Ko134 - BCRP Specific Inhibitor
SOLVO Biotechnology is introducing Ko134 for ABCG2/BCRP membrane transporter inhibition studies.
Ko134, the tetracyclic fumitremorgin C (FTC) analog, is a highly potent and specific inhibitor of the ABCG2 (BCRP) multidrug transporter protein. Our data show that Ko-134 inhibits BCRP with IC50 0,070 µM and it inhibits P-gp at IC50 > 1 µM. Contrarily, GF120918 - a model P-gp inhibitor - more potently inhibits P-gp (IC50=0.132) than BCRP (IC50=7.906). Additional data are published by Allen et al, 2002 (1).
| P-gp IC50 (µM) | BCRP IC50 (µM) | |
| Ko134 | >1 | 0.070 |
| GF120918 | 0.132 | 7.906 |
Due to its non-toxic property at its effective concentrations both in vivo and in vitro, Ko134 is an excellent laboratory reagent.
Figure 1 Inhibitory effect of Ko134 on Hoechst 33342 (BCRP substrate)
efflux in a fluorescent whole cell based assay.
Figure 2 Inhibition of the vanadate sensitive ATPase activity of
SB-BCRP-Sf9 preparations by Ko134
Figure 3 Inhibition of the vanadate sensitive ATPase activity of
SB-BCRP-M preparations by Ko134
Figure 4 Ko134 enhanced SN-38 (BCRP substrate anticancer agent)
cytotoxicity in BCRP expressing P388 cells at various concentrations
Reference:
1. John D. Allen, Arnold van Loevezijn, Jeany M. Lakhai, Martin van der Valk,Olaf van Tellingen, Glen Reid, Jan H. M. Schellens,Gerrit-Jan Koomen, and Alfred H. Schinkel (2002) Molecular Cancer Therapeutics Vol. 1, 417-425
2. Glavinas H., et al., ABCG2 (breast cancer resistance protein/mitoxantrone resistance-associated protein) ATPase assay: a useful tool to detect drug-transporter interactions. Drug Metab Dispos. 35(9):1533-42, (2007)
3. Pál A., et al., Cholesterol potentiates ABCG2 activity in a heterologous expression system: improved in vitro model to study function of human ABCG2. J. Pharmaco.l Exp. Ther. 321(3):1085-94, (2007).
4. Van Loevezijn, A., et al., Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines. Bioorg. Med. Chem. Lett. 11, 29-32, (2001)
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