1693731-40-6 Usage
Description
CCT251236 (1693731-40-6) is an inhibitor of the Heat Shock Transcription Factor 1 (HSF1) stress pathway (IC50 = 19 nM Inhibition HSF-1 mediated HSP72 induction, IC50 = 40 nM HSPA1A induction).1 It displayed efficacy in a human ovarian carcinoma xenograft mouse model (SK-OV 3 cells) and inhibited migration of WM266.4 melanoma cells @ 100 nM. CCT251236 showed high affinity for the protein pirin (Ki = 28 nM), but this target was not shown conclusively to be the cause of the anticancer activity. It also showed efficacy in vitro against primary patient-derived myeloma cells and H929 human myeloma xenograft models.2
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.
