Name: GSK461364
Brand: Selleck Chemicals
SKU: S2193
Rating: 5 (32 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.97%

99.97

Dianas relacionadas	CDK HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase
Otros PLK Inhibidores	Volasertib (BI6727) BI 2536 Rigosertib Sodium (ON-01910) Onvansertib (NMS-1286937, NMS-P937) CFI-400945 HMN-214 Ro3280 SBE 13 HCl MLN0905 Centrinone (LCR-263)

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

Líneas celulares	Tipo de ensayo	Tiempo de incubación	Descripción de la actividad	PMID
human MV4-11 cells	Cytotoxicity assay	24 h	Cytotoxicity against human MV4-11 cells after 24 hrs by CellTiter-Blue assay, GI50=0.679 μM	26191363
HEK293T	Antiproliferative assay	72 hrs	Antiproliferative activity against HEK293T cells measured after 72 hrs by CellTiter-Blue assay, IC50=0.001μM	28792760
MDA-MB-231	Antiproliferative assay	72 hrs	Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs by CellTiter-Blue assay, IC50=0.001μM	28792760
MM1S	Antiproliferative assay	72 hrs	Antiproliferative activity against human MM1S cells measured after 72 hrs by CellTiter-Blue assay, IC50=0.001μM	28792760
MDA-MB-23	Function assay	6 hrs	Inhibition of PLK1 in human MDA-MB-23 cells assessed as decrease in TCTP phosphorylation after 6 hrs by Western blot method, IC50<0.1μM	28792760
HEK293T	Function assay	6 hrs	Inhibition of PLK1 in HEK293T cells assessed as decrease in TCTP phosphorylation after 6 hrs by Western blot method, IC50<0.1μM	28792760
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
fibroblast cells	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	543.6	Fórmula	C₂₇H₂₈F₃N₅O₂S	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	929095-18-1	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	GSK461364A			Smiles	CC(C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N

Solubilidad (Solubility)

In vitro
Lote:

Ethanol : 30 mg/mL

DMSO : 10 mg/mL (18.39 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : 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.

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)

Características	Demonstrates >390-fold selectivity for Plk1 relative to Plk2 and Plk3.
Targets/IC₅₀/Ki	PLK1 (Cell-free assay) 2.2 nM(Ki)
In vitro	GSK461364 inhibits cancer cell line proliferation from multiple origins with minimal toxicity in nondividing human cells. RNA silencing of WT p53 increases the antiproliferative activity of this compound. As many cancer therapies tend to be more effective in p53 WT patients, the higher sensitivity of p53-deficient tumors toward this chemical could potentially offer an opportunity to treat tumors that are refractory to other chemotherapies as well as early line therapy for these genotypes. This compound is a thiophene amide that inhibits purified Plk1 enzyme in vitro with a K_i of 2 nM and has >100-fold selectivity for Plk1 compared with Plk2 and Plk3. It is a potent inhibitor of cell proliferation causing 50% growth inhibition (GI50) below 100 nM in most of the cell lines tested with limited toxicity against human nonproliferating cells. Inhibition of cell cycle progression is concentration dependent with initial delay at G2 phase at high concentrations of this agent and arrest at M phase at lower concentrations. Currently, it is in a dose-escalation first-time-in-human trial. Cell lines with mutations in the TP53 gene tended to be more sensitive to this compound, and that inhibiting the p53 response by RNA silencing confers increased sensitivity in some p53 wild-type (WT) cells. Furthermore, these more sensitive cell lines also have increased levels of chromosome instability, a characteristic associated with TP53 mutations. In preclinical testing, this chemical shows antiproliferative activity against multiple (>120) tumor cell lines and potently inhibits the proliferation of greater than 83% and 91% of these cell lines, with IC50 values lower than 50 and 100 nM, respectively.
Ensayo de quinasa	Ensayos enzimáticos
Ensayo de quinasa	Las reacciones de quinasa se realizan en un volumen final de ensayo de 10 μL utilizando el kit de ensayo Z-Lyte (péptido Ser/Thr 16). Brevemente, las reacciones contienen 50 mM HEPES (pH 7.5), 10 mM MgCl₂, 1 mM EGTA, 1 mM DTT, 0.01% Brij 35, 0.01 mg/mL caseína, 200 μM ATP, 200 μM péptido Polo Box (NH₂-MAGPMQS[pT]PLNGAKK-OH) y 6 nM Plk1 recombinante (H6-tev-PLK 1-603). Plk1 se preincubó durante 60 minutos con 0 a 1 μM GSK461364. Las reacciones se inician luego con la adición de 2 μM de péptido. Después de 15 minutos a 23 °C, las reacciones se inactivan y se procesan de acuerdo con el protocolo Z'-Lyte y se leen en un lector de placas EnVision. Los valores de fluorescencia brutos se convierten en concentración de producto formado utilizando estándares de sustrato y producto. Debido a que la potencia de inhibición de este compuesto se observa que varía en función de la concentración de ATP de una manera consistente con un modo de inhibición competitivo de ATP, se determina un límite superior para el K_i para este químico.
In vivo	Cell culture growth inhibition by GSK461364 can be cytostatic or cytotoxic but leads to tumor regression in xenograft tumor models under proper dose scheduling. This compound shows clear antitumor activity in human tumor xenograft models. It shows a dose-dependent mitotic arrest in mouse xenografts, which correlates with effects on tumor growth. Intraperitoneal administration of this chemical causes regression or tumor growth delay in different xenograft models, including Colo205 xenografts. Suppression of Plk1 in vivo by using this agent results in mitotic arrest with aberrant mitotic figures consisting of monopolar or collapsed mitotic spindles.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/19690138/ [2] https://pubmed.ncbi.nlm.nih.gov/20571075/ [3] https://pubmed.ncbi.nlm.nih.gov/21459796/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	p-Myt1 / Myt1 / Plk1		26597303

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
NCT00536835	Completed	Lymphoma Non-Hodgkin	GlaxoSmithKline	August 16 2007	Phase 1

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
I would like to know whether the recommended in vivo formulation will be suitable for i.p. injections of it.

Respuesta:
It is a suspension in 1% DMSO+30% polyethylene glycol+1% Tween 80 at 30mg/ml, and is fine for oral gavage.

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):

GSK461364 PLK inhibitor

Estructura química

Peso molecular: 543.6

Control de calidad (Quality Control)

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

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

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Preguntas frecuentes (Frequently Asked Questions)

GSK461364 PLK inhibitor

Estructura química

Peso molecular: 543.6

Control de calidad (Quality Control)

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

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

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Preguntas frecuentes (Frequently Asked Questions)

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