1693731-40-6 Usage
Description
N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-2-(2-(pyrrolidin-1-yl)ethoxy)quinoline-6-carboxamide, also known as CCT251236, is a potent inhibitor of the Heat Shock Transcription Factor 1 (HSF1) stress pathway with an IC50 of 19 nM for inhibiting HSF-1 mediated HSP72 induction and 40 nM for HSPA1A induction. It has demonstrated efficacy in various cancer models, including human ovarian carcinoma and melanoma cells, as well as primary patient-derived myeloma cells and H929 human myeloma xenograft models. CCT251236 also exhibits high affinity for the protein pirin (Ki = 28 nM), although its role in the compound's anticancer activity has not been conclusively established.
Uses
Used in Oncology:
N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-2-(2-(pyrrolidin-1-yl)ethoxy)quinoline-6-carboxamide is used as an anticancer agent for various cancer types, including ovarian carcinoma, melanoma, and myeloma. It inhibits the HSF1 stress pathway, which plays a crucial role in the development and progression of cancer, and has shown efficacy in both in vitro and in vivo cancer models.
Used in Drug Development:
N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-2-(2-(pyrrolidin-1-yl)ethoxy)quinoline-6-carboxamide is used in the development of novel therapeutic agents targeting the HSF1 stress pathway. Its high affinity for the protein pirin and its potential role in the compound's anticancer activity make it a promising candidate for further research and development in the field of oncology.
Used in Cancer Research:
N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-2-(2-(pyrrolidin-1-yl)ethoxy)quinoline-6-carboxamide is used as a research tool to study the role of the HSF1 stress pathway in cancer development and progression. Its ability to inhibit HSF1-mediated HSP72 induction and HSPA1A induction makes it a valuable compound for investigating the mechanisms underlying the HSF1 pathway and its potential as a therapeutic target in cancer treatment.
References
Cheeseman et al. (2017), Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen; J. Med. Chem., 60 180
Fok et al. (2018), HSF-1: Essential for Myeloma Cell Survival and A Promising Therapeutic Target; Cancer Res., 124 2395
Check Digit Verification of cas no
The CAS Registry Mumber 1693731-40-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,6,9,3,7,3 and 1 respectively; the second part has 2 digits, 4 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1693731-40:
(9*1)+(8*6)+(7*9)+(6*3)+(5*7)+(4*3)+(3*1)+(2*4)+(1*0)=196
196 % 10 = 6
So 1693731-40-6 is a valid CAS Registry Number.
1693731-40-6Relevant articles and documents
Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen
Cheeseman, Matthew D.,Chessum, Nicola E. A.,Rye, Carl S.,Pasqua, A. Elisa,Tucker, Michael J.,Wilding, Birgit,Evans, Lindsay E.,Lepri, Susan,Richards, Meirion,Sharp, Swee Y.,Ali, Salyha,Rowlands, Martin,O’Fee, Lisa,Miah, Asadh,Hayes, Angela,Henley, Alan T.,Powers, Marissa,Te Poele, Robert,De Billy, Emmanuel,Pellegrino, Loredana,Raynaud, Florence,Burke, Rosemary,Van Montfort, Rob L. M.,Eccles, Suzanne A.,Workman, Paul,Jones, Keith
, p. 180 - 201 (2017/04/26)
Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model. By developing cell-based SAR and using chemical proteomics, we identified pirin as a high affinity molecular target, which was confirmed by SPR and crystallography.
