2. Academic Validation
  3. In vitro and in vivo reversal of MDR1-mediated multidrug resistance by KT-5720: implications on hematological malignancies

In vitro and in vivo reversal of MDR1-mediated multidrug resistance by KT-5720: implications on hematological malignancies

  • Leuk Res. 2006 Sep;30(9):1151-8. doi: 10.1016/j.leukres.2006.02.016.
Hanan Galski 1,  Hamutal Sivan,  Philip Lazarovici,  Arnon Nagler
Affiliations

Affiliation

  • 1 Laboratory of Molecular Immunobiology, Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel. hgalski@sheba.health.gov.il
PMID: 16542724 DOI: 10.1016/j.leukres.2006.02.016
Abstract

Multidrug resistance (MDR) due to over-expression of the MDR1 (ABCB1) gene and its P-glycoprotein (Pgp) product is an obstacle in the treatment of hematological malignancies. In this study, we have evaluated the potency of KT-5720 to reverse Pgp-dependent MDR in vitro and in vivo. KT-5720 (but not its close derivatives, K252a and K252b) reversed multidrug resistance of LM1/MDR cell line at non-toxic concentrations and increased accumulation of rhodamine 123 (Rh123). KT-5720 significantly reversed MDR1-dependent resistance of primary malignant cells from patients with chronic myelogenous leukemia in blast crisis (CML-BC) and advanced multiple myeloma (MM). Moreover, KT-5720 (at 5 mg/kg) sensitized the bone marrow of MDR1 transgenic mice model towards daunorubicin (at 8 mg/kg) without general toxic effects. Therefore, KT-5720 can be considered as candidate for combination therapy in various hematological malignancies where Pgp activity is a major impediment for cure.

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