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US 11,293,927 B2Granted
Screening methods for PARP modulators
AssigneeRibon Therapeutics, Inc.
InventorsTimothy J. N. Wigle, Danielle J. Blackwell, Kevin Wayne Kuntz, Melissa Marie Vasbinder, Laurie B. Schenkel, Kerren Kalai Swinger
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Abstract
The present disclosure is related to methods of identifying Poly(ADP-ribose) polymerases (PARP) inhibitors, and the methods of using PARP probes.
Claims14
A method of identifying an inhibitor for Poly (ADP-ribose) polymerase (PARP), the method comprising:
- combining (i) a polypeptide comprising a PARP catalytic domain wherein the polypeptide is labeled with a donor fluorophore, (ii) a PARP probe, wherein the PARP probe is labeled with an acceptor fluorophore or an affinity tag, and (iii) a test compound,
- wherein if the PARP probe is labeled with an affinity tag then an acceptor fluorophore is attached to a molecule that binds to the affinity tag and the molecule is combined with (i)-(iii);
- exposing the donor fluorophore to excitation light;
- measuring a signal produced by the acceptor fluorophore;
- and
- identifying the test compound as an inhibitor for PARP based on the signal produced by the acceptor fluorophore;
- wherein the PARP probe has a structure according to Formula (I):
- or a salt thereof,
- wherein:
- L is a linking group having 5-30 spacer atoms selected from C, N, O, and S connecting the N atom of the piperidinyl group of Formula (I) with group A;
- and
- A is the acceptor fluorophore or the affinity tag.
9 more elements
A method of identifying an inhibitor for Poly (ADP-ribose) polymerase (PARP), the method comprising:
- combining (i) a polypeptide comprising a PARP catalytic domain, wherein the polypeptide is labeled with an acceptor fluorophore;
- (ii) a PARP probe, wherein the PARP probe is labeled with a donor fluorophore or an affinity tag, and (iii) a test compound,
- wherein if the PARP probe is labeled with an affinity tag then a donor fluorophore is attached to a molecule that binds to the affinity tag and the molecule is combined with (i)-(iii);
- exposing the donor fluorophore to excitation light;
- measuring a signal produced by the acceptor fluorophore in the presence of a test compound;
- and
- identifying the test compound as an inhibitor for PARP based on the signal produced by the acceptor fluorophore;
- wherein the PARP probe has a structure according to Formula (I):
- or a salt thereof,
- wherein:
- L is a linking group having 5-30 spacer atoms selected from C, N, O, and S connecting the N atom of the piperidinyl group of Formula (I) with group A;
- and
- A is the acceptor fluorophore or the affinity tag.
10 more elements
Dependencies are inferred from the claim text.