Ciliobrevin A

Research use only, not for human use.

A small molecule Hedgehog pathway inhibitor (IC50=7 uM) that acts downstream of Su(fu) to modulate Gli processing, activation or trafficking.

A small molecule Hedgehog pathway inhibitor (IC50=7 uM) that acts downstream of Su(fu) to modulate Gli processing, activation or trafficking; does not directly target Smo, blocks the proliferation of cerebellar granule neuron precursors expressing an oncogenic form of Smo; disrupts spindle pole assembly and kinetochore-microtubule attachment, inhibits melanosome aggregation and peroxisome motility in cultured cells; inhibits AAA+ ATPase motor cytoplasmic dynein.

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.

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HPI-4 | HH pathway inhibitor 4

GPCR/G Protein

Hedgehog (Hh)

Hedgehog

Cancer

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302803-72-1

358.1783

C17H9Cl2N3O2

>98% (HPLC)

DMSO: ≥ 34 mg/mL

N#C/C(C(C1=CC=C(Cl)C=C1Cl)=O)=C(N2)/NC3=C(C=CC=C3)C2=O

Benzenepropanenitrile, 2,4-dichloro-α-(3,4-dihydro-4-oxo-2(1H)-quinazolinylidene)-β-oxo-

(-20℃)

With Ice Pack

≥ 2 years