US 2008/0187935 A1 · Homo and Heterodimer Proteins of the Abcg Family, Methods For Detection and Screening Modulators Thereof

Abstract

The invention relates to methods for screening selective modulators of half transporter proteins of the ABCG family, more closely of ABCG1 and ABCG4. In particular the invention relates to methods for determining whether a substance is a selective activator, an inhibitor or a substrate of an ABCG1 or ABCG4 homodimer or of an ABCG1/ABCG4 heterodimer protein, methods for detection of ABCG1 protein in a biological sample, methods for modulating the function of said proteins, and methods for detecting the presence of and/or quantitating ABCG1/ABCG4 heterodimer activity in a biological sample. Moreover, the invention relates to isolated ABCG1/ABCG4 heterodimer proteins and antibodies selective for ABCG1 or ABCG4. The closely related human ABC half-transporters, ABCG1 and ABCG4, have been suggested to play an important role in cellular lipid/sterol regulation. ABCG1 and ABCG4 and mutants thereof have been expressed and studied by the present inventors in whole cells as well as isolated membrane preparations. A large number of compounds have been screened in this system. Co-expression of the ABCG1 and ABCG4 half transporters resulted in heterodimers.

Claims22

Dependent claims

A method for determining whether a substance is a selective activator, a selective inhibitor or a selective substrate of an ABCG1/ABCG4 heterodimer protein, comprising the steps of

providing an ABCG1 homodimer protein, an ABCG4 homodimer protein and the ABCG1/ABCG4 heterodimer protein in active form,
the homodimer proteins and the heterodimer protein are separately contacted with the substance under conditions appropriate for detecting activities of the proteins,
assessing activities of the homodimer proteins and of the heterodimer protein in the presence and in the absence of the substance, wherein
if, in the presence of the substance, the activity of the heterodimer protein is increased whereas the activities of the homodimer proteins are not increased or increased only to a significantly lesser extent, the substance is considered as a selective activator of the ABCG1/ABCG4 heterodimer protein,
if, in the presence of the substance, the activity of the heterodimer protein is decreased whereas the activities of the homodimer proteins are not decreased or decreased only to a significantly lesser extent, the substance is considered as a selective inhibitor of the ABCG1/ABCG4 heterodimer protein,
if the type of activity assessed is transport activity and the substance is transported by said heterodimer protein whereas it is not transported by the homodimer proteins or transported only to a significantly lesser extent, the substance is considered as a selective substrate of the ABCG1/ABCG4 heterodimer protein.

3 more elements

Dependencies are inferred from the claim text.

Homo and Heterodimer Proteins of the Abcg Family, Methods For Detection and Screening Modulators Thereof

Life of this patent

Homo and Heterodimer Proteins of the Abcg Family, Methods For Detection and Screening Modulators Thereof

Life of this patent

Abstract

Claims22