Bistramide A

Severs actin filaments, Covalent sequestration of G-actin of ACTG2

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(1 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

ACTG2

Severs actin filaments, Covalent sequestration of G-actin

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In Vitro Validations

Uniprot ID: P63267

Target Class: Structural protein

Target SubClass: Cytoskeleton

Potency: KD

Potency Value: 7 nM

Potency Assay: Isothermal calorimetry (ITC) assays with G-actin and ATP. In G-actin polymerization experiments, Bistramide A decreased polymerization at concentrations 50-400 nM. In F-actin depolymerization assays, Bistramide A increased depolymerization at concentrations 120-450 nM. These results were confirmed in later experiments using TIRF microscopy (see PNAS paper).

PDB ID for probe-target interaction (3D structure): 2FXU

Target aliases:

Actin, gamma-enteric smooth muscle, ACTSG, ACTL3, ...

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Portal staff comment: Bistramide A is not a PKC δ activator.

(last updated: 17 Jul 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Bistramide A is a novel actin-binding compound that disrupts actin filament formation. The compound has a fairly narrow concentration range and can be used as an orthogonal probe to study actin dynamics.

(last updated: 24 Jul 2017 )

SERP Ratings

In Cell Rating

SERP Comments:

Bistramide A, at submicromolar concentrations, is shown to bind G-actin and sequester the actin molecule from polymerization into F-actin in cells, but at concentrations higher that 10 uM, the compound starts to inhibit PDBu binding to PKCdelta. So researchers should carefully set an experimental concentration range and should carefully interpret the consequences after treatment of cells with the compound, especially in growth inhibition or toxicity assays, which might yield phenotypes for multiple reasons.

(last updated: 16 Nov 2020 )

SERP Comments:

Bistramide A displays good affinity for actin with Kd=7nM. Its activity in cells is reported in the range of 20mM to 750nM (PMID 3238698 and 7807120) depending on the readout and cancer cell line tested. It is also active in normal human endothelial cells (PMID 3238698). Accordingly, a top probe concentration of 300-500nM might be used in parallel with the recommended concentration of 50-100 nM to cover all bases. This probe was tested in vivo but was reported to be too generally toxic to be able to study its anti-tumor activity (PMID 7807120); its testing in vivo is therefore not recommended.

(last updated: 16 Nov 2020 )