CCT 018159 Chemical Properties

Boiling point:

547.3±50.0 °C(Predicted)

Density 

1.322±0.06 g/cm3(Predicted)

storage temp. 

Store at +4°C

solubility 

≤30mg/ml in ethanol;30mg/ml in DMSO;30mg/ml in dimethyl formamide

pka

8.84±0.48(Predicted)

form 

White solid

color 

White to off-white

CCT 018159 Usage And Synthesis

Uses

CCT 018159 is a cell-permeable compound that inhibits Hsp90 ATPase.

Definition

ChEBI: A member of the class of pyrazoles that is 1H-pyrazole carrying 1,4-benzodioxane-6-yl and 5-ethyl-2,4-dihydroxyphenyl substituents at positions 4 and 5 respectively.

Biological Activity

Novel inhibitor of heat shock protein 90 (Hsp90) ATPase activity (IC 50 = 5.7 μ M) that displays selectivity over human Hsp72 and topoisomerase II. Inhibits proliferation of HCT116 human colon tumor cells and produces upregulation of Hsp70 and downregulation of c-Raf and cdk4. More soluble than 17-AAG (17-Demethoxy-17-(2-propenylamino)geldanamycin ) and is independent of NQO1/DT-diaphorase and P-glycoprotein expression.

in vitro

cct018159 was identified by high-throughput screening inhibiting human hsp90beta with comparable potency to 17-aag and with similar atp-competitive kinetics. x-ray crystallographic structures of the yeast hsp90 complexed with cct018159 showed binding properties similar to radicicol. the mean cellular gi50 of cct018159 across a panel of human cancer cell lines, including melanoma, was 5.3 μm. unlike 17-aag, the in-vitro antitumor activity of cct018159 was independent of nqo1/dt-diaphorase and p-glycoprotein expression. the signature of hsp90 inhibition, comprising increased expression of hsp72 protein and depletion of erbb2, cdk4, c-raf, and mutant b-raf, was indicated in human cancer cell lines treated with cct018159 [1].

in vivo

in human tumor xenografts including skmel 28 melanoma cells, cct018159 was found to induce the expression of hsp72 as well as erbb2, cdk4 and dc-raf [1].

IC 50

3.2 and 6.6 μm for human hsp90β and yeast hsp90, respectively

storage

Store at +4°C

References

[1] s. y. sharp, k. boxall, m. rowlands, et al. in vitro biological characterization of a novel, synthetic diaryl pyrazole resorcinol class of heat shock protein 90 inhibitors. cancer research 67(5), 2206-2216 (2007).

CCT 018159(171009-07-7)Related Product Information

• 2-(1H-PYRAZOL-3-YL)PHENOL
• 3-(2-HYDROXY-5-METHYLPHENYL)PYRAZOLE
• CCT 018159
• 3-(5-ETHYL-2-HYDROXYPHENYL)PYRAZOLE
• SALOR-INT L249092-1EA