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

Water Solubility 

water: 1.7mg/mL
DMSO: 35mg/mL
ethanol: 35mg/mL

InChI

1S/C20H20N2O4/c1-3-12-8-14(16(24)10-15(12)23)20-19(11(2)21-22-20)13-4-5-17-18(9-13)26-7-6-25-17/h4-5,8-10,23-24H,3,6-7H2,1-2H3,(H,21,22)

InChIKey

OWPMENVYXDJDOW-UHFFFAOYSA-N

SMILES

[nH]1nc(c(c1C)c3cc4c(cc3)OCCO4)c2c(cc(c(c2)CC)O)O

Safety Information

WGK Germany 

WGK 2

Storage Class

11 - Combustible Solids

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