934343-74-5 Usage
Uses
NVP-HSP990 is an orally available HSP90 inhibitor.
Biological Activity
hsp990 (nvp-hsp990) is a potent and selective inhibitor of hsp90 with ic50 values of 0.6, 0.8 and 8.5 nm for hsp90α, hsp90β and grp94, respectively [1].heat shock protein 90 (hsp90) is a chaperone protein that stabilizes proteins against heat stress, assists proteins to fold properly and aids in protein degradation. also, hsp90 stabilizes proteins required for tumor growth.hsp990 (nvp-hsp990) is a potent and selective hsp90 inhibitor. nvp-hsp990 bound to the n-terminal atp-binding domain of hsp90. nvp-hsp990 inhibited trap1 atpase activity by 90% with ic50 value of 320 nm. in gtl-16 cells, nvp-hsp990 destabilized the hsp90-p23 complex in a concentration- and time-dependent way. also, nvp-hsp990 decreased c-met with ec50 value of 37 nm and induced hsp70 with ec50 value of 20 nm. nvp-hsp990 inhibited erk and akt phosphorylation with ec50 values of 11 and 6 nm respectively and thus inhibited erk and akt activation. in five human tumor cell lines, nvp-hsp990 inhibited cell growth with gi50 values of 4-40 nm [1]. in glioma tumor-initiating cells, nvp-hsp990 inhibited cell growth with ic50 value of 10-500 nm in a dose-dependent way and reduced cdk2 and cdk4, thus disrupting cell-cycle control [2].in the gtl-16 gastric cancer mice model, nvp-hsp990 exhibited antitumor efficacy [1].
references
[1]. menezes dl, taverna p, jensen mr, et al. the novel oral hsp90 inhibitor nvp-hsp990 exhibits potent and broad-spectrum antitumor activities in vitro and in vivo. mol cancer ther, 2012, 11(3): 730-739. [2]. fu j, koul d, yao j, et al. novel hsp90 inhibitor nvp-hsp990 targets cell-cycle regulators to ablate olig2-positive glioma tumor-initiating cells. cancer res, 2013, 73(10): 3062-3074.
Check Digit Verification of cas no
The CAS Registry Mumber 934343-74-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,3,4,3,4 and 3 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 934343-74:
(8*9)+(7*3)+(6*4)+(5*3)+(4*4)+(3*3)+(2*7)+(1*4)=175
175 % 10 = 5
So 934343-74-5 is a valid CAS Registry Number.
934343-74-5Relevant articles and documents
Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990
McBride, Christopher M.,Levine, Barry,Xia, Yi,Bellamacina, Cornelia,Machajewski, Timothy,Gao, Zhenhai,Renhowe, Paul,Antonios-Mccrea, William,Barsanti, Paul,Brinner, Kristin,Costales, Abran,Doughan, Brandon,Lin, Xiaodong,Louie, Alicia,McKenna, Maureen,Mendenhall, Kris,Poon, Daniel,Rico, Alice,Wang, Michael,Williams, Teresa E.,Abrams, Tinya,Fong, Susan,Hendrickson, Thomas,Lei, Dachuan,Lin, Julie,Menezes, Daniel,Pryer, Nancy,Taverna, Pietro,Xu, Yongjin,Zhou, Yasheen,Shafer, Cynthia M.
, p. 9124 - 9129 (2015/03/14)
Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.
2-AMINO-7,8-DIHYDRO-6H-PYRIDO[4,3-D] PYRIMIDIN-5-ONES
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Page/Page column 59; 69, (2010/11/26)
Disclosed are 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, their stereoisomers, tautomers, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent. Disclosed also are methods of using the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of cellular proliferative, viral, autoimmune, cardiovascular, and central nevous system diseases.
