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

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

  • Oncotarget. 2014 Dec 15;5(23):11957-70. doi: 10.18632/oncotarget.2566.
Léa Payen 1,  Mylène Honorat 2,  Jérôme Guitton 3,  Charlotte Gauthier 4,  Charlotte Bouard 5,  Florine Lecerf-Schmidt 6,  Basile Peres 6,  Raphaël Terreux 7,  Héloïse Gervot 5,  Catherine Rioufol 8,  Ahcène Boumendjel 6,  Alain Puisieux 5,  Attilio Di Pietro 4
Affiliations

Affiliations

  • 1 Institut 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.
  • 2 Institut 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. Equipe labellisée Ligue 2014, BMSSI UMR 5086 CNRS-Université Lyon 1, IBCP, Lyon 69373, France.
  • 3 Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université Lyon 1, Lyon 69373, France. EA 3738, Laboratoire de Ciblage Thérapeutique en Cancérologie, Centre Hospitalier Lyon-Sud, Pierre Bénite, France. Hospices Civils of Lyon, Laboratoire de Biochimie de Lyon Sud (CBS), Lyon, France.
  • 4 Equipe labellisée Ligue 2014, BMSSI UMR 5086 CNRS-Université Lyon 1, IBCP, Lyon 69373, France.
  • 5 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.
  • 6 Univ. Grenoble Alpes/CNRS, DPM UMR 5063, F-38041 Grenoble, France.
  • 7 Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université Lyon 1, Lyon 69373, France. Equipe labellisée Ligue 2014, BMSSI UMR 5086 CNRS-Université Lyon 1, IBCP, Lyon 69373, France.
  • 8 Hospices Civils of Lyon, Laboratoire de Biochimie de Lyon Sud (CBS), Lyon, France.
PMID: 25474134 DOI: 10.18632/oncotarget.2566
Abstract

ABCG2 is responsible for the multidrug resistance (MDR) phenotype, and strongly modulates Cancer outcomes. Its high expression at a number of physiological barriers, including blood-brain and intestinal barriers, impacts on drug pharmacokinetics parameters. We characterized MBL-II-141, a specific and potent ABCG2 inhibitor. Combination of 10 mg/kg MBL-II-141 with the Anticancer agent CPT-11 completely blocked the growth of 90% freshly implanted ABCG2-positive tumors. Moreover, the same combination slowed the growth of already established tumors. As required for preclinical development, we defined the main pharmacokinetics parameters of MBL-II-141 and its influence on the kinetics of CPT-11 and its active metabolite SN-38 in mice. MBL-II-141 distribution into the brain occurred at a low, but detectable, level. Interestingly, preliminary data suggested that MBL-II-141 is well tolerated (at 50 mg/kg) and absorbed upon force-feeding. MBL-II-141 induced a potent sensitization of ABCG2-positive xenografts to CPT-11 through in vivo ABCG2 inhibition. MBL-II-141 strongly increased CPT-11 levels in the brain, and therefore would be a valuable agent to improve drug distribution into the brain to efficiently treat aggressive gliomas. Safety and Other pharmacological data strongly support the reglementary preclinical development of MBL-II-141.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-17648
    ABCG2抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z