Tubulin assembly inhibitor

Fig. (4). A combination of 3,4-methylenedioxy-5,4 -dimethoxy-3 -amino-( -stilbene with the des-Doe tetrapeptide unit of the tubulin assembly inhibitor dolastatin 10...

Halichondrin B (7), a highly cytotoxic metabolite isolated from the Japanese sponge H. okadai is a tubulin assembly inhibitor,which binds to the colchicine domain. The macrocyclic portion seems to be essential for the activityEribulin (E7389 146) is a drug candidate designed on the basis of the macrocyclic portion of halichondrin B and is now under phase II/III trials for breast cancer conducted by Eisei Co. Ltd., Tokyo. ... 

Sarcina M, Mullineaux CW Effects of tubulin assembly inhibitors on cell division in prokaryotes in vivo. 

Figure 11. Aromatic thiocyanate tubulin assembly inhibitors. DCBT (20) and WR85915 (21).

Selective glycogen synthase kinase inhibitors (2004BMCL413), cardiovascular agents (1996JMC2922) and inhibitors of tubulin assembly (1996BCF251, 2000TL5853) of the fused benzoheteropine type have been reported. 

More recently a series of derivatives with nitro or serinamide substituents at the 2 5 or 6 position of Combretastatin A-4 were synthesized via a typical Wittig reaction. Some of them are strong inhibitors of tubulin assembly and vascular disrupting agents [21]. 

Schematic representation of the actions of mitotic spindle inhibitors on tubulin assembly. The drug binds to tubulin in S, and disrupts the assembly of microtubules.

Discodermolide (DDM, Fig. 16) is a marine natural product that promotes MT assembly more potently than PTX and is active against some PTX-resistant cell lines [118-120], The photoaffmity analogue C19-BPC-DDM labels (3-tubulin in close proximity to the taxol binding site [121] and DDM itself is a competitive inhibitor of PTX binding to MT [120], suggesting that DDM also binds to the PTX binding site on P-tubulin. 

The X-ray crystallographic analysis of T2R crystals soaked with vinblastine has revealed its binding site between the two tubulins of this short protofilament-like curved assembly (Fig. 6) [55]. It is equally contributed by the a-subunit of one tubulin and the [i-subuni I of the other. Vinblastine therefore belongs to the growing class of small molecules ligands known as interfacial inhibitors [58] these... 

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