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Wortmannin (SL-2052) PI3K inhibitor

Name: Wortmannin (SL-2052)
Brand: Selleck Chemicals
SKU: S2758
Rating: 5 (340 reviews)

Cat. No.: S2758

Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity.

Wortmannin (SL-2052) PI3K inhibitor Chemical Structure

Estructura química

Peso molecular: 428.43

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Control de calidad (Quality Control)

Lote: Pureza: 99.97%

99.97

Dianas relacionadas	Akt mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Otros PI3K Inhibidores	GDC-0077 (Inavolisib) SAR405 Quercetin (Sophoretin) LY294002 XL147 analogue Tersolisib (STX-478) Buparlisib (BKM120) 740 Y-P (PDGFR 740Y-P) GO-203 TFA Eganelisib (IPI-549)

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

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Formulación	Descripción de la actividad	PMID
Mel-HO	Apoptosis Assay	4/8 μM	24 h		enhances TRAIL-induced apoptosis	24113173
A-375-TS	Apoptosis Assay	4/8 μM	24 h		enhances TRAIL-induced apoptosis	24113173
A-375	Apoptosis Assay	4/8 μM	24 h		enhances TRAIL-induced apoptosis	24113173
Huh7	Function Assay	3 μM	1 h		reduces the virus entry into the cells	24184196
BEL/FU	Function Assay	1 mM	24 h		decreases protein levels of the PI3K/Akt pathway	24232099
HCT 116	Function Assay	100 nM	24 h		attenuates the colonies of the tumor cells with upregulation of Akt1	24297510
HepG2	Function Assay	100 nM	24 h		attenuates the colonies of the tumor cells with upregulation of Akt1	24297510
SW480	Function Assay	150nM	20 h	DMSO	reduces cellular accumulation of β-catenin	24324366
HEK-293	Function Assay	150nM	16 h	DMSO	decreases CRT activity	24324366
5637	Apoptosis Assay	10 μM	40 min		reverses p21WAF1 expression, CDK expression, and cell inhibition induced by fucoidan	24333868
MG-63	Apoptosis Assay	10 µM	12 h		enhances DP-induced apoptosis	24358301
H1975	Function Assay	10 μM	1 h	DMSO	decreases cellular phospho-AKT protein levels	24447935
H520	Function Assay	10 μM	1 h	DMSO	decreases cellular phospho-AKT protein levels	24447935
HepG2	Function Assay	200 nM	0.5 h		attenuates FoxO phosphorylation	24535192
HL-60	Function Assay	0.1 μM	72 h		blocks cell differentiation	24607273
SK-N-LO	Function Assay	100 nM	0.5 h		decreases the stimulant effects of on Akt phosphorylation	24654606
A549	Function Assay	10 μm	16 h	DMSO	modulates the IAV replication and causes retention of NP in the nucleus.	24802111
A549	Growth Inhibition Assay	3 µM	2 h		suppresses Akt and GSK3β activation, S-phase arrest, cell apoptosis and caspase-3 activation	24847863
HepG2	Function Assay	100 nM	0.5 h	DMSO	blocks MA-induced Akt phosphorylation	24863350
MO59J	Apoptosis Assay	10 μM	24 h	DMSO	increases the DSB level induced by or	24953561
MO59K	Apoptosis Assay	10 μM	24 h	DMSO	increases the DSB level induced by or	24953561
MO59J	Cytotoxicity Assay	5 μM	7 d	DMSO	enhances the cytotoxicity of or	24953561
MO59K	Cytotoxicity Assay	5 μM	7 d	DMSO	enhances the cytotoxicity of or	24953561
HT-29	Growth Inhibition Assay	1.5 µM	96 h		decreases cell growth which can be inhibited by KYNA	25012123
MCF7	Function Assay	100 nM	24 h		eliminates E2-induced ARE-Luc activity	25172557
MDA-MB-231	Apoptosis Assay	1 μM	48 h	DMSO	decreases the cell survival treated with 25 μM of F1 or F2	25300932
APRE-19	Apoptosis Assay	5 μM	24 h		abolishes FLZ-mediated pro-survival/anti-apoptosis activity	25329617
HUVECs	Cytotoxicity Assay	100 nM	24 h		attenuates the abrogative effects of calycosin on VRI-induced cytotoxicity	25450186
H1703	Growth Inhibition Assay	2.5 μM	1-4 d	DMSO	enhances cell growth inhibition treatment with	25490383
A459	Growth Inhibition Assay	2.5 μM	1-4 d	DMSO	enhances cell growth inhibition treatment with	25490383
Mel-HO-TS	Apoptosis Assay	4/8 μM	24 h		enhances TRAIL-induced apoptosis	24113173
MeWo	Apoptosis Assay	4/8 μM	24 h		enhances TRAIL-induced apoptosis	24113173
Mel-2a	Apoptosis Assay	4/8 μM	24 h		enhances TRAIL-induced apoptosis	24113173
MDA-MB-231	Function Assay	0–400 nM	4 h		suppresses Akt phosphorylation in a dose-dependent manner	22906259
MDA-MB-231	Function Assay	400 nM	4 h		decreases MMP-9 and IL-8 protein in a dose-dependent manner	22906259
Jurkat	Growth Inhibition Assay	0.25-1.25 μM	24/48 h	DMSO	inhibits cell proliferation in both time- and dose- dependent manner	19757185
Namalwa	Growth Inhibition Assay	0.25-1.25 μM	24/48 h	DMSO	inhibits cell proliferation in both time- and dose- dependent manner	19757185
Jurkat	Apoptosis Assay	0.25-1.25 μM	24/48 h	DMSO	induces cell apoptosis in both time- and dose- dependent manner	19757185
Namalwa	Apoptosis Assay	0.25-1.25 μM	24/48 h	DMSO	induces cell apoptosis in both time- and dose- dependent manner	19757185
K562	Growth Inhibition Assay		24 h		IC50=25±0.14 nM	19662361
SW1990	Function Assay	0.01-1 μM	1 h		inhibits HA-induced Akt phosphorylation	19469020
RT112	Growth Inhibition Assay	10 μM	24 h	DMSO	decreases the proportion of G2/M cells	18787832
MHG-U1	Growth Inhibition Assay	10 μM	24 h	DMSO	decreases the proportion of G2/M cells	18787832
SMMC-7721	Apoptosis Assay	200 nM	24 h		increases CHX-induced apoptosis	17557191
SMMC-7721	Function Assay	200 nM	24 h		up-regulates β1,4GT1 expression	17557191
HeLa	Function Assay	100 nM	1 h		alters the morphology of the transferrin recycling compartment	16890915
MRC5VI	Function Assay	12.5 mM	0.5 h	DMSO	abolishes the Ser473/Thr308 phosphorylation of AktPKB	16227394
AT5BIVA	Function Assay	12.5 mM	0.5 h	DMSO	abolishes the Ser473/Thr308 phosphorylation of AktPKB	16227394
M059J	Function Assay	12.5 mM	0.5 h	DMSO	abolishes the Ser473/Thr308 phosphorylation of AktPKB	16227394
HeLa	Function Assay	12.5 mM	0.5 h	DMSO	abolishes the Ser473/Thr308 phosphorylation of AktPKB	16227394
N2a	Apoptosis Assay	0.1-10 μM	2 h		induces decreased cell viability in a concentration-dependent manner	15842767
Jurkat	Kinase Assay				IC50 of 24 nM	15664519
Sf9	Function assay				Inhibition of human PI3Kalpha expressed in Sf9 cells by fluorescent polarization assay, IC50 = 0.012 μM.	21121631
HeLa	Function assay				Inhibition of AX-7503 binding to recombinant Plk3 expressed in HeLa cells by Western blot, IC50 = 0.049 μM.	17135248
HeLa	Function assay				Binding affinity for DNA dependent protein kinase isolated from HeLa cells; Range is 20-120, Ki = 0.12 μM.	15658870
HeLa	Function assay				Binding affinity for Phosphatidylinositol 3-kinase isolated from HeLa cells; Range is 20-120, Ki = 0.12 μM.	15658870
A549	Function assay				Inhibition of Plk3 in human A549 cells assessed as casein substrate phosphorylation by Western blot, IC50 = 0.22 μM.	17135248
A549	Antiproliferative assay		48 hrs		Antiproliferative activity against human A549 cells after 48 hrs by SRB method, IC50 = 11.4 μM.	18630894
GM00637	Function assay	1 uM			Inhibition of recombinant Plk3 expressed in human GM00637 cells at 1 uM assessed as decrease in p53 serine-20 phosphorylation	17135248
MDA-MB-231	Function assay	1 to 10 uM	24 hrs		Inhibition of PI3K in human MDA-MB-231 cells assessed as inhibition of AKT phosphorylation at 1 to 10 uM after 24 hrs by Western blot analysis	24828286
HeLa	Function assay	100 nM	10 mins		Inhibition of PI3K in human HeLa cells assessed as reduction in EGF-stimulated AKT phosphorylation at S473 at 100 nM preincubated for 10 mins followed by EGF stimulation measured after 5 mins by Western blot analysis	30380865
HeLa	Function assay	100 nM	10 mins		Inhibition of PI3K in human HeLa cells assessed as reduction in EGF-stimulated AKT phosphorylation at T308 at 100 nM preincubated for 10 mins followed by EGF stimulation measured after 5 mins by Western blot analysis	30380865
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	428.43	Fórmula	C₂₃H₂₄O₈	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	19545-26-7	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	KY 12420, SL-2052, BRN 0067676, NSC 627609			Smiles	CC(=O)OC1CC2(C(CCC2=O)C3=C1C4(C(OC(=O)C5=COC(=C54)C3=O)COC)C)C

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 85 mg/mL (198.39 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.
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 (11.67mM)	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.
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	PI3K (Cell-free assay) 3 nM DNA-PK (Cell-free assay) 16 nM ATM (Cell-free assay) 150 nM MLCK (Cell-free assay) 170 nM
In vitro	The inhibition of MLCK by Wortmannin is not affected by calmodulin or peptide substrat, while reduced by high concentration of ATP. This compound directly interacts with the catalytic domain of MLCK and leads to an irreversible loss of the enzyme activity. It has no inhibitory to cAMP-dependent protein kinase, cGMP-dependent protein kinase, and calmodulin-dependent protein kinase II, and has little effect on protein kinase C activity. This inhibitor inhibits N-formylmethionyl-leucylphenylalanine (fMLP)-stimulated PtdInsP3 (phosphatidylinositol 3,4,5-trisphosphate) formation with IC50 of 5 nM and this inhibition is completely abolished when pretreated with 100 nM of this compound in human neutrophils, with increased PtdInsP2 levels and no effects on cellular PtdInsP and PtdIns contents. It could develop oscillatory changes in F-actin content and does not inhibit fMLP-stimulated actin polymerization in neutrophils. This chemical irreversibly inhibits phosphatidylinositol 3-kinase (PI3-kinase) activity with binding to the 110-kDa protein (IC50 of 3 nM) and has no effect PI4-kinase in RBL-2H3 cells. It also inhibits leukotriene release, with no effect on the activation of the tyrosine kinase Lyn. This compound completely abolishes the induced hexose uptake in isolated rat adipocytes at 0.1 μM, without impairing stimulated lipolytic activity. It suppresses induced production of nitric oxide by 50% at 500 nM in human umbilical vein endothelial cells, which is in response to IGF-1. This chemical suppresses DNA double strand break (DSB) repair and has no effect on DSB levels or the kinetics of single strand break (SSB) repair in Chinese hamster ovary cells at 50 μM. It could potentiate ionizing radiation (IR)-induced cytotoxicity with no toxicity by itself. This inhibitor inhibits polo-like kinase (PLK1) activity IC50 of 24 nM in intact G2/M-arrested cells. It increases Toll-like receptor (TLR)-mediated accumulation of IL-6 in human macrophages with EC50 of 50 nM. Meanwhile this compound significantly enhances TLR-mediated inducible nitric-oxide synthase (iNOS) expression and nitrite accumulation in mouse macrphages. It activates the nuclear factor-κB and up-regulates the cytokine mRNA production. This chemical also inhibits Polo-like kinase (PlK) 1 and PlK3, which play important roles in mitosis. Its treatment could lead to a reduction in phosphorylation of p53 on serine 20 induced by DNA damage. It suppresses hyaluronan-induced Akt phosphorylation and cell motility/migration in SW1990 cells.
Ensayo de quinasa	Ensayo de MLCK
Ensayo de quinasa	La actividad de la MLCK se ensaya con un sustrato peptídico (KKRPQRATSNVFS-NH₂) o la cadena ligera de miosina. El sustrato peptídico (24 μM) se fosforila en una mezcla de reacción que contiene 25 mM Tris-HC1 (pH 7.5), 0.5 mg/mL de albúmina sérica bovina, 4 mM de MgCl₂, 0.5 mM de CaCl₂, 2.6 nM de calmodulina, 1.5 nM de MLCK y 400 μM de ATP en un volumen final de 0.25 mL. Después de una preincubación de 10 min a 28 ºC sin ATP, la reacción se inicia mediante la adición de ATP a 28 ºC y se termina mediante la adición de 0.1 mL de ácido acético al 10% (v/v) después de 30 min. La mezcla se analiza mediante cromatografía líquida de alta resolución: columna, Unisil Pack 5C18 4.6 X 150 mm; disolvente, 18% (v/v) de acetonitrilo, 0.1% (v/v) de ácido trifluoroacético en agua; caudal, 1.0 mL/min; temperatura, 40 ºC; detección, absorbancia a 220 nm. El porcentaje de reacción se calcula a partir de la relación de las áreas de los picos de la forma fosforilada respecto a las de la forma no fosforilada. La actividad específica medida bajo las condiciones descritas anteriormente es de 0.81 μmol/min/mg. La cadena ligera de miosina (108 μg/mL) se fosforila en una mezcla de reacción que contiene 25 mM Tris-HC1 (pH 7.5), 0.5 mg/mL de albúmina sérica bovina, 4 mM de MgCl₂, 0.5 mM de CaCl₂, 4.2 nM de calmodulina, 0.92 nM de enzima y 10 μM de [γ-³²P]ATP (100-900 cpm/pmol) en un volumen final de 0.25 mL. Después de una preincubación de 3 min a 30 ºC sin ATP, la reacción se inicia mediante la adición de [γ-³²P]ATP a 30 ºC y se detiene mediante la adición de 0.125 mL de ácido tricloroacético después de 5 min. Los materiales precipitables con ácido se recogen en un filtro de membrana de nitrocelulosa y se lavan con cuatro alícuotas de 1 mL de ácido tricloroacético al 5% (v/v). La radioactividad en el filtro se mide en un fluido de centelleo de tolueno, utilizando un espectrómetro de centelleo líquido Packard Tri-Carb Modelo 4530. La actividad específica medida bajo estas condiciones es de 1.23 μmol/min/mg.
In vivo	Wortmannin inhibits peritoneal metastasis of SW1990 in mice at 1 mg/kg, without any weight loss. This compound inhibits phosphatidylinositide 3-kinase-protein kinase B (PKB)/Akt phosphorylation in both normal tissues (lung, heart and brain homogenates) and tumor tissue in mice, without mortality or acute toxicity at 0.7 mg/kg. Combination with LY188011, this chemical significantly increases apoptosis and inhibit tumor growth in orthotopic tumor, while both monotherapy could not.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/1733924/ [2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1137693/ [3] https://pubmed.ncbi.nlm.nih.gov/7503989/ [4] https://pubmed.ncbi.nlm.nih.gov/8106400/ [5] https://pubmed.ncbi.nlm.nih.gov/8770859/ [6] https://pubmed.ncbi.nlm.nih.gov/8968039/ [7] https://pubmed.ncbi.nlm.nih.gov/15664519/ [8] https://pubmed.ncbi.nlm.nih.gov/16474002/ [9] https://pubmed.ncbi.nlm.nih.gov/17135248/ [10] https://pubmed.ncbi.nlm.nih.gov/19469020/ [11] https://pubmed.ncbi.nlm.nih.gov/19469020/ [12] https://pubmed.ncbi.nlm.nih.gov/9766667/ [13] https://pubmed.ncbi.nlm.nih.gov/35027451/

Aplicaciones (Applications)

Métodos	Biomarcadores	PMID
Western blot	p-AKT / AKT / p-GSK3β / GSK3β / Bcl-xl / Bax / Caspase-3 / Cleaved caspase-3	25344912
Immunofluorescence	DNMT1	24001151
Growth inhibition assay	Cell viability	25344912

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):