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VPA (Valproic acid) HDAC inhibitor

Name: VPA (Valproic acid)
Brand: Selleck Chemicals
SKU: S3944
Rating: 5 (45 reviews)

Cat. No.: S3944

Valproic acid (VPA) is a fatty acid with anticonvulsant properties used in the treatment of epilepsy. It is also a histone deacetylase (HDAC) inhibitor and is under investigation for treatment of HIV and various cancers. This compound induces autophagy and mitophagy by upregulation of BNIP3 and mitochondrial biogenesis by upregulating PGC-1α. Additionally, it activates Notch-1 signaling.

VPA (Valproic acid) HDAC inhibitor Chemical Structure

Estructura química

Peso molecular: 144.21

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Control de calidad (Quality Control)

Lote: Pureza: 99.04%

99.04

Dianas relacionadas	JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Sirtuin
Otros HDAC Inhibidores	ITF-2357 (Givinostat) Hydrochloride Monohydrate Fimepinostat (CUDC-907) Trichostatin A (TSA) Entinostat (MS-275) RGFP966 Quisinostat (JNJ-26481585) Dihydrochloride Tubastatin A Hydrochloride Tubastatin A Mocetinostat (MGCD0103) Ricolinostat (ACY-1215)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	PMID
HEK293	Function assay	1 mM		Increase in protein disulfide isomerase level in HEK293 cells at 1 mM by immunoblot	17566732
HEK293	Function assay	1 mM		Increase in GRP78 protein level in HEK293 cells at 1 mM by immunoblot	17566732
A549	Function assay	150 uM	24 hrs	Inhibition of human HDAC in A549 cells assessed as increase in histone-H4 acetylation at 150 uM after 24 hrs by Western blot	18294844
GM15850	Function assay	400 uM	12 hrs	Inhibition of HDAC in human GM15850 cells assessed as increase in total acetylated histone level at 400 uM after 12 hrs by Western blot analysis	16921367
PC12	Function assay	1 uM	24 hrs	Induction of autophagy in rat stable inducible PC12 cells expressing A53T alpha-synuclein assessed as A53T alpha-synuclein clearance at 1 uM after 24 hrs by densitometric analysis	18391949
PC12	Function assay	1 uM	96 hrs	Induction of autophagy in rat stable inducible PC12 cells expressing EGFP-HDQ74 assessed as soluble EGFP-HDQ74 clearance at 1 uM after 96 hrs by densitometric analysis	18391949
SK-N-MC	Function assay	1 mM	48 hrs	Induction of autophagy in human SK-N-MC cells expressing EGFP-HDQ74 assessed as reduction in EGFP-HDQ74 aggregation at 1 uM after 48 hrs by densitometric analysis	18391949
HL60	Function assay	1 mM	24 hrs	Inhibition of HDAC in human HL60 cells assessed as increase in histone H3 acetylation at 1 mM after 24 hrs by Western blotting method	25304896
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	144.21	Fórmula	C₈H₁₆O₂	Almacenamiento (Desde la fecha de recepción)	2 years -20°C liquid
Nº CAS	99-66-1	--		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	2-Propylvaleric Acid, Valproate			Smiles	CCCC(CCC)C(=O)O

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 29 mg/mL (201.09 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : 29 mg/mL

Ethanol : 29 mg/mL

DMSO : 100 mg/mL (693.43 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 100 mg/mL

Water : 2 mg/mL (超声加热五分钟)

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.
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.	5.000mg/ml (34.67mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 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.
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.	5.000mg/ml (34.67mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 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 make it clear; 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.
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.

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	HDAC HDAC1 (Cell-free assay) 0.4 mM
In vitro	Like lithium, valproic acid (VPA) activates Wnt-dependent gene expression, but unlike lithium, it does not inhibit GSK-3β in vivo. This compound can inhibit GSK-3β-mediated phosphorylation of a CREB peptide in vitro. It may activate Wnt-dependent gene expression through inhibition of HDAC, which in turn leads to both increased expression of β-catenin and de-repression of Tcf/Lef (as well as activation of other HDAC-regulated genes). In vitro, VPA can stimulate glutamic acid decarboxylase, which is involved in GABA biosynthesis, and inhibit GABA transaminase, succinic semialdehyde dehydrogenase, and α-ketoglutarate dehydrogenase, enzymes involved in GABA degradation. It relieves HDAC-dependent transcriptional repression and causes hyperacetylation of histones in cultured cells and in vivo. VPA induces differentiation and/or apoptosis of carcinoma cells, PML-RAR-transformed hematopoietic progenitor cells and leukemic blasts from AML patients. In addition to selectively inhibiting the catalytic activity of class I HDACs, it also induces proteasomal degradation of HDAC2.
In vivo	Valproic acid (VPA) increases the level of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), with acute administration causing a 15-45% increase in GABA in the brains of rodents. It also inhibits tumor growth and metastasis in animal experiments, and is a well-tolerated drug even during long-term treatment.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/11473107/ [2] https://pubmed.ncbi.nlm.nih.gov/11742974/ [3] https://pubmed.ncbi.nlm.nih.gov/12840003/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	p-IKKα/β / IKKα/β / NF-κB p65 / IκBα Acetyl-H3 acetyl-H4		30387821
Growth inhibition assay	Cell viability		28101176

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
NCT04671589	Unknown status	Drug Toxicity	Mabaret Al-Asafara Hospitals	June 2021	Phase 4
NCT04384172	Recruiting	Female Sexual Dysfunction\|Spinal Cord Injuries	University of Michigan\|International Society for the Study of Women''s Sexual Health\|The Craig H. Neilsen Foundation	November 11 2020	Not Applicable
NCT03962829	Terminated	Eating Behavior\|Obesity	University of Birmingham\|University Hospital Birmingham	February 1 2019	Not Applicable
NCT03681158	Completed	Epilepsy	Sanofi	October 5 2018	Phase 1

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