Related Experiment Video

Updated: Apr 20, 2026

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
15:04

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation

Published on: January 19, 2019

13.0K

MBL-II-141, a chromone derivative, enhances irinotecan (CPT-11) anticancer efficiency in ABCG2-positive xenografts

Léa Payen1, Mylène Honorat2, Jérôme Guitton3

  • 1Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université Lyon 1, Lyon 69373, France. INSERM UMR-S1052, CNRS UMR 5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon (CRCL), LabEx DEVweCAN, Centre Léon Bérard, Lyon 69373, France. Hospices Civils of Lyon, Laboratoire de Biochimie de Lyon Sud (CBS), Lyon, France.

Oncotarget
|December 5, 2014
PubMed

Insights

MBL-II-141, an ABCG2 inhibitor, combined with CPT-11, blocked 90% of new ABCG2-positive tumors and slowed established ones. This combination enhances CPT-11 brain delivery for aggressive glioma treatment.

Area of Science:

  • Pharmacology
  • Oncology
  • Drug Discovery

Background:

  • ABCG2 transporter mediates multidrug resistance (MDR) and affects cancer patient outcomes.
  • High ABCG2 expression at physiological barriers impacts drug pharmacokinetics.
  • ABCG2 inhibition is a potential strategy to overcome MDR and improve cancer therapy.

Purpose of the Study:

  • To characterize MBL-II-141, a novel ABCG2 inhibitor.
  • To evaluate the efficacy of MBL-II-141 in combination with CPT-11 against ABCG2-positive tumors.
  • To determine the pharmacokinetic profile of MBL-II-141 and its effect on CPT-11/SN-38 kinetics.

Main Methods:

  • In vivo efficacy studies using ABCG2-positive tumor models.
  • Pharmacokinetic analysis of MBL-II-141, CPT-11, and SN-38 in mice.
  • Assessment of MBL-II-141 tolerability and absorption.

Main Results:

  • Combination of MBL-II-141 (10 mg/kg) and CPT-11 completely blocked 90% of freshly implanted ABCG2-positive tumors.
  • The combination also slowed the growth of established tumors.
  • MBL-II-141 increased CPT-11 levels in the brain, indicating improved drug distribution.
  • Preliminary data showed MBL-II-141 is well-tolerated and absorbed upon force-feeding.

Conclusions:

  • MBL-II-141 effectively inhibits ABCG2 in vivo, sensitizing tumors to CPT-11.
  • MBL-II-141 demonstrates potential for enhancing CPT-11 brain penetration.
  • MBL-II-141 warrants further preclinical development for treating aggressive gliomas and other ABCG2-related cancers.

More Related Videos

A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research08:17

A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research

Published on: August 15, 2019

15.7K
Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer06:49

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer

Published on: February 10, 2023

3.1K

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.4K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.2K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
790
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.6K