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ONT-093 (Ontogen)

Prakash Mistry1, Adrian Folkes

  • 1Xenova Ltd, 957 Buckingham Avenue, Slough, Berkshire, SL1 4NL, UK. prakash_mistry@xenova.co.uk

Current Opinion in Investigational Drugs (London, England : 2000)
|December 13, 2002
PubMed

Insights

ONT-093 is a novel P-glycoprotein pump inhibitor being developed to combat multidrug resistance in cancer chemotherapy. This compound may also improve drug bioavailability and central nervous system penetration for P-glycoprotein substrate drugs.

Area of Science:

  • Pharmacology
  • Oncology
  • Drug Development

Background:

  • Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy, limiting treatment efficacy.
  • P-glycoprotein (P-gp) is a key efflux pump responsible for MDR by extruding chemotherapeutic agents from cancer cells.
  • P-gp also affects the oral bioavailability and central nervous system (CNS) penetration of various drugs.

Purpose of the Study:

  • To evaluate ONT-093, a P-glycoprotein pump inhibitor, for its potential to reverse multidrug resistance in cancer patients.
  • To assess the capacity of ONT-093 to enhance the oral bioavailability of P-glycoprotein substrate drugs.
  • To investigate the potential of ONT-093 to improve CNS penetration of P-glycoprotein substrate drugs.

Main Methods:

  • Preclinical studies involving P-glycoprotein inhibition assays.
  • Pharmacokinetic studies to evaluate oral bioavailability.
  • In vivo models to assess CNS penetration and reversal of multidrug resistance.

Main Results:

  • ONT-093 demonstrated potent inhibition of P-glycoprotein activity.
  • Preliminary data suggests potential for enhanced oral bioavailability of P-gp substrate drugs.
  • Evidence indicates improved CNS penetration of P-gp substrate drugs in relevant models.

Conclusions:

  • ONT-093 shows promise as a P-glycoprotein inhibitor for overcoming cancer multidrug resistance.
  • The compound may offer therapeutic benefits by improving drug delivery and efficacy.
  • Further clinical evaluation is warranted to confirm these findings in patients.

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