Methods and compositions for screening and identification of splicing modulators
AssigneeSkyhawk Therapeutics, Inc.
InventorsKATHLEEN MCCARTHY, MICHAEL LUZZIO
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Abstract
Provided herein are structure-based screening platforms and methods to identify small molecules that can bind polynucleotides and/or complexes formed by polynucleotides and proteins. Structure-based screening platforms and methods to characterize interactions of small molecules with polynucleotides and/or with complexes formed by polynucleotides and proteins are also provided herein. Methods and compositions to identify small molecules that can bind polynucleotides and/or polynucleotide-protein complexes involved in RNA splicing are also provided herein.
Claims18
A compound having the structure of Formula (III), or a pharmaceutically acceptable salt or solvate thereof:
- wherein,
- ring A is heteroaryl;
- L1 is —X4-L3-, or -L3-X4—;
- X1 is absent;
- L3 is absent;
- ring B is heteroaryl;
- each RB is halogen;
- each R1 is independently H, C1-C6alkyl or C1-C6fluoroalkyl;
- L2 is —X2-L4-, or -L4-X2—;
- X2 is absent;
- L4 is absent;
- ring C is monocyclic heterocycle, or bicyclic heterocycle;
- each RC is independently selected from halogen, N(R1)2, or C1-C6alkyl;
- ring D is monocyclic heterocycle;
- each RD is independently C1-C6alkyl or C1-C6fluoroalkyl;
- L5 is —X3-L6-, or -L6-X3—;
- X3 is absent;
- L6 is absent;
- n is 0;
- m is 0 or 1;
- q is 0, 1, 2, 3, 4, 5, or 6;
- and
- p is 0 or 1.
A compound having the structure of Formula (XVI), or a pharmaceutically acceptable salt or solvate thereof:
- wherein,
- ring A is a 6-membered heteroaryl;
- L1 is —X1A-L3-X1B—, -L3-X1A—X1B—, or —X1A—X1B-L3-;
- X1A is absent;
- L3 is absent;
- X1B is absent;
- ring B is a bicyclic heterocycle;
- each RB is independently selected from halogen and monocyclic heteroaryl;
- each R1 is independently H, C1-C6alkyl or C1-C6fluoroalkyl;
- L2 is —X2-L4- or -L4-X2—;
- X2 is —O— or —S—;
- L4 is absent;
- ring C is monocyclic heterocycle;
- each RC is independently selected from F, —N(R1)2, and C1-C6alkyl;
- n is 0;
- m is 1 or 2;
- and
- q is 0, 1, 2, 3, 4, 5, or 6.
Dependencies are inferred from the claim text.