DNA-templated macrocycle library
The present invention provides nucleic acid templates (e.g., including orthogonal codon sets (e.g., codons from orthogonal codon sets depicted in Tables 5 or 7)) for DNA-templated methods of synthesizing, selecting, and amplifying compounds (e.g., polymers and/or small molecules) described herein. Also provided are novel macrocyclic compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, libraries, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing a disease (e.g., a disease associated with aberrant enzyme activity (e.g., aberrant protease and/or kinase activity (e.g., aberrant IDE activity)), impaired insulin signaling, or insulin resistance in a subject (e.g., a subject having diabetes). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit aberrant protease activity (e.g., aberrant IDE activity).
1. A compound of the formula:
or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, polymorph, tautomer, isotopically enriched form, or prodrug thereof,
wherein R is —(CH 2 ) 2 O(CH 2 ) 2 NH 2 .
2. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, polymorph, tautomer, or isotopically enriched form thereof.
3. The compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, tautomer, or isotopically enriched form thereof.
4. The compound of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 .
7. A compound of the formula:
or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, polymorph, tautomer, isotopically enriched form, or prodrug thereof,
wherein R is —(CH 2 ) 2 O(CH 2 ) 2 NH 2 .
8. The compound of claim 7 , or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, polymorph, tautomer, or isotopically enriched form thereof.
9. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, tautomer, or isotopically enriched form thereof.
10. The compound of claim 7 , or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
11. The compound of claim 7 , or a pharmaceutically acceptable salt thereof.
12. The compound of claim 7 .
13. A compound of the formula:
or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, polymorph, tautomer, isotopically enriched form, or prodrug thereof,
wherein R is —(CH 2 ) 2 O(CH 2 ) 2 NH 2 .
14. The compound of claim 13 , or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, polymorph, tautomer, or isotopically enriched form thereof.
15. The compound of claim 13 , or a pharmaceutically acceptable salt, stereoisomer, tautomer, or isotopically enriched form thereof.
16. The compound of claim 13 , or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
17. The compound of claim 13 , or a pharmaceutically acceptable salt thereof.
18. The compound of claim 13 .