Tubastatin A Hydrochloride

N.º de catálogoS2627 Lote:S262706

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Datos técnicos

Fórmula

C20H21N3O2.HCl
Peso molecular 371.86 Número CAS 1310693-92-5
Solubilidad (25°C)* In vitro DMSO 74 mg/mL (198.99 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Agregue los solventes al producto individualmente y en orden.)
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.
* <1 mg/ml significa ligeramente soluble o insoluble.
* Tenga en cuenta que Selleck prueba la solubilidad de todos los compuestos internamente, y la solubilidad real puede diferir ligeramente de los valores publicados. Esto es normal y se debe a ligeras variaciones entre lotes.
* Envío a temperatura ambiente (Las pruebas de estabilidad demuestran que este producto se puede enviar sin medidas de refrigeración.)

Preparación de soluciones madre

Actividad biológica

Descripción Tubastatin A HCl es un potente y selectivo inhibidor de HDAC6 con una IC50 de 15 nM en un ensayo sin células. Es selectivo (1000 veces más) contra todas las demás isozimas excepto HDAC8 (57 veces más).
Objetivos
HDAC6
(Cell-free assay)		 HDAC8
(Cell-free assay)
15 nM 854 nM
In vitro Tubastatin A is substantially selective for all 11 HDAC isoforms and maintains over 1000-fold selectivity against all isoforms excluding HDAC8, where it has approximately 57-fold selectivity. In homocysteic acid (HCA) induced neurodegeneration assays, Tubastatin A displays dose-dependent protection against HCA-induced neuronal cell death starting at 5 μM with near complete protection at 10 μM. At 100 ng/mL Tubastatin A increases Foxp3+ T-regulatory cells (Tregs) suppression of T cell proliferation in vitro. Tubastatin A treatment in C2C12 cells would lead to myotube formation impairment when alpha-tubulin is hyperacetylated early in the myogenic process; however, myotube elongation occurs when alpha-tubulin is hyeperacetylated in myotubes. A recent study indicates that Tubastatin A treatment increases cell elasticity as revealed by atomic force microscopy (AFM) tests without exerting drastic changes to the actin microfilament or microtubule networks in mouse ovarian cancer cell lines, MOSE-E and MOSE-L.
In vivo Daily treatment of Tubastatin A at 0.5mg/kg inhibits HDAC6 to promote Tregs suppressive activity in mouse models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully major histocompatibility complex (MHC)-incompatible cardiac allograft rejection.

Protocolo (de referencia)

Ensayo de quinasa:[1]
  • Ensayos de inhibición enzimática

    Los ensayos de inhibición enzimática son realizados por Reaction Biology Corporation, Malvern, PA, utilizando la plataforma Reaction Biology HDAC Spectrum. (www.reactionbiology.com) Los ensayos de HDAC1, 2, 4, 5, 6, 7, 8, 9, 10 y 11 utilizan proteína humana recombinante aislada; el complejo HDAC3/NcoR2 se utiliza para el ensayo de HDAC3. El sustrato para los ensayos de HDAC1, 2, 3, 6, 10 y 11 es un péptido fluorogénico de los residuos 379-382 de p53 (RHKKAc); el sustrato para HDAC8 es un dipéptido diacilo fluorogénico basado en los residuos 379-382 de p53 (RHKAcKAc). Se utiliza el sustrato Acetil-Lis (trifluoroacetil)-AMC para los ensayos de HDAC4, 5, 7 y 9. Tubastatin A se disuelve en DMSO y se prueba en modo IC50 de 10 dosis con una dilución en serie de 3 veces a partir de 30 μM. El compuesto de control Trichostatin A (TSA) se prueba en un IC50 de 10 dosis con una dilución en serie de 3 veces a partir de 5 μM. Los valores de IC50 se extraen mediante el ajuste de curvas de las pendientes dosis/respuesta.
Ensayo celular:[1]
  • Líneas celulares

    Primary cortical neuron of fetal Sprague-Dawley rats (embryonic day 17)

  • Concentraciones

    0-10 μM

  • Tiempo de incubación

    24 hours

  • Método

    Primary cortical neuron cultures are obtained from the cerebral cortex of fetal Sprague-Dawley rats (embryonic day 17) as described previously. All experiments are initiated 24 hours after plating. Under these conditions, the cells are not susceptible to glutamate-mediated excitotoxicity. For cytotoxicity studies, cells are rinsed with warm PBS and then placed in minimum essential medium (Invitrogen) containing 5.5 g/L glucose, 10% fetal calf serum, 2 mM L-glutamine, and 100 μM cystine. Oxidative stress is induced by the addition of the glutamate analogue homocysteate (HCA; 5 mM) to the media. HCA is diluted from 100-fold concentrated solutions that are adjusted to pH 7.5. In combination with HCA, neurons are treated with Tubastatin A at the indicated concentrations. Viability is assessed after 24 hours by MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method.
Estudio en animales:[2]
  • Modelos animales

    Na?ve CD45RBhi CD4+ CD25- cells (1 × 106) from WT or HDAC6-/- mice Are injected i.p. into B6/Rag1-/-mice.

  • Dosificaciones

    0.5 mg/kg

  • Administración

    Tubastatin A is injected i.p. daily.

Referencias

  • https://pubmed.ncbi.nlm.nih.gov/20614936/
  • https://pubmed.ncbi.nlm.nih.gov/21444725/
  • https://pubmed.ncbi.nlm.nih.gov/22174839/
  • https://pubmed.ncbi.nlm.nih.gov/22446682/

Validación de productos por parte del cliente

Control and MEC17 KD macrophages (RAW264.7) were treated with TBSA or DMSO for 12 hours followed by LPS treatment for indicated time. p38 phosphorylation were determined by immuno-blotting.

Datos de [ Nat Commun , 2014 , 5, 3479 ]

<div>Tubastatin A gefitinib-induced apoptosis in NSCLC cells via activation of AKT. H358 cells were treated as described in Figure 4. Representative immunoblots of cleaved caspase-3, AKT and ERK1/2 and of their respective phosphorylated forms are shown. Actin was used as a protein-level control.</div>

Datos de [ Int J Cancer , 2014 , 134(11):2560-71 ]

GH cells were treated with 0.5 μM TSA or the DMSO solvent as indicated. Subsequently, Chromatin immunoprecipitation (ChIP) was performed with antibodies to NF-YB or a pre-immune control antibody. The DNA corresponding to the indicated promoters was quantified by real-time PCR and displayed in relation to the amount of input DNA. Bars indicate the standard error from three independent experiments.

Datos de [ , , Oncotarget, 2016, 7(23):33484-97 ]

Selleck's Tubastatin A Hydrochloride Ha sido citado por 49 Publicaciones

Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity [ Nat Metab, 2022, 4(1):44-59] PubMed: 35039672
HDAC6-dependent deacetylation of AKAP12 dictates its ubiquitination and promotes colon cancer metastasis [ Cancer Lett, 2022, 549:215911] PubMed: 36122629
Sulforaphane reduces obesity by reversing leptin resistance [ Elife, 2022, 11e67368] PubMed: 35323110
Deacetylation mechanism and potential reversal strategy of long QT syndrome on hERG K+ channel under hypoxia [ Biochim Biophys Acta Mol Basis Dis, 2022, 1868(11):166487] PubMed: 35840042
HDAC6 Inhibition Alleviates Ischemia- and Cisplatin-Induced Acute Kidney Injury by Promoting Autophagy [ Cells, 2022, 11(24)3951] PubMed: 36552715
Rutin increases alpha-tubulin acetylation via histone deacetylase 6 inhibition [ Drug Dev Res, 2022, 10.1002/ddr.21927] PubMed: 35266183
Histone Deacetylase 4 Controls Extracellular Matrix Production in Orbital Fibroblasts from Graves' Ophthalmopathy Patients [ Thyroid, 2021, 10.1089/thy.2020.0948] PubMed: 34235979
Requirement of Histone Deacetylase 6 for Interleukin-6 Induced Epithelial-Mesenchymal Transition, Proliferation, and Migration of Peritoneal Mesothelial Cells [ Front Pharmacol, 2021, 12:722638] PubMed: 34526901
Identification of histone deacetylase inhibitors with (arylidene)aminoxy scaffold active in uveal melanoma cell lines [ J Enzyme Inhib Med Chem, 2021, 36(1):34-47] PubMed: 33100043
HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer [ Cancers (Basel), 2021, 13(15)3862] PubMed: 34359763

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