SMASh: A drug-inducible protein turnover control system

SMASh (Small-Molecule-Assisted Shutoff) degron system was developed and optimized to allow targeted and time-controlled degradation of a protein of interest. It was built as a self-cleaving degron that can be stabilized upon drug treatment (Chung HK et al. Nat Chem Biol 2015).

This drug-inducible and reversible protein degradation system is of particular interest to model-targeted protein degradation therapeutic approaches in preclinical stages (learn more: Targeted Protein Degradation: New Promises for "Undruggable" Diseases). It can also be used to create targeted inducible and reversible knock-out and knock-down systems.

SMASh does not need to be coupled to any other reagent to function; a single genetic modification allows for the development of an inducible and reversible targeted protein degradation system.

Access to a new innovative technology for targeted time-controlled protein degradation

The SMASh degron system was developed and first described in 2015 (Chung HK et al. Nat Chem Biol 2015 and US62/186,339). It has been shown to be functional in yeast, virus, and mammalian cells, and has been used in drug discovery (Rago et al. Biochem Biophys Res Commun 2019).

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How it works

Without the drug, the SMASh tag self-cleaved from the protein of interest and is then degraded, with an unchanged level of expression of the protein of interest.

With the drug (in green), the SMASh-tag is stabilized and so, does not self-cleave, allowing for targeted degradation of the protein of interest.

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Key references

Rago F, DiMare MT, Elliott G, Ruddy DA, Sovath S, Kerr G, Bhang HC, Jagani Z. Degron mediated BRM/SMARCA2 depletion uncovers novel combination partners for treatment of BRG1/SMARCA4-mutant cancers. Biochem Biophys Res Commun. 2019 Jan 1;508(1):109–116.

Chung HK, Jacobs CL, Huo Y, Yang J, Krumm SA, Plemper RK, Tsien RY, Lin MZ. Tunable and reversible drug control of protein production via a self-excising degron. Nat Chem Biol. 2015 Sep;11(9):713–20.

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genOway licenses secure your discoveries and research

genOway holds an exclusive license on SMASh for all uses in research tools.

You, the customer, are granted a permanent license under all technologies employed to create the model. This guarantees you its use for any and all relevant R&D purposes.

You also retain ownership of the deliverables and can patent the model developed. genOway has no claim on the results generated using the model we provide to you.