ELND006 - CAS 1333990-84-3
Catalog number: 1333990-84-3
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
C20H14F5N3O2S
Molecular Weight:
455.07
COA:
Inquire
Targets:
γ-secretase
Description:
ELND006 is one of the newest molecules to be reported on regarding the testing of the β-amyloid hypothesis. At the 2010 Alzheimer’s Association International Conference on Alzheimer’s Disease in which ELND006 was reported to have an in vitro IC50 = 0.34 nM against APP and IC50 = 5.3 nM versus Notch signaling.
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Brife Description:
A novel oral γ-secretase inhibitor
Appearance:
White solid powder
Synonyms:
(4R)-4-cyclopropyl-7,8-difluoro-5-[4-(trifluoromethyl)phenyl]sulfonyl-1,4-dihydropyrazolo[4,3-c]quinoline; UNII-7F5QGV49GL; ELND006; ELND-006; 959997-22-9; (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline; (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline; 7F5QGV49GL; SCHEMBL486044; GTPL7337; CHEMBL2396778
Solubility:
Soluble in DMSO, not in water
Storage:
Store in a cool and dry place and at 0 - 4℃ for short term (days to weeks) or -48℃ for long term (months to years).
MSDS:
Inquire
InChIKey:
XODSHWXKSMPDRP-LJQANCHMSA-N
InChI:
1S/C20H14F5N3O2S/c21-15-7-13-17(8-16(15)22)28(19(10-1-2-10)14-9-26-27-18(13)14)31(29,30)12-5-3-11(4-6-12)20(23,24)25/h3-10,19H,1-2H2,(H,26,27)/t19-/m1/s1
Canonical SMILES:
C1CC1C2C3=C(C4=CC(=C(C=C4N2S(=O)(=O)C5=CC=C(C=C5)C(F)(F)F)F)F)NN=C3
Current Developer:
Elan Pharmaceuticals
1.Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
Probst G1, Aubele DL, Bowers S, Dressen D, Garofalo AW, Hom RK, Konradi AW, Marugg JL, Mattson MN, Neitzel ML, Semko CM, Sham HL, Smith J, Sun M, Truong AP, Ye XM, Xu YZ, Dappen MS, Jagodzinski JJ, Keim PS, Peterson B, Latimer LH, Quincy D, Wu J, Goldbach J Med Chem. 2013 Jul 11;56(13):5261-74. doi: 10.1021/jm301741t. Epub 2013 Jun 20.
Herein, we describe our strategy to design metabolically stable γ-secretase inhibitors which are selective for inhibition of Aβ generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of Aβ generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered Aβ in the CSF of healthy human volunteers.
2.ACS chemical neuroscience molecule spotlight on ELND006: another γ-secretase inhibitor fails in the clinic.
Hopkins CR1. ACS Chem Neurosci. 2011 Jun 15;2(6):279-80. doi: 10.1021/cn2000469.
ELND006 is a novel γ-secretase inhibitor by Elan Corporation that was in the clinic as a potential treatment for Alzheimer's disease (AD). The clinical trial for ELND006 was halted in October 2010 due to liver side effects that are thought to be unrelated to the mechanism of action. However, this represents another small molecule γ-secretase inhibitor that has failed in clinical trials (semagacestat) (http://newsroom.lilly.com/releasedetail.cfm?releaseid=499794) which raises serious questions regarding this mechanism for the treatment of AD.
3.A formulation strategy for gamma secretase inhibitor ELND006, a BCS class II compound: development of a nanosuspension formulation with improved oral bioavailability and reduced food effects in dogs.
Quinn K1, Gullapalli RP, Merisko-Liversidge E, Goldbach E, Wong A, Liversidge GG, Hoffman W, Sauer JM, Bullock J, Tonn G. J Pharm Sci. 2012 Apr;101(4):1462-74. doi: 10.1002/jps.23034. Epub 2011 Dec 28.
ELND006 is a novel gamma secretase inhibitor previously under investigation for the oral treatment of Alzheimer's disease. ELND006 shows poor solubility and has moderate to high permeability, suggesting it is a Biopharmaceutics Classification System Class II compound. The poor absolute oral bioavailability of the compound in fasted dogs (F ∼11%) is attributed to poor aqueous solubility. In addition, inhibiting amyloid precursor protein but not Notch cleavage is an important goal for gamma secretase inhibitors; therefore, significant variation in bioavailability resulting from food consumption is a potential liability for this class of compounds. The objective of the present study was to determine if an ELND006 nanocrystalline formulation would offer improved and predictable pharmacokinetics. ELND006 was formulated as a nanosuspension with a mean particle size of less than 200 nm, which was stable in particle size and crystallinity for over 1 year.
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CAS 1333990-84-3 ELND006

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