171009-07-7 Usage
Uses
Used in Pharmaceutical Industry:
CCT 018159 is used as a pharmaceutical agent for targeting the Hsp90 ATPase enzyme. Its inhibition can lead to the destabilization and degradation of various client proteins involved in cancer cell survival and growth, making it a potential therapeutic candidate for the treatment of cancer.
Used in Cancer Research:
In the field of cancer research, CCT 018159 is utilized as a research tool to study the role of Hsp90 ATPase in the development and progression of cancer. By inhibiting this enzyme, researchers can gain insights into the molecular mechanisms underlying cancer and identify potential therapeutic targets.
Used in Drug Development:
CCT 018159 serves as a lead compound in drug development efforts aimed at discovering novel Hsp90 ATPase inhibitors. Its unique chemical structure and inhibitory properties make it a valuable starting point for the design and synthesis of new compounds with improved potency, selectivity, and pharmacological properties.
Used in Drug Screening:
In the process of drug screening, CCT 018159 is employed as a reference compound to evaluate the activity of other potential Hsp90 ATPase inhibitors. This helps in the identification of promising candidates with similar or superior inhibitory effects, which can be further optimized for therapeutic applications.
Overall, CCT 018159 is a versatile compound with significant potential in various applications across the pharmaceutical and biotechnology industries, particularly in the development of novel therapeutics for cancer treatment and the study of molecular mechanisms underlying the disease.
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
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).
Check Digit Verification of cas no
The CAS Registry Mumber 171009-07-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,7,1,0,0 and 9 respectively; the second part has 2 digits, 0 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 171009-07:
(8*1)+(7*7)+(6*1)+(5*0)+(4*0)+(3*9)+(2*0)+(1*7)=97
97 % 10 = 7
So 171009-07-7 is a valid CAS Registry Number.
InChI:InChI=1/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)
171009-07-7Relevant articles and documents
Synthetic and modified isoflavonoids. XV. Intereaction of synthetic analogs of isoflavones with hydrazine hydrate and its derivatives
Khilya, V. P.,Aitmambetov, A.,Ismailov, M.,Grishko, L. G.
, p. 580 - 583 (1994)
The reactions 1,3-benzodioxolane, 1,4-benzodioxane, and 1,5-benzodioxepane analogs of isoflavones with hydrazine derivatives have been studied.It has been found that under the action of hydrazines the new isoflavones recyclize into 3,4-diarylpyrazones.The
The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors
Cheung, Kwai-Ming J.,Matthews, Thomas P.,James, Karen,Rowlands, Martin G.,Boxall, Katherine J.,Sharp, Swee Y.,Maloney, Alison,Roe, S. Mark,Prodromou, Chrisostomos,Pearl, Laurence H.,Aherne, G. Wynne,McDonald, Edward,Workman, Paul
, p. 3338 - 3343 (2007/10/03)
High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 μM) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical p
