Source 1primary paper2019Journal of the American Chemical Society
Toolkit/pc-PROTAC3
pc-PROTAC3
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
pc-PROTAC3 is a photocaged PROTAC constructed against Bruton's tyrosine kinase (BTK) within a light-inducible protein degradation strategy. The available evidence states that this approach was successfully applied to generate pc-PROTAC3 and that photocaged PROTACs can activate degradation activity upon light exposure.
Usefulness & Problems
Why this is useful
This construct is useful as a light-gated targeted protein degradation reagent, enabling temporal control over PROTAC activity through irradiation. The cited work presents photocaged PROTACs as a general strategy for inducing protein degradation with light, which addresses the need to keep degrader activity inactive until triggered.
Source:
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Problem solved
pc-PROTAC3 addresses the problem of uncontrolled constitutive PROTAC activity by using a caged design that is activated by light. In the supplied evidence, the broader platform is positioned as a method to induce protein degradation on demand rather than continuously.
Problem links
Need precise spatiotemporal control with light input
Derivedpc-PROTAC3 is a photocaged PROTAC constructed for BTK in a light-inducible protein degradation strategy. The reported approach applies light to activate degradation activity from an otherwise caged PROTAC design.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
No technique tags yet.
Target processes
No target processes tagged yet.
Input: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: actuatorswitch architecture: cleavage
The construct is implemented as a photocaged PROTAC and therefore requires light as the input modality for activation. The available evidence identifies BTK as the intended target, but it does not specify the caging group, linker architecture, E3 ligase recruiter, irradiation parameters, or delivery conditions for pc-PROTAC3.
The supplied evidence does not provide direct performance data for pc-PROTAC3, such as degradation potency, kinetics, wavelength dependence, selectivity, or cellular context. Conditional live-cell degradation after irradiation is explicitly described for pc-PROTAC1, but independent validation details for pc-PROTAC3 are not included here.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
Approval Evidence
1 source1 linked approval claimfirst-pass slug pc-protac3
this approach was successfully applied to construct pc-PROTAC3 of BTK
Source:
generalizabilitysupports
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
Source:
Comparisons
Source-backed strengths
The main reported strength is conditional activation: the source article states that photo-caged PROTACs can induce protein degradation activity with light. The evidence also indicates that the approach was successfully extended to a BTK-directed construct, pc-PROTAC3, supporting target-specific implementation within the platform.
Compared with alkynyl-functionalized photocleavable linker
pc-PROTAC3 and alkynyl-functionalized photocleavable linker address a similar problem space.
Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light
Compared with Opto-Casp8-V2
pc-PROTAC3 and Opto-Casp8-V2 address a similar problem space.
Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light
pc-PROTAC3 and randomly attached cage compounds on silencing oligonucleotides address a similar problem space.
Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light
Ranked Citations
- 1.