1253584-84-7 Usage
Biological Activity
nms-e973 is a potent and selective inhibitor of heat shock protein 90 (hsp90) with dc50 value of < 10nm [1].since hsp90 plays an important role in the conformational maturation, stability and function of some oncogenic proteins, the inhibitors of hsp90 are developed as therapeutic for cancers. nms-e973 is a selective inhibitor of hsp90. it binds to hsp90α within the atp binding site with dc50 value of < 10nm. besides that, nms-e973 shows no effect on a panel of 52 various protein kinases such as abl, ack1, akt1 and alk. the ic50 value of it for hsc70 is > 10μm. nms-e973 exerts antiproliferation effects on a2780 tumor cell line and bt-474 breast cancer cell line with ic50 values of 69nm and 110nm, respectively. when treated with mice bearing a2780 xenografts, the intravenous administration of nms-e973 significantly inhibits tumor growth with tgi value of 53% at dose of 30mg/kg. moreover, nms-e973 also displays antitumor activity in tumors resistant to kinase inhibitors such as vemurafenib [1, 2].
references
[1] brasca m g, mantegani s, amboldi n, et al. discovery of nms-e973 as novel, selective and potent inhibitor of heat shock protein 90 (hsp90). bioorganic & medicinal chemistry, 2013, 21(22): 7047-7063.[2] fogliatto g, gianellini l, brasca m g, et al. nms-e973, a novel synthetic inhibitor of hsp90 with activity against multiple models of drug resistance to targeted agents, including intracranial metastases. clinical cancer research, 2013, 19(13): 3520-3532.
Check Digit Verification of cas no
The CAS Registry Mumber 1253584-84-7 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,5,3,5,8 and 4 respectively; the second part has 2 digits, 8 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 1253584-84:
(9*1)+(8*2)+(7*5)+(6*3)+(5*5)+(4*8)+(3*4)+(2*8)+(1*4)=167
167 % 10 = 7
So 1253584-84-7 is a valid CAS Registry Number.
1253584-84-7Relevant articles and documents
Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90)
Brasca, Maria Gabriella,Mantegani, Sergio,Amboldi, Nadia,Bindi, Simona,Caronni, Dannica,Casale, Elena,Ceccarelli, Walter,Colombo, Nicoletta,De Ponti, Anna,Donati, Daniele,Ermoli, Antonella,Fachin, Gabriele,Felder, Eduard R.,Ferguson, Ronald D.,Fiorelli, Claudio,Guanci, Marco,Isacchi, Antonella,Pesenti, Enrico,Polucci, Paolo,Riceputi, Laura,Sola, Francesco,Visco, Carlo,Zuccotto, Fabio,Fogliatto, Gianpaolo
, p. 7047 - 7063 (2013/11/06)
Novel small molecule inhibitors of heat shock protein 90 (Hsp90) were discovered with the help of a fragment based drug discovery approach (FBDD) and subsequent optimization with a combination of structure guided design, parallel synthesis and application of medicinal chemistry principles. These efforts led to the identification of compound 18 (NMS-E973), which displayed significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile.
