Source 1review2019International Journal of Molecular Sciences
Toolkit/small-molecule pro-survival protein inhibitors
small-molecule pro-survival protein inhibitors
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Structural studies involving Bcl-xL were also the basis for the discovery of the first small-molecule pro-survival protein inhibitors, leading ultimately to the development of a new class of drugs now successfully used for cancer treatment in the clinic.
Usefulness & Problems
Why this is useful
These are small molecules that inhibit pro-survival proteins, with their discovery described as arising from Bcl-xL structural studies. The review links them directly to a clinically successful drug class in cancer treatment.; chemical inhibition of pro-survival Bcl-2 family proteins; translating structural knowledge into drug discovery; probing apoptosis-regulatory mechanisms
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These are small molecules that inhibit pro-survival proteins, with their discovery described as arising from Bcl-xL structural studies. The review links them directly to a clinically successful drug class in cancer treatment.
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chemical inhibition of pro-survival Bcl-2 family proteins
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translating structural knowledge into drug discovery
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probing apoptosis-regulatory mechanisms
Problem solved
They solve the problem of pharmacologically targeting pro-survival proteins that regulate apoptosis. The review presents them as a translational outcome of structural biology.; enabled pharmacological inhibition of pro-survival proteins; converted structural insight into a clinically used drug class
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They solve the problem of pharmacologically targeting pro-survival proteins that regulate apoptosis. The review presents them as a translational outcome of structural biology.
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enabled pharmacological inhibition of pro-survival proteins
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converted structural insight into a clinically used drug class
Problem links
converted structural insight into a clinically used drug class
LiteratureThey solve the problem of pharmacologically targeting pro-survival proteins that regulate apoptosis. The review presents them as a translational outcome of structural biology.
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They solve the problem of pharmacologically targeting pro-survival proteins that regulate apoptosis. The review presents them as a translational outcome of structural biology.
enabled pharmacological inhibition of pro-survival proteins
LiteratureThey solve the problem of pharmacologically targeting pro-survival proteins that regulate apoptosis. The review presents them as a translational outcome of structural biology.
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They solve the problem of pharmacologically targeting pro-survival proteins that regulate apoptosis. The review presents them as a translational outcome of structural biology.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
Structural CharacterizationTarget processes
No target processes tagged yet.
Input: Chemical
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: actuator
The abstract supports that their discovery required structural studies involving Bcl-xL. It does not specify the exact screening, chemistry, or assay resources needed.; discovery depends on structural studies involving Bcl-xL; the abstract does not provide medicinal chemistry or screening workflow details
The abstract does not establish which specific inhibitors, selectivity profiles, or disease settings are covered. It also does not describe limitations such as toxicity or resistance.; the abstract does not name specific inhibitor molecules; the abstract does not specify selectivity, safety, or resistance limitations
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Structural studies involving Bcl-xL enabled discovery of the first small-molecule pro-survival protein inhibitors and ultimately contributed to a clinically used cancer drug class.
Structural studies involving Bcl-xL were also the basis for the discovery of the first small-molecule pro-survival protein inhibitors, leading ultimately to the development of a new class of drugs now successfully used for cancer treatment in the clinic.
Structures of Bcl-xL complexes with pro-apoptotic ligands demonstrated the general features of pro-survival:pro-apoptotic complexes.
Subsequent structures of Bcl-xL complexes with pro-apoptotic ligands demonstrated the general features of all pro-survival:pro-apoptotic complexes.
Bcl-xL provided the first high-resolution structure of any Bcl-2 family member and revealed conserved topology among family members.
The first high-resolution structure of any Bcl-2 family member was of Bcl-xL, which revealed the conserved topology amongst all family members.
Approval Evidence
1 source1 linked approval claimfirst-pass slug small-molecule-pro-survival-protein-inhibitors
Structural studies involving Bcl-xL were also the basis for the discovery of the first small-molecule pro-survival protein inhibitors, leading ultimately to the development of a new class of drugs now successfully used for cancer treatment in the clinic.
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discovery enablersupports
Structural studies involving Bcl-xL enabled discovery of the first small-molecule pro-survival protein inhibitors and ultimately contributed to a clinically used cancer drug class.
Structural studies involving Bcl-xL were also the basis for the discovery of the first small-molecule pro-survival protein inhibitors, leading ultimately to the development of a new class of drugs now successfully used for cancer treatment in the clinic.
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Comparisons
Source-stated alternatives
The abstract contrasts these inhibitors implicitly with protein-protein interaction studies, but does not name alternative therapeutic modalities.
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The abstract contrasts these inhibitors implicitly with protein-protein interaction studies, but does not name alternative therapeutic modalities.
Source-backed strengths
originated from structure-informed discovery; led to a new class of drugs used for cancer treatment in the clinic
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originated from structure-informed discovery
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led to a new class of drugs used for cancer treatment in the clinic
Compared with bacterial degrons
small-molecule pro-survival protein inhibitors and bacterial degrons address a similar problem space.
Shared frame: same top-level item type; same primary input modality: chemical
small-molecule pro-survival protein inhibitors and Pyr-NHS-functionalised 3D graphene foam electrode biosensor address a similar problem space.
Shared frame: same top-level item type; same primary input modality: chemical
Compared with rM3Ds
small-molecule pro-survival protein inhibitors and rM3Ds address a similar problem space.
Shared frame: same top-level item type; same primary input modality: chemical
Ranked Citations
- 1.