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Merck

Small-Molecule PROTACS: New Approaches to Protein Degradation.

Angewandte Chemie (International ed. in English) (2016-01-13)
Momar Toure, Craig M Crews
ABSTRACT

The current inhibitor-based approach to therapeutics has inherent limitations owing to its occupancy-based model: 1) there is a need to maintain high systemic exposure to ensure sufficient in vivo inhibition, 2) high in vivo concentrations bring potential for off-target side effects, and 3) there is a need to bind to an active site, thus limiting the drug target space. As an alternative, induced protein degradation lacks these limitations. Based on an event-driven model, this approach offers a novel catalytic mechanism to irreversibly inhibit protein function by targeting protein destruction through recruitment to the cellular quality control machinery. Prior protein degrading strategies have lacked therapeutic potential. However, recent reports of small-molecule-based proteolysis-targeting chimeras (PROTACs) have demonstrated that this technology can effectively decrease the cellular levels of several protein classes.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Pomalidomide-C5-phosphoramidite
Sigma-Aldrich
Thalidomide-O-amido-C8-NH2 trifluoroacetate, ≥95.0%
Sigma-Aldrich
(S,R,S)-AHPC-CO-PEG4-C2-acid, ≥95%
Sigma-Aldrich
Pomalidomide-piperidine-carboxylic acid, ≥95%
Sigma-Aldrich
CCW16-C9-BocNH, ≥95%
Sigma-Aldrich
Pomalidomide-PEG4-NH2 hydrochloride, ≥95%
Sigma-Aldrich
3-Pyridinecarboxylic acid, 6-[4-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]-1-piperazinyl]-, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-PEG6-Azide, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-PEG6-NH2 hydrochloride, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-Me-C5-COOH, ≥95%
Sigma-Aldrich
Pomalidomide-PEG3-OH, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-CO-PEG1-C2-acid, ≥95%
Sigma-Aldrich
Pomalidomide-PEG6-butyl CO2H, ≥95%
Sigma-Aldrich
Pomalidomide-PEG5-Alkyne, ≥95%
Sigma-Aldrich
Pomalidomide-PEG2-C2-azide, ≥95%
Sigma-Aldrich
2,7-Diazaspiro[3.5]nonane-7-acetic acid, 2-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]-, ≥95%
Sigma-Aldrich
Pomalidomide-C2-NH2 hydrochloride, ≥95%
Sigma-Aldrich
Pomalidomide-piperazine, ≥ 95.0%
Sigma-Aldrich
VH 032 amide-alkyl C5-acid, ≥95%
Sigma-Aldrich
Pomalidomide-2,6-diazaspiro[3.3]heptane, ≥95.0%
Sigma-Aldrich
CCW16-C6-BocNH
Sigma-Aldrich
CCW16-PEG1-BocNH
Sigma-Aldrich
1-Piperazinecarboxylic acid, 4-(4-piperidinyl)-, 1,1-dimethylethyl ester, ≥98%
Sigma-Aldrich
VH032-OH, ≥95%
Sigma-Aldrich
4-(Aminoethyl)-1-N-Boc-piperidine, ≥95.0%
Sigma-Aldrich
(S,R,S)-AHPC-alkyne-piperidine hydrochloride
Sigma-Aldrich
Pomalidomide-C9-NH2 hydrochloride
Sigma-Aldrich
Pomalidomide-piperazine-propanoic acid, ≥95.0%
Sigma-Aldrich
C5 Lenalidomide-piperazine-pyridine-alkyne-NH2 hydrochloride, ≥95%
Sigma-Aldrich
Pomalidomide-PEG4-Azide, ≥95%