Eleutherobin

Inhibitor of TUBB

Structure

Information

Protein target names: TUBB

Mechanism of action: Inhibitor

Recommended in-cell concentration:
250-500 nM

In Vitro Validations

Uniprot ID: P07437
Target Class: Enzyme
Target SubClass: GTPase
Potency: EC50
Potency Value: 6500 nM
Potency Assay: In vitro calf brain tubulin polymerization assays,
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Tubulin beta chain, TUBB5, TUBB, TBB5_HUMAN, Tubul ...

PMID Reference: 9515790

In Cell Validations

In Vivo Data

No in Vivo Validations

I have extra information to add

SERP ratings and comments


SERP Ratings

In Cell Rating

(last updated: 15 May 2020 )

SERP Ratings

In Cell Rating

Comments:

Eleutherobin is the prototypical member of the eleutherobin class of tubulin inhibitors, consisting of 7 unique agents each isolated from several species of marine sponges. Its structure is well defined by NMR and the active enantiomer of the compound (based heavily on the orientation of the carbohydrate R-group motif) has been described. A synthetic pathway for its synthesis is published and freely available. Utilising direct binding experiments for tubulin stabilisation in a variety of approaches including reactions in free solution and in cellular models, eleutherobin demonstrates strong binding to tubulin which is consistently 5-10 fold less potent than the commonly utilised taxol, paclitaxel. Direct binding of eleutherobin to tubulin has been confirmed and it directly competes with paclitaxel for binding, suggesting that these drugs share a common binding site and mechanism. The inhibitory dose 50 (IC50) anti-prolferaitve range for this drug in multiple cancer cell lines is approximately10-140 nM. Use of a low concentration (50nM) of eleutherobin in cellular models induces microtubule stabilisation, cell cycle arrest at the G2/M phase and phenotypic nuclear morphology changes associated with mitotic catastrophe and mitotic slippage. Eleutherobin is also a substrate for the drug efflux pump, P-glycoprotein, which must be taken into account when selecting the cellular model to test the drug in. Additionally, eleutherobin can still bind and stabilise tubulin mutants which predispose to paclitaxel resistance which highlights the usefulness of eleutherobin in acting as an alternative tubulin probe in the context of this genetic background. Elutherobin is, therefore, a potent probe of tubulin biology in cellular models, including those bearing paclitaxel-nullifying tubulin mutations. Although SAR has been performed, the precise mode of binding to tubulin is not defined. Moreover, the potential for incidental ‘off targets’ with relevance to cell biology is incompletely mapped. Commercial supply of elutherobin is limited, with no vendors currently listed to purchase the drug, limiting its wider spread use as a commonly utilised probe.   

(last updated: 7 Jun 2020 )

SERP Ratings

In Cell Rating

Comments:

Even if the direct activity of eleutherobin on tubulin has been demonstrated in vitro, some structural components are potentially reactive (such as the Michael acceptor) and reversible and/or irreversible interactions with other targets may contribute to its activity in cells.

(last updated: 4 Nov 2020 )