471905-41-6 Usage
Description
cis-4-[(4-Chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexanepropanoic acid, also known as MK-0752, is a chemical compound with potent inhibitory properties against the γ-secretase enzyme. It is characterized by its ability to modulate the Notch pathway and reduce the generation of amyloid β protein, making it a promising candidate for therapeutic applications in various medical conditions.
Uses
Used in Pharmaceutical Industry:
MK-0752 is used as a gamma-secretase inhibitor for the treatment of Alzheimer's disease. It works by reducing the cleavage of β-amyloid precursor protein (APP) to Aβ40 in human neuroblastoma SH-SY5Y cells, with an IC50 value of 5 nM. Its oral bioavailability and ability to cross the blood-brain barrier make it a promising candidate for Alzheimer's therapy.
Used in Oncology:
MK-0752 is used as an inhibitor of the Notch pathway in the treatment of breast cancer. By reducing the number of breast cancer stem cells in tumorgrafts, it enhances the efficacy of the chemotherapy drug docetaxel in mice with breast cancer tumors. This application highlights MK-0752's potential in cancer research and treatment.
Used in Clinical Development:
MK-0752 is currently in clinical development as a gamma-secretase inhibitor, indicating its potential for future therapeutic applications in various medical conditions related to the dysregulation of the γ-secretase enzyme and the Notch pathway.
Biological Activity
mk-0752 is a potent gamma secretase inhibitor in clinical development (ic50 ~50 nm). gamma secretase is an important component in the notch cleavage machinery that catalyzes the cleavage of receptor protein substrates within their transmembrane domain. inhibition of notch inhibits bc cell proliferation in vitro. notch signaling requires gamma secretase, which cleaves notch, releasing the notch intracellular domain (nicd) to activate transcription of target genes. notch signaling plays an important role in normal tissue development, cell fate determination, proliferation, and survival. notch signaling is activated following the binding of cognate ligands that include delta1, delta2, and delta3 and jagged1 and jagged2.i. e. krop, m. kosh, i. fearen, j. savoie, a. dallob, c. matthews, j. stone, e. winer, s. j. freedman and p. lorusso. phase i pharmacokinetic (pk), and pharmacodynamic (pd) trial of the novel oral notch inhibitor mk-0752 in patients (pts) with advanced breast cancer (bc) and other solid tumors. j clin oncol (meeting abstracts) june 2006 vol. 24 no. 18_suppl 10574.maryam fouladi, clinton f. stewart, james olson, lars m. wagner, arzu onar-thomas, mehmet kocak, roger j. packer, stewart goldman, sridharan gururangan, amar gajjar, tim demuth, larry e. kun, james m. boyett and richard j. gilbertson. phase i trial of mk-0752 in children with refractory cns malignancies: a pediatric brain tumor consortium study. jco september 10, 2011 vol. 29 no. 26 3529-3534
Check Digit Verification of cas no
The CAS Registry Mumber 471905-41-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,7,1,9,0 and 5 respectively; the second part has 2 digits, 4 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 471905-41:
(8*4)+(7*7)+(6*1)+(5*9)+(4*0)+(3*5)+(2*4)+(1*1)=156
156 % 10 = 6
So 471905-41-6 is a valid CAS Registry Number.
471905-41-6Relevant articles and documents
A practical synthesis of a γ-secretase inhibitor
Scott, Jeremy P.,Lieberman, David R.,Beureux, Olivier M.,Brands, Karel M. J.,Davies, Antony J.,Gibson, Andrew W.,Hammond, Deborah C.,McWilliams, Chris J.,Stewart, Gavin W.,Wilson, Robert D.,Dolling, Ulf-H.
, p. 4149 - 4155 (2008/02/05)
(Chemical Equation Presented) A practical and scaleable synthesis of the γ-secretase inhibitor 1 is reported. The inhibitor consists of a central trisubstituted cyclohexane core with appended propionic acid, 2,5-difluorophenyl, and 4-chlorophenylsulfonyl
CYCLOHEXYL SULPHONES FOR TREATMENT OF CANCER
-
, (2010/11/25)
Sulphones of formula (I) are disclosed for use in treatment of cancer.
Novel cyclohexyl sulphones
-
, (2008/06/13)
Novel sulphones of formula I are disclosed: The compounds modulate the processing of amyloid precursor protein by gamma-secretase, and hence are useful in the treatment or prevention of Alzheimer's disease.
