WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 525670
Description: MK0752 is a synthetic small molecule with potential antineoplastic activity. MK0752 inhibits the Notch signaling pathway, which may result in induction of growth arrest and apoptosis in tumor cells in which the Notch signaling pathway is overactivated. The Notch signaling pathway plays an important role in cell-fate determination, cell survival, and cell proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
MedKoo Cat#: 525670
Chemical Formula: C21H21ClF2O4S
Exact Mass: 442.08171
Molecular Weight: 442.9
Elemental Analysis: C, 56.95; H, 4.78; Cl, 8.00; F, 8.58; O, 14.45; S, 7.24
Synonym: Code name: MK0752. Chemical name: cis34(3chlorophenyl)sulfonyl4(25difluorophenyl)cyclohexyl propanoicacid.
IUPAC/Chemical Name: 3-((1r,4s)-4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid.
InChi Key: XCGJIFAKUZNNOR-HNSKJHPRSA-N
InChi Code: InChI=1S/C21H21ClF2O4S/c22-15-2-5-17(6-3-15)29(27,28)21(18-13-16(23)4-7-19(18)24)11-9-14(10-12-21)1-8-20(25)26/h2-7,13-14H,1,8-12H2,(H,25,26)/t14-,21-
SMILES Code: O=C(O)CC[C@H]1CC[C@](C2=CC(F)=CC=C2F)(S(=O)(C3=CC=C(Cl)C=C3)=O)CC1
MK-0752 is a potent gamma secretase inhibitor in clinical development (IC50 50 nM). Phase I clinical trials results reported in 2006 showed that MK-0752 was well-tolerated in a limited number of patients below 300 mg/m2, and further enrollment was underway to establish the MTD. Plasma concentrations of MK-0752 at all doses were sufficient to inhibit gamma secretase. (source: D. J. Deangelo, R. M. Stone, L. B. Silverman, W. Stock, E. C. Attar, I. Fearen, A. Dallob, C. Matthews, J. Stone, S. J. Freedman and J. Aster (Dana-Farber Cancer Institute, Boston, MA; University of Chicago, Chicago, IL; Massachusetts General Hospital, Boston, MA; Merck Research Laboratories, West Point, PA; Brigham and WomenÂ’s Hospital, Boston, MA, A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias, Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 24, No 18S (June 20 Supplement), 2006: 6585, webpage: http://meeting.ascopubs.org/cgi/content/abstract/24/18_suppl/6585).
1: Bai F, Tagen M, Colotta C, Miller L, Fouladi M, Stewart CF. Determination of the gamma-secretase inhibitor MK-0752 in human plasma by online extraction and electrospray tandem mass spectrometry (HTLC-ESI-MS/MS). J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2348-52. Epub 2010 Jul 30. PubMed PMID: 20702149; PubMed Central PMCID: PMC2926936.
2: Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ. Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. J Neurosci. 2010 May 12;30(19):6743-50. PubMed PMID: 20463236; PubMed Central PMCID: PMC2913973.
3: Matthews CZ, Woolf EJ. Determination of a novel gamma-secretase inhibitor in human plasma and cerebrospinal fluid using automated 96 well solid phase extraction and liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Feb 15;863(1):36-45. Epub 2008 Jan 6. PubMed PMID: 18249589.
4: Olson RE, Albright CF. Recent progress in the medicinal chemistry of gamma-secretase inhibitors. Curr Top Med Chem. 2008;8(1):17-33. Review. PubMed PMID: 18220929.