicyclo(9.3.1)pentadeca-1(15),11,13-triene-3,6,9-triyl)tris(5-((2,3-dihydroxypropyl)amino)-5-oxopentanoate)
  • gadopiclenol

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
970.1 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
9
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
19
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
21
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
970.29190 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
970.29190 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
352 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
58
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
1200
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
6
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
2
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Chemical Classes

3.2.1 Drugs

3.2.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Contrast Media; Diagnostic Agents
Human drug -> Active ingredient (GADOPICLENOL)
Human drug -> Prescription
Paediatric drug

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug Indication

Gadopiclenol is indicated in adult and pediatric patients aged 2 years and older for use with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system (brain, spine, and associated tissues) and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system).
Detection and visualization of disorders or lesions with suspected abnormal vascularity in various body regions for diagnostic purposes
Detection and visualisation of areas with disruption of the blood brain barrier and/or abnormal vascularity for diagnostic purposes

6.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Contrast Media; Diagnostic Agents

6.3 FDA Medication Guides

Drug
Active Ingredient
GADOPICLENOL
Form;Route
INJECTABLE;INTRAVENOUS
Company
LIEBEL-FLARSHEIM COMPANY
Date
01/26/2024

6.4 FDA Approved Drugs

6.5 FDA Orange Book

6.6 FDA National Drug Code Directory

6.7 Drug Labels

Drug and label
Active ingredient and drug

6.8 Clinical Trials

6.8.1 ClinicalTrials.gov

6.8.2 EU Clinical Trials Register

6.9 EMA Drug Information

1 of 2
Type
Paediatric investigation
Active Substance
Therapeutic Area
Diagnostic
Drug Form
Solution for injection
Administration Route
Intravenous use
Decision Type
PM: decision on the application for modification of an agreed PIP
Decision Date
2022-08-04
2 of 2
Type
Paediatric investigation
Active Substance
Therapeutic Area
Diagnostic
Drug Form
Solution for injection
Administration Route
Intravenous use
Decision Type
PM: decision on the application for modification of an agreed PIP
Decision Date
2021-04-16

7 Pharmacology and Biochemistry

7.1 Pharmacodynamics

Variations in radiofrequency signal intensity allow the visualization of normal and pathological tissues during magnetic resonance imaging (MRI). These variations occur due to differences in proton density, differences of the spin-lattice or longitudinal relaxation times (T1), or differences in the spin-spin or transverse relaxation time (T2). Gadopiclenol shortens the T1 and T2 relaxation times and allows the visualization of targeted tissues during an MRI. The extent to which a contrast agent can affect the relaxation rate of tissue water (1/T1 or 1/T2) is termed relaxivity (r1 or r2). Gadopiclenol has a high r1 relaxivity compared to other gadolinium-based contrast agents. The use of gadopiclenol is not associated with QT interval prolongation; however, it can increase the risk for nephrogenic systemic fibrosis in patients with impaired elimination of the drugs. The use of gadopiclenol may also cause hypersensitivity reactions and acute kidney injury.

7.2 ATC Code

V - Various

V08 - Contrast media

V08C - Magnetic resonance imaging contrast media

V08CA - Paramagnetic contrast media

V08CA12 - Gadopiclenol

7.3 Absorption, Distribution and Excretion

Absorption
At a dose range between 0.025 mmol/kg and 0.3 mmol/kg (0.5 times to 6 times the recommended dosage), the Cmax and AUCinf of gadopiclenol increases in a dose-proportional manner. At the recommended dose, gadopiclenol has a Cmax of 525 µg/mL and an AUCinf of 569 µg·h/mL. A study that evaluated the pharmacokinetic parameters of gadopiclenol in healthy subjects and patients with brain lesions did not detect significant differences between the two groups.
Route of Elimination
Gadopiclenol is mainly excreted in urine by glomerular filtration. Within 48 hours after administration, approximately 98% of the gadopiclenol dose was recovered in urine.
Volume of Distribution
At steady state, the mean volume of distribution of gadopiclenol is 13 L.
Clearance
Gadopiclenol has a total body clearance of 100 mL/min and a renal clearance of 81 mL/min.

7.4 Metabolism / Metabolites

Gadopiclenol is not metabolized and is eliminated unchanged.

7.5 Biological Half-Life

Gadopiclenol has a mean elimination half-life of is 1.5 hours.

7.6 Mechanism of Action

Gadopiclenol is a macrocyclic non-ionic complex of gadolinium and a paramagnetic molecule that develops a magnetic moment when placed in a magnetic field. The magnetic moment alters the relaxation rates of water protons in its vicinity in the body. Its use in magnetic resonance imaging (MRI) allows to selectively increase contrast in tissues where gadopiclenol accumulates.

8 Use and Manufacturing

8.1 Uses

8.1.1 Use Classification

Human Drugs -> EU pediatric investigation plans
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9 Toxicity

9.1 Toxicological Information

9.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Guidelines developed by several professional organizations state that breastfeeding need not be disrupted after a nursing mother receives a gadolinium-containing contrast medium. However, because there is no published experience with gadopiclenol during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

9.1.2 Protein Binding

At clinically relevant concentrations, the protein binding of gadopiclenol is ≤ 1.8%.

10 Literature

10.1 NLM Curated PubMed Citations

10.2 Chemical Co-Occurrences in Literature

10.3 Chemical-Gene Co-Occurrences in Literature

10.4 Chemical-Disease Co-Occurrences in Literature

11 Patents

11.1 Depositor-Supplied Patent Identifiers

11.2 FDA Orange Book Patents

11.3 Chemical Co-Occurrences in Patents

11.4 Chemical-Disease Co-Occurrences in Patents

12 Classification

12.1 MeSH Tree

12.2 NCI Thesaurus Tree

12.3 KEGG: ATC

12.4 WHO ATC Classification System

12.5 ChemIDplus

13 Information Sources

  1. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  2. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  3. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  4. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  5. DailyMed
  6. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  7. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  8. Drugs and Lactation Database (LactMed)
  9. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. EU Clinical Trials Register
  11. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  12. FDA Medication Guides
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  13. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
  14. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  15. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  16. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  17. Wikidata
  18. Wikipedia
  19. PubChem
  20. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
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