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Merck

Targeted Protein Degradation: from Chemical Biology to Drug Discovery.

Cell chemical biology (2017-06-27)
Philipp M Cromm, Craig M Crews
ABSTRACT

Traditional pharmaceutical drug discovery is almost exclusively focused on directly controlling protein activity to cure diseases. Modulators of protein activity, especially inhibitors, are developed and applied at high concentration to achieve maximal effects. Thereby, reduced bioavailability and off-target effects can hamper compound efficacy. Nucleic acid-based strategies that control protein function by affecting expression have emerged as an alternative. However, metabolic stability and broad bioavailability represent development hurdles that remain to be overcome for these approaches. More recently, utilizing the cell's own protein destruction machinery for selective degradation of essential drivers of human disorders has opened up a new and exciting area of drug discovery. Small-molecule-induced proteolysis of selected substrates offers the potential of reaching beyond the limitations of the current pharmaceutical paradigm to expand the druggable target space.

MATERIALS
Product Number
Brand
Product Description

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
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-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-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-piperazine, ≥ 95.0%
Sigma-Aldrich
Pomalidomide-2,6-diazaspiro[3.3]heptane, ≥95.0%
Sigma-Aldrich
1-Piperazinecarboxylic acid, 4-(4-piperidinyl)-, 1,1-dimethylethyl ester, ≥98%
Sigma-Aldrich
4-(Aminoethyl)-1-N-Boc-piperidine, ≥95.0%
Sigma-Aldrich
(S,R,S)-AHPC-alkyne-piperidine hydrochloride
Sigma-Aldrich
Pomalidomide-PEG4-Azide, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-PEG1-Alkyne, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-PEG2-Alkyne, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-PEG4-Alkyne
Sigma-Aldrich
(S,R,S)-AHPC-PEG5-Alkyne
Sigma-Aldrich
(S,R,S)-AHPC-piperazine-pyridine-alkyne-NH2 hydrochloride
Sigma-Aldrich
(S,R,S)-AHPC-acetamido-O-PEG4-C1-acid, ≥95%
Sigma-Aldrich
Propanoic acid, 3-[2-[2-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]amino]ethoxy]ethoxy]ethoxy]-, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-C9-NH2 hydrochloride, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-pentanoic-acid, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-PEG2-butyl CO2H, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-PEG1-NH2 hydrochloride, ≥95%
Sigma-Aldrich
Pomalidomide-PEG4-NH2 hydrochloride, ≥95%
Sigma-Aldrich
(S,R,S)-AHPC-C6-PEG3-butyl amine hydrochloride, ≥95%