理化性质和储存条件
| Molecular Weight (MW) | 544.59 |
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| Formula | C24H31F3N4O5S |
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| CAS No. | 1631137-51-3 (TFA salt); |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 10 mM |
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| Water: N/A |
| Ethanol: N/A |
| Chemical Name | (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 2,2,2-trifluoroacetate |
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| Synonyms | Protein degrader 1 TFA; VH032-NH2 TFA; VHL ligand 1 TFA; Protein degrader 1 TFA , VHL-7526 TFA; VHL-7526; VHL7526; VHL 7526 trifluoroacetic acid |
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| SMILES Code | FC(F)(F)C(O)=O.O=C([C@H](C[C@@H](O)C1)N1C([C@@H](N)C(C)(C)C)=O)NCC2=CC=C(C(SC=N3)=C3C)C=C2 |
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实验参考方法
Protein degrader 1 TFA (trifluoroacetic acid salt) is a novel and potent small molecule ligand for VHL (Von Hippel-Lindau), an E3 ligase which has been targeted in many PROTACs (proteolysis-targeting chimeras). Small molecule-induced protein degradation is an attractive strategy for the development of chemical probes. One method for inducing targeted protein degradation involves the use of PROTACs, heterobifunctional molecules that can recruit specific E3 ligases to a desired protein of interest. PROTACs have been successfully used to degrade numerous proteins in cells, but the peptidic E3 ligase ligands used in previous PROTACs have hindered their development into more mature chemical probes or therapeutics.
Small molecule-induced protein degradation is an attractive strategy for the development of chemical probes. One method for inducing targeted protein degradation involves the use of PROTACs, heterobifunctional molecules that can recruit specific E3 ligases to a desired protein of interest. PROTACs have been successfully used to degrade numerous proteins in cells, but the peptidic E3 ligase ligands used in previous PROTACs have hindered their development into more mature chemical probes or therapeutics. We report the design of a novel class of PROTACs that incorporate small molecule VHL ligands to successfully degrade HaloTag7 fusion proteins. These HaloPROTACs will inspire the development of future PROTACs with more drug-like properties. Additionally, these HaloPROTACs are useful chemical genetic tools, due to their ability to chemically knock down widely used HaloTag7 fusion proteins in a general fashion
References: ACS Chem Biol. 2015 Aug 21;10(8):1831-7.
