Active Degraders

Degraders (e.g.PROTACs™, SNIPERs etc), are a new approach for the knockdown of target proteins within cells. Comprising binding moieties for an E3 ubiquitin ligase and a target protein joined by a linker, these hybrid molecules induce selective, proteasome-dependent degradation of target proteins and can be used to investigate downstream effects of protein knockdown or to interfere with specific signaling pathways.

Products
Background
Literature

Ligands

Cat No Product Name / Activity
6356 AT 1
(+)-JQ1 based PROTAC with selectivity for BRD4
6416 CM 11
Homo-PROTAC for self-degradation of pVHL30
6327 dBET1
(+)-JQ1 based PROTAC targeting BET bromodomains, active in vivo
6606 dBRD9
Potent and selective BRD9 degrading PROTAC
6607 dTRIM 24
TRIM24 degrading PROTAC
6154 MZ 1
(+)-JQ1 based PROTAC that selectively degrades BRD4 in cells
6532 THAL SNS 032
Potent and selective CDK9 degrading PROTAC
6524 TL 12-186
Multikinase degrading PROTAC

Controls

Cat No Product Name / Activity
6155 cis MZ 1
Negative Control for MZ1
6157 cis VH 298
Negative control for VH 298
6417 CMP 98
Negative Control for CM 11
6525 TL 13-27
Negative control for TL 12-186

Other

Cat No Product Name / Activity
1956 Bestatin
Aminopeptidase inhibitor
6305 Lenalidomide
Cereblon binder; induces ubiquitination and degradation of CK1a by E3 ubiquitin ligase
3984 Nutlin-3
MDM2 antagonist; inhibits MDM2-p53 interaction
6075 Nutlin 3a
MDM2 antagonist; active enantiomer of Nutlin-3
6302 Pomalidomide
Cereblon ubiquitination inhibitor
0652 Thalidomide
Binds cereblon, inhibiting ubiquitin ligase activity
6156 VH 298
High-affinity inhibitor of VHL

Degraders (e.g.PROTACs™, SNIPERs etc), are a new approach for the knockdown of target proteins within cells. Comprising binding moieties for an E3 ubiquitin ligase and a target protein joined by a linker, these hybrid molecules induce selective, proteasome-dependent degradation of target proteins and can be used to investigate downstream effects of protein knockdown or to interfere with specific signaling pathways. The methodology provides an attractive alternative to RNAi methods and have several advantages including:

  • Ease of use: Degraders are cell permeable small molecules that can be applied directly to cells with no need for expression vectors or transfection
  • The duration of effect is adjustable and can be reversed on compound washout
  • Broad applicability to different cell lines, small molecule Degraders do not require cells that are easily transfectable
  • Catalytic mode of action: they dissociate following ubiquitination and rebind to new target proteins, which allows their use at sub-stoichiometric concentrations.

Another interesting feature of small molecule Degraders is their ability to confer additional selectivity, compared to the profile of the target protein ligand used. This is exemplified by AT 1 (Cat. No. 6356), which selectively degrades BRD4, whereas the target protein ligand component of AT 1, (+)- JQ1 (Cat. No. 4499), inhibits the closely related bromodomains of multiple BET family proteins.

Degraders are pharmacologically characterized by their DC50 and DMax values. These values can be used as a guide for the appropriate starting concentrations to use for your experiment. The DC50 is analogous to traditional IC50 values and is the concentration of Degrader at which 50% of the target protein is degraded. The DMax is the maximum level of degradation achievable.

An important factor to consider when using these products is the timescale required for maximum efficacy. This depends on the individual Degrader used; customers are referred to the references provided for each product for guidance. Another consideration is the 'hook effect', which leads to reduced degradation efficiency when high concentrations of compound are applied to cells. This is due to the formation of binary complexes, that compete with formation of the ternary complexes (E3 ligase-Degrader-target protein) required to achieve degradation. In general, very low concentrations of Degrader are required to achieve effective knock down.

Literature for Active Degraders

Tocris offers the following scientific literature for Active Degraders to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


New Product Guide

New Product Guide (Fall/Winter 2018/2019)

Our new product guide highlights over 190 new products added to the Tocris Bioscience range during the second half of 2018.

  • 7-TM Receptors
  • Enzymes
  • Enzyme-Linked Receptors
  • Ion Channels
  • Nuclear Receptors
  • Transporters
  • Chemogenetics
  • Epigenetics
  • Fluorescent Imaging
  • PROTACs
  • Signal Transduction
  • Stem Cells