Ciliobrevin A

• CAT Number: I003058
• CAS Number: 302803-72-1
• Molecular Formula: C17H9Cl2N3O2
• Molecular Weight: 358.2
• Purity: ≥95%
• Target: Hedgehog
• Solubility: DMSO: ≥ 34 mg/mL
• Storage: Store at +4C
• InChIKey: SESYPWCSIZUIAS-VBKFSLOCSA-N

Ciliobrevin A is a hedgehog (Hh) signaling pathway inhibitor with median inhibitory concentration (IC50) less than 10 μM.IC50: ＜10 μM (Hedgehog)[1]InVitro: Ciliobrevin A (HPI-4) also prevents an increase in the FLAG-Gli2 full-length/repressor ratio upon Shh stimulation, but HPI-2 and HPI-3 have no significant effect. Ciliobrevin A decreases FLAG-Gli1 stability in these cells, revealing another mechanism by which this small molecule can inhibit Hh target gene expression, while neither HPI-2 or HPI-3 has any significant effect on FLAG-Gli1 levels. Ciliobrevin A increases ciliary levels of FLAG-Gli2 in a manner disproportionate to their effects on total FLAG-Gli2 levels. In addition, Shh-EGFPFLAG-Gli2 cells cultured with Ciliobrevin A have truncated primary cilia, and this cellular organelle is absent in a significant fraction of Ciliobrevin A-treated cells. Ciliobrevin A also perturbs primary cilia formation in the Shh-LIGHT2FLAG-Gli1 cells and promotes accumulation of FLAG-Gli1 at the distal tip of this organelle. Ciliobrevin A significantly inhibits the proliferation of these neuronal progenitors, as measured by histone H3 phosphorylation (pH3) levels, and reduces cellular levels of cyclin D1 protein and Gli1, Gli2, and N-Myc transcripts in the CGNPs. Ciliobrevin A can block the proliferation of SmoM2-expressing CGNPs and should be equally potent against CGNPs lacking Su(fu) function, whereas the Smo inhibitor Cyclopamine is ineffective against either oncogenic lesion[1].

Reference

1:Mol Biochem Parasitol. 2017 Apr 5;214:75-81. doi: 10.1016/j.molbiopara.2017.04.003. [Epub ahead of print] Characterization of ciliobrevin A mediated dynein ATPase inhibition on flagellar motility of Leishmania donovani.Reddy GS,Mukhopadhyay AG,Dey CS, PMID: 28389272 DOI: 10.1016/j.molbiopara.2017.04.003 Abstract: Axonemal dyneins are members of AAA+ proteins involved in force generation and are responsible for flagellar motility in eukaryotes. In this study, we characterized the effects of ciliobrevin A (CbA), a dynein ATPase inhibitor, on flagella driven motility of the protozoan parasite Leishmania donovani. Using fast-capture video microscopy, we observed that CbA decreased flagellar beat frequency of swimming parasites in a concentration-dependent manner. Beat frequency of live and reactivated L. donovani decreased by approximately 89% and 41% respectively in the presence of 250μM CbA. This inhibition was lost when CbA was removed, suggesting its effects were reversible. CbA also altered wavelength and amplitude of the flagellum of live parasites. Waveform analysis of live and reactivated L. donovani revealed that CbA significantly affected flagellar waveform by inducing non-uniform bends with the flagellum beating away from the cell axis. These results suggest that CbA sensitive dynein ATPases possibly are responsible for power generation and waveform maintenance of the flagellum of L. donovani. This ability to inhibit axonemal dyneins also emphasizes the use of dynein inhibitors as valuable tools in studying functional roles of axonemal dyneins of flagellated eukaryotes.Copyright © 2017. Published by Elsevier B.V.