Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Experimental and Molecular Therapeutics

Abstract 4522: Pharmacokinetic evaluation of a novel anti-angiogenic molecule named JFD-WS in Balb/c mice

Manasa Subbarao, Sivanesan Dhandayuthapani, Mortatha Albassam and Appu Rathinavelu
Manasa Subbarao
Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Plantation, FL;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sivanesan Dhandayuthapani
Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Plantation, FL;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mortatha Albassam
Farquhar College of Arts and Sciences, Nova Southeastern University, Fort Lauderdale, FL.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Appu Rathinavelu
Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Plantation, FL;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM2015-4522 Published August 2015
  • Article
  • Info & Metrics
Loading
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Abstract

JFD is a novel anti-angiogenic compound which mediates its action by blocking Vascular Endothelial Growth Factor Receptors and associated kinase activity, thereby arresting tumor angiogenesis and growth. The original JFD has been modified into a water soluble form (JFD-WS) to increase bioavailability and distribution during the in vivo pre-clinical testing in mouse model. Through both in vitro and in vivo testing, we have confirmed its anti-angiogenic and cytoreductive properties and are currently establishing its pharmacokinetic (PK) properties. The absorption, distribution and elimination of JFD-WS were determined by measuring the plasma and urine concentrations after intraperitoneal (i.p.) and oral administration in Balb/c mice. Following i.p. administration of JFD-WS (100 mg/kg body weight), the plasma samples were collected at 2.5, 5, 10, 15, 30, 60, 120, 1440 mins and the urine samples were collected at 15, 30, 60, 120, 1440 mins. The JFD-WS was extracted using a simple liquid extraction procedure and the concentrations in the plasma and urine were analyzed using HPLC method. Our experiments showed that JFD-WS can reach peak plasma concentration after 15 mins and a maximum elimination in urine was observed after 30 mins of i.p. injection. The compound was undetectable in both plasma and urine after 24 hours. Further analysis of plasma levels of JFD-WS using standard PK parameters has led us to hypothesize that JFD-WS may follow a two compartment kinetic model, according to which the molecule may enter the liver through the portal vein after absorption from the peritoneal cavity. During drug distribution, JFD-WS seems to enter the first compartment, including blood circulation, and then reaches the second compartment i.e., the rest of the body till equilibrium is attained. It is further speculated that the first phase of CYP450 system mediated metabolism may not be very extensive since our compound is in water soluble form. Finally, a majority of the molecule is excreted out by glomerular filtration in urine while a small portion is removed through the feces as well. Derived from an established PK formula, the half-life (t½) of our JFD-WS molecule was found to be around 33 mins. A high volume of distribution calculated for JFD-WS leads us to assume that it may distribute largely in extravascular regions such as muscles and tissues, while a high clearance rate could contribute to the lower toxicity of the compound. This hypothesis is further supported by our observations found in the in vivo systems, wherein JFD-WS is highly effective in causing tumor inhibition with minimal toxicity. Thus, the results of our study confirm that i.p. administration allows for reasonable distribution of JFD-WS to the tumor sites within a shorter duration of time that can produce cytoreductive effect. (The Royal Dames of Cancer Research Inc., Ft. Lauderdale Florida is gratefully acknowledged for their generous financial support).

Citation Format: Manasa Subbarao, Sivanesan Dhandayuthapani, Mortatha Albassam, Appu Rathinavelu. Pharmacokinetic evaluation of a novel anti-angiogenic molecule named JFD-WS in Balb/c mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4522. doi:10.1158/1538-7445.AM2015-4522

  • ©2015 American Association for Cancer Research.
Previous
Back to top
Cancer Research: 75 (15 Supplement)
August 2015
Volume 75, Issue 15 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract 4522: Pharmacokinetic evaluation of a novel anti-angiogenic molecule named JFD-WS in Balb/c mice
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract 4522: Pharmacokinetic evaluation of a novel anti-angiogenic molecule named JFD-WS in Balb/c mice
Manasa Subbarao, Sivanesan Dhandayuthapani, Mortatha Albassam and Appu Rathinavelu
Cancer Res August 1 2015 (75) (15 Supplement) 4522; DOI: 10.1158/1538-7445.AM2015-4522

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract 4522: Pharmacokinetic evaluation of a novel anti-angiogenic molecule named JFD-WS in Balb/c mice
Manasa Subbarao, Sivanesan Dhandayuthapani, Mortatha Albassam and Appu Rathinavelu
Cancer Res August 1 2015 (75) (15 Supplement) 4522; DOI: 10.1158/1538-7445.AM2015-4522
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Experimental and Molecular Therapeutics

  • Abstract SY14-03: Anaplastic lymphoma kinase (ALK): Normal biology and role in hematopoietic malignancies
  • Abstract SY18-01: Targeting the p53-MDM2 interaction for cancer therapy
  • Abstract SSY01-04: Discovery and validation of genome-wide genetic signatures of chemotherapy susceptibility: A translational model
Show more 3

Poster Presentations - Proffered Abstracts

  • Abstract SY14-03: Anaplastic lymphoma kinase (ALK): Normal biology and role in hematopoietic malignancies
  • Abstract SY18-01: Targeting the p53-MDM2 interaction for cancer therapy
  • Abstract SSY01-04: Discovery and validation of genome-wide genetic signatures of chemotherapy susceptibility: A translational model
Show more 3

Poster Presentations - Pharmacokinetics and Pharmacodynamics

  • Abstract 4504: Plasma pharmacokinetics and tumor accumulation in mice of IMGN779, an antibody-drug conjugate for acute myeloid leukemia
  • Abstract 4528: Characterization of changes in passive permeability and drug uptake at the blood-tumor barrier in four preclinical models of brain metastases of breast cancer
  • Abstract 4510: Model-based phase II dose selection of c-Met inhibitor MSC2156119J
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement