Name: LY2886721
Brand: Selleck Chemicals
SKU: S2156
Rating: 5 (19 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.99%

99.99

Dianas relacionadas	Adrenergic Receptor AChR 5-HT Receptor COX Calcium Channel Histamine Receptor Dopamine Receptor GABA Receptor TRP Channel Cholinesterase (ChE)
Otros BACE Inhibidores	Verubecestat (MK-8931) LY2811376 Verubecestat (MK-8931) Trifluoroacetate AZD3839 Lanabecestat (AZD3293) Elenbecestat Loganin LX2343

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	390.41	Fórmula	C₁₈H₁₆F₂N₄O₂S	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	1262036-50-9	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	C1C2CSC(=NC2(CO1)C3=C(C=CC(=C3)NC(=O)C4=NC=C(C=C4)F)F)N

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 35 mg/mL (89.64 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	1.75mg/ml (4.48mM)	Taking the 1 mL working solution as an example, add 50 μL of 35 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	0.25mg/ml (0.64mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Targets/IC₅₀/Ki	BACE2 (Cell-free assay) 10.2 nM BACE1 (Cell-free assay) 20.3 nM
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. This compound can also targetγ-secretase to nhibit the synthesis of β-amyloid. It inhibits recombinant hBACE1 with an IC50 of 20.3 nM. In cellular assays, this chemical inhibits Abeta with an IC50 of 18.7 nM and 10.7 nM, HEK293Swe and PDAPP neuronal culture, respectively. It 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 its activity against hBACE2 demonstrates an IC50 of 10.2 nM. Assessment of the compound's 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 this compound. Brain C99 and sAPPb levels also are reduced in a dose-dependent manner consistent with BACE1 inhibition in vivo. The pharmacodynamic responses to this chemical 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 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. 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. This compound is freely permeable across the blood-brain barrier.
Referencias	[1] http://www.alz.org/ct/documents/adru_studies_2012_04_01.pdf [2] https://pubmed.ncbi.nlm.nih.gov/21368375/ [3] http://www.alzheimersanddementia.com/article/S1552-5260(12)00367-6/abstract [4] https://pubmed.ncbi.nlm.nih.gov/25609634/

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT01807026	Completed	Alzheimer Disease\|Healthy Volunteers	Eli Lilly and Company	March 2013	Phase 1
NCT01534273	Completed	Healthy Volunteers	Eli Lilly and Company	February 2012	Phase 1
NCT01367262	Completed	Healthy Volunteers	Eli Lilly and Company	June 2011	Phase 1
NCT01227252	Completed	Alzheimer''s Disease	Eli Lilly and Company	December 2010	Phase 1
NCT01133405	Completed	Alzheimer''s Disease	Eli Lilly and Company	June 2010	Phase 1

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LY2886721 BACE inhibitor

Estructura química

Peso molecular: 390.41