You are viewing a version of a model that has been updated. To access the latest version, and a more detailed display please go here.

DDMODEL00000127: Bueno_PreclinicalBiomarkerTGI

  public model
Short description:
Preclinical Biomarker/tumor growth inhibition model for targeted agents The model integrates the (i) pharmacokinetics drug properties, (ii) drug effect on biomarker turnover, (iii) propagation of the inhibitory tumor growth signal resulted from the biomarker effects, and (iv) tumor growth dynamics.
PharmML (0.6.1)
  • Semi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299, a new type I receptor TGF-beta kinase antagonist, in mice.
  • Bueno L, de Alwis DP, Pitou C, Yingling J, Lahn M, Glatt S, Trocóniz IF
  • European journal of cancer (Oxford, England : 1990), 1/2008, Volume 44, Issue 1, pages: 142-150
  • Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain.
  • Human xenografts Calu6 (non-small cell lung cancer) and MX1 (breast cancer) were implanted subcutaneously in nude mice and LY2157299, a new type I receptor TGF-beta kinase antagonist, was administered orally. Plasma levels of LY2157299, percentage of phosphorylated Smad2,3 (pSmad) in tumour, and tumour size were used to establish a semi-mechanistic pharmacokinetic/pharmacodynamic model. An indirect response model was used to relate plasma concentrations with pSmad. The model predicts complete inhibition of pSmad and rapid turnover rates [t(1/2) (min)=18.6 (Calu6) and 32.0 (MX1)]. Tumour growth inhibition was linked to pSmad using two signal transduction compartments characterised by a mean signal propagation time with estimated values of 6.17 and 28.7 days for Calu6 and MX1, respectively. The model provides a tool to generate experimental hypothesis to gain insights into the mechanisms of signal transduction associated to the TGF-beta membrane receptor type I.
Niklas Hartung
Annotations are correct.
This model is not certified.
  • Model owner: Niklas Hartung
  • Submitted: Dec 15, 2015 7:30:52 PM
  • Last Modified: Jul 15, 2016 10:19:49 AM
Revisions
  • Version: 10 public model Download this version
    • Submitted on: Jul 15, 2016 10:19:49 AM
    • Submitted by: Niklas Hartung
    • With comment: Edited model metadata online.
  • Version: 7 public model Download this version
    • Submitted on: May 20, 2016 2:07:25 PM
    • Submitted by: Niklas Hartung
    • With comment: Model revised without commit message
  • Version: 4 public model Download this version
    • Submitted on: Dec 15, 2015 7:30:52 PM
    • Submitted by: Niklas Hartung
    • With comment: Edited model metadata online.
 
Help