Ciliobrevin A

Ciliobrevin A (HPI-4) is a hedgehog (Hh) signaling pathway inhibitor with median inhibitory concentration (IC50) less than 10 μM.

Product information

CAS Number: 302803-72-1

Molecular Weight: 358.18

Formula: C17H9Cl2N3O2

Synonym:

HPI-4

Chemical Name: 3-(2, 4-dichlorophenyl)-3-oxo-2-[(2Z)-4-oxo-1, 2, 3, 4-tetrahydroquinazolin-2-ylidene]propanenitrile

Smiles: N#C/C(=C1/NC(=O)C2=CC=CC=C2N/1)/C(=O)C1=CC=C(Cl)C=C1Cl

InChiKey: SESYPWCSIZUIAS-VBKFSLOCSA-N

InChi: InChI=1S/C17H9Cl2N3O2/c18-9-5-6-10(13(19)7-9)15(23)12(8-20)16-21-14-4-2-1-3-11(14)17(24)22-16/h1-7,21H,(H,22,24)/b16-12-

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 100 mg/mL (279.19 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

References:

1. Hyman JM, et al. Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14132-7.

Products are for research use only. Not for human use.