Centrosome is an important organelle. It acts as the main microtubule organizing center (MTOC), regulates cell-cycle progression in mammalian cells. In normal cells, centrosome duplication occurs in the early phase of cell cycle. It ensures each daughter cell to have one centrosome after cell division. CPAP (centrosomal P4.1-associated protein) interacts with tubulin. The latter is a negative regulator of CPAP-dependent peri-centriolar material recruitment and microtubule nucleation. Centrosome amplification is a hallmark in human cancers cells. They may use extra centrosomes for cellular invasion. Thus, it is possible to inhibit CPAP-tubulin interaction to prevent cancer cells with amplified extra centrosomes.

Recently, Aruljothi Mariappan, et al., carried out a study. They wanted to find out a potent CPAP-tubulin interaction inhibitor, and then a small molecule named CCB02 is standing out.

To our satisfaction, CCB02 is a selective tubulin binder, competing for the CPAP binding site of β-tubulin. The IC50 value is 689 nM. However, the conventional tubulin binders don’t occupy this site. CCB02 does not inhibit cycle- and centrosome-related kinases, or the phosphorylation status of Aurora A, Plk1, Plk2, CDK2, and CHK1.

What’s more, in cellular assays, CCB02 prevents the proliferation of cancer cells with extra centrosomes (IC50, 0.86-2.9 μM). Besides, the potent inhibitor activates spindle assembly checkpoint. It also causes PCM proteins recruitment, and increases microtubule nucleation activities of centrosomes.

Further, in animal assays, CCB02 (30 mg/kg, p.o., daily) shows potent anti-tumor activity in nude mice bearing human lung (H1975T790M) tumor xenografts.

In summary, CCB02 needs further research for centrosome functions in cells. It has potential in the therapy of cancer cells with extra centrosomes.