Rna degraders and uses thereof
AssigneeArrakis Therapeutics, Inc.
InventorsRobin Prince, Wilnelly Martinez Ortiz, Elias Ndaru, Lee Roberts
Life of this patent
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Abstract
The present invention includes compounds and compositions, and methods of use thereof for modulating an RNA transcript, or a precursor, isoform, fragment, or mutant thereof by degradation of the RNA transcript via recruitment or binding of one or more decay factors (e.g., an RNA binding protein).
Claims60
A compound of Formula B:
- or a pharmaceutically acceptable salt thereof, wherein:
- RNA Binder is a moiety that binds to a target RNA transcript;
- DFL is a Decay Factor-recruiting Ligand;
- and
- -L1- is a bivalent linker group that covalently connects the RNA Binder to the DFL;
- wherein the DFL binds to or recruits a decay factor.
A compound of Formula A:
- or a pharmaceutically acceptable salt thereof, wherein:
- rSM is an RNA-binding small molecule that binds to a target RNA transcript;
- DFL is a Decay Factor-recruiting Ligand;
- and
- -L1- is a bivalent linker group that covalently connects the rSM to the DFL;
- wherein the DFL binds to or recruits a decay factor.
A compound of any of the preceding claims, wherein the decay factor is a protein that binds or interacts with RNA (an RBP) and wherein the interaction of the RBP with the RNA leads to modulation of the target RNA transcript in vivo.
The compound of any one of the preceding claims, wherein the target RNA transcript is an mRNA or a precursor, isoform, unspliced isoform, splicing intermediate, fragment, or mutant thereof.
The compound of any one of the preceding claims, wherein the target RNA transcript is selected from one of those listed in Table C or D;
- or a precursor, isoform, unspliced isoform, splicing intermediate, fragment, or mutant thereof.
The compound of any one of the preceding claims, wherein the rSM is selected from any one of those described in paragraphs under the heading RNA-Binding Small Molecules (rSMs).
The compound of any one of the preceding claims, wherein the rSM is one of those shown in Table 2.
A pharmaceutical composition comprising the compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
A method of modifying the amount of a protein in a cell, the method comprising administering the compound or composition of any of the preceding claims, or a pharmaceutically acceptable salt thereof, that acts on a target RNA transcript or a precursor, isoform, fragment, or mutant thereof, in an amount sufficient to modify the amount of the protein in the cell.
A method of modulating the availability for protein translation of a target RNA transcript or a precursor, isoform, fragment, or mutant thereof, comprising contacting the target RNA transcript or a precursor, isoform, fragment, or mutant thereof with the compound or composition of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, that binds to the target RNA transcript or an isoform, fragment, or mutant thereof.
A method of modulating the translation of a target protein or mutant thereof, comprising contacting a target RNA transcript or a precursor, isoform, fragment, or mutant thereof with the compound or composition of any one of preceding claims, or a pharmaceutically acceptable salt thereof.
A method of decreasing the half-life or increasing degradation of a target RNA transcript or a precursor, isoform, fragment, or mutant thereof, comprising contacting the target RNA transcript or the precursor, isoform, fragment, or mutant thereof with the compound or composition of any one of the preceding claims, or a pharmaceutically acceptable salt thereof.
A method of treating a disease, comprising administering to a subject in need thereof the compound or composition of any one of preceding claims, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.