921939

(S,R,S)-AHPC-pyrimidine-piperazine-PEG₁-NH₂ hydrochloride

• Synonym(s): 5-{4-[2-(2-Aminoethoxy)ethyl]piperazin-1-yl}-N-[(2R)-1-[(2R,4S)-4-hydroxy-2-({[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]pyrimidine-2-carboxamide hydrochloride, Crosslinker−E3 Ligase ligand conjugate, Protein degrader building block for PROTAC^® research, Template for synthesis of targeted protein degrader, VH032 conjugate
• Empirical Formula (Hill Notation): C₃₅H₄₉N₉O₅S · xHCl
• Molecular Weight: 707.89 (free base basis)
• NACRES: NA.22

Properties

• ligand: VH032
• Quality Level: 100
• form: solid
• reaction suitability: reactivity: carboxyl reactive; reagent type: ligand-linker conjugate
• functional group: amine
• storage temp.: 2-8°C
• SMILES string: O=C([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(C2=NC=C(C=N2)N3CCN(CC3)CCOCCN)=O)=O)O)NCC4=CC=C(C=C4)C5=C(N=CS5)C.[xHCl]

Description

Application

Protein degrader building block (S,R,S)-AHPC-pyrimidine-piperazine-PEG₁-NH₂ hydrochloride enables the synthesis of molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This conjugate contains a von Hippel–Lindau (VHL)-recruiting ligand, a rigid linker, and a pendant amine for reactivity with a carboxylic acid on the target ligand. Because even slight alterations in ligands and crosslinkers can affect ternary complex formation between the target, E3 ligase, and PROTAC, many analogs are prepared to screen for optimal target degradation. When used with other protein degrader building blocks with a terminal amine, parallel synthesis can be used to more quickly generate PROTAC libraries that feature variation in crosslinker length, composition, and E3 ligase ligand.

Other Notes

Technology Spotlight: Degrader Building Blocks for Targeted Protein Degradation

Portal: Building PROTAC^® Degraders for Targeted Protein Degradation

Targeted Protein Degradation by Small Molecules

Small-Molecule PROTACS: New Approaches to Protein Degradation

Targeted Protein Degradation: from Chemical Biology to Drug Discovery

Impact of linker length on the activity of PROTACs

Legal Information

PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable