LY2886721 - Moligand™, 10mM in DMSO , Inhibitor of beta-secretase 1, CAS No.1262036-50-9, Inhibitor of beta-secretase 1

CAS: 1262036-50-9 Cat. No.: L409170 Molecular Weight: 390.41

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

N-(3-((4aS,7aS)-2-amino-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

LY2886721 LY2886721 is a BACE inhibitor used for the treatment of Alzheimer's Disease. Phase 1/2.
In vitro

LY2886721 is an oral, small molecule of β-site amyloid protein cleaving enzyme (BACE) inhibitor with the potential to inhibit the synthesis of β-amyloid and thereby to slow the clinical progression of AD. LY2886721 can also targetγ-secretase to nhibit the synthesis of β-amyloid. LY2886721 inhibits recombinant hBACE1 with an IC50 of 20.3 nM. In cellular assays, LY2886721 inhibits Abeta with an IC50 of 18.7 nM and 10.7 nM, HEK293Swe and PDAPP neuronal culture, respectively. LY2886721 has high selectivity against key off-target proteases, which efficiently translates in vitro activity into robust in vivo amyloid β lowering in nonclinical animal models. Assessment of LY2886721 activity against hBACE2 demonstrates an IC50 of 10.2 nM. Assessment of LY2886721 activity against cathepsin D, pepsin, renin, or other important aspartyl proteases shows essentially no inhibition (IC50 >100,000 nM), suggesting that activity against these common aspartyl proteases is unlikely to be significant.

In vivo

Oral administration of LY2886721 to PDAPP mice produces dose-dependent reductions in brain Abeta, C99 and sAPPbeta. Brain Abeta levels are decreased ∼20%-65% relative to vehicle-treated groups three hours after a 3-30 mg/kg dose of LY2886721. Brain C99 and sAPPb levels also are reduced in a dose-dependent manner consistent with BACE1 inhibition in vivo. The pharmacodynamic responses to LY2886721 persists out to 9 hours post dose in brains of PDAPP mice. Pharmacodynamic studies in beagle dog reveal robust and sustained reductions in plasma Abeta following 1 mg/kg LY2886721 dosing. Central effects of BACE1 inhibition in dog are manifested by a 50% reduction in CSF Abeta at 9 hours after a 0.5 mg/kg dose of LY2886721. The geometric mean terminal elimination t1/2 is determined to be 17.2 h (range 8.19-36.3 h). The geometric mean apparent oral clearance is 34.8 L/h (38% CV) and the apparent volume of distribution during the terminal phase was 863 L (56% CV) across dose levels. LY2886721 is freely permeable across the blood-brain barrier.
Cell Data

cell lines：

Concentrations：--

Incubation Time：Overnight exposure

Powder Purity:≥99%

Specifications

Synonyms

N-(3-((4aS, 7aS)-2-amino-4a, 5, 7, 7a-tetrahydro-4H-furo[3, 4-d][1, 3]thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

LY2886721 is a BACE inhibitor used for the treatment of Alzheimer\'s Disease. Phase 1/2.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of beta-secretase 1

Names and Identifiers

• Isomeric SMILES: C1[C@H]2CSC(=N[C@]2(CO1)C3=C(C=CC(=C3)NC(=O)C4=NC=C(C=C4)F)F)N
• Molecular Weight: 390.41
• Reaxy-Rn: 25251199
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=25251199&ln=

Associated Targets(Human)

BACE1 Tchem Beta-secretase 1 (5 Activities)

Discover Target: BACE1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

BACE2 Tchem Beta-secretase 2 (1 Activities)

Discover Target: BACE2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)