2. Academic Validation
  3. Synthesis of a new inhibitor of breast cancer resistance protein with significantly improved pharmacokinetic profiles

Synthesis of a new inhibitor of breast cancer resistance protein with significantly improved pharmacokinetic profiles

  • Bioorg Med Chem Lett. 2016 Jan 15;26(2):551-555. doi: 10.1016/j.bmcl.2015.11.077.
Yuexian Li 1,  Jiyeon Woo 2,  Jessica Chmielecki 3,  Cindy Q Xia 4,  Mingxiang Liao 4,  Bei-Ching Chuang 4,  Johnny J Yang 4,  Miao Y Guan 4,  Mihaela Plesescu 4,  Shimoga R Prakash 4
Affiliations

Affiliations

  • 1 Department of Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., 35 Landsdowne Street, Cambridge, MA 02139, USA. Electronic address: yuexianfrank.li@takeda.com.
  • 2 Boston University, 881 Commonwealth Avenue, Boston, MA 02215, USA.
  • 3 Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
  • 4 Department of Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., 35 Landsdowne Street, Cambridge, MA 02139, USA.
PMID: 26642765 DOI: 10.1016/j.bmcl.2015.11.077
Abstract

The design, synthesis, in vitro inhibitory potency, and pharmacokinetic (PK) profiles of Ko143 analogs are described. Compared to commonly used Ko143, the new breast Cancer resistance protein (BCRP) inhibitor (compound A) showed the same potency and a significantly improved PK profile in rats (lower clearance [1.54L/h/kg] and higher bioavailability [123%]). Ko143 on the other hand suffers from poor bioavailability. Compared to Ko143, compound A would be a useful probe for delineating the role of BCRP during in vivo studies in Animals.

Keywords

BCRP; Compound A; Inhibitors; Ko134; Ko143; PK profiles.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100390
    99.25%, BCRP抑制剂
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