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Merck

917559

Sigma-Aldrich

(S,R,S)-AHPC-C6-NH2 hydrochloride

≥95%

Synonym(e):

(2S,4R)-1-((S)-2-(7-aminoheptanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride, Crosslinker−E3 ligase ligand conjugate, Protein degrader building block for PROTAC® research, Template for synthesis of targeted protein degrader, VH032 conjugate

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About This Item

Empirische Formel (Hill-System):
C29H43N5O4S · xHCl
CAS-Nummer:
Molekulargewicht:
557.75 (free base basis)

ligand

VH032

Assay

≥95%

Form

(Powder or Crystals or Solid or Chunks)

Eignung der Reaktion

reactivity: carboxyl reactive
reagent type: ligand-linker conjugate

Funktionelle Gruppe

amine

Lagertemp.

2-8°C

SMILES String

CC(N=CS1)=C1C2=CC=C(CNC([C@@H]3C[C@@H](O)CN3C([C@@H](NC(CCCCCCN)=O)C(C)(C)C)=O)=O)C=C2.Cl

Anwendung

Protein degrader building block (S,R,S)-AHPC-C6-NH2 hydrochloride enables the synthesis of molecules for targeted protein degradationand PROTAC (proteolysis-targeting chimeras) technology. This conjugate contains a von Hippel-Lindau (VHL)-recruiting ligand and an alkyl-chain crosslinker with pendant amine for reactivity with an acid on the target warhead. Because even slight alterations in ligands, warheads, 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.

Rechtliche Hinweise

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

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Lagerklassenschlüssel

11 - Combustible Solids

WGK

WGK 3

Flammpunkt (°F)

Not applicable

Flammpunkt (°C)

Not applicable


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Philipp M Cromm et al.
Cell chemical biology, 24(9), 1181-1190 (2017-06-27)
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
Momar Toure et al.
Angewandte Chemie (International ed. in English), 55(6), 1966-1973 (2016-01-13)
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

Artikel

Protein Degrader Building Blocks are a collection of crosslinker-E3 ligand conjugates with a pendant functional group for covalent linkage to a target ligand.

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