solo para uso en investigación
Cat. No.: S1092
| Dianas relacionadas | HDAC PARP DNA-PK WRN DNA/RNA Synthesis Topoisomerase PPAR Sirtuin Casein Kinase eIF |
|---|---|
| Otros ATM/ATR Inhibidores | Ceralasertib (AZD6738) AZD1390 Berzosertib (VE-822) Lartesertib (M4076) Camonsertib (RP-3500) KU-60019 VE-821 AZ20 AZD0156 Mirin |
| Líneas celulares | Tipo de ensayo | Concentración | Tiempo de incubación | Formulación | Descripción de la actividad | PMID |
|---|---|---|---|---|---|---|
| DU-145 | Growth Inhibition Assay | IC50=3.27352 μM | SANGER | |||
| HuO-3N1 | Growth Inhibition Assay | IC50=4.17142 μM | SANGER | |||
| LAMA-84 | Growth Inhibition Assay | IC50=4.58465 μM | SANGER | |||
| CAL-72 | Growth Inhibition Assay | IC50=5.48084 μM | SANGER | |||
| LoVo | Growth Inhibition Assay | IC50=6.93239 μM | SANGER | |||
| HH | Growth Inhibition Assay | IC50=8.27671 μM | SANGER | |||
| SK-MEL-3 | Growth Inhibition Assay | IC50=8.28575 μM | SANGER | |||
| KM12 | Growth Inhibition Assay | IC50=9.21142 μM | SANGER | |||
| NCI-H1437 | Growth Inhibition Assay | IC50=9.8097 μM | SANGER | |||
| NCI-H1838 | Growth Inhibition Assay | IC50=11.1865 μM | SANGER | |||
| J-RT3-T3-5 | Growth Inhibition Assay | IC50=11.2417 μM | SANGER | |||
| GOTO | Growth Inhibition Assay | IC50=11.6996 μM | SANGER | |||
| LB2241-RCC | Growth Inhibition Assay | IC50=11.7186 μM | SANGER | |||
| ES7 | Growth Inhibition Assay | IC50=11.788 μM | SANGER | |||
| KP-N-YS | Growth Inhibition Assay | IC50=12.6354 μM | SANGER | |||
| CAL-12T | Growth Inhibition Assay | IC50=13.617 μM | SANGER | |||
| COLO-684 | Growth Inhibition Assay | IC50=14.1569 μM | SANGER | |||
| DOK | Growth Inhibition Assay | IC50=15.3329 μM | SANGER | |||
| Hs-578-T | Growth Inhibition Assay | IC50=15.4182 μM | SANGER | |||
| D-423MG | Growth Inhibition Assay | IC50=15.5236 μM | SANGER | |||
| DBTRG-05MG | Growth Inhibition Assay | IC50=15.6111 μM | SANGER | |||
| VM-CUB-1 | Growth Inhibition Assay | IC50=15.9849 μM | SANGER | |||
| KG-1 | Growth Inhibition Assay | IC50=16.0996 μM | SANGER | |||
| 8305C | Growth Inhibition Assay | IC50=16.1889 μM | SANGER | |||
| HuH-7 | Growth Inhibition Assay | IC50=16.2674 μM | SANGER | |||
| LXF-289 | Growth Inhibition Assay | IC50=16.2747 μM | SANGER | |||
| NCI-H1793 | Growth Inhibition Assay | IC50=16.4712 μM | SANGER | |||
| ChaGo-K-1 | Growth Inhibition Assay | IC50=16.6568 μM | SANGER | |||
| GCIY | Growth Inhibition Assay | IC50=16.7905 μM | SANGER | |||
| SK-MEL-28 | Growth Inhibition Assay | IC50=17.0475 μM | SANGER | |||
| NCI-SNU-1 | Growth Inhibition Assay | IC50=17.1269 μM | SANGER | |||
| CTB-1 | Growth Inhibition Assay | IC50=17.2259 μM | SANGER | |||
| NCI-H82 | Growth Inhibition Assay | IC50=17.4573 μM | SANGER | |||
| HCC2998 | Growth Inhibition Assay | IC50=17.6733 μM | SANGER | |||
| NCI-H2030 | Growth Inhibition Assay | IC50=18.1997 μM | SANGER | |||
| HuP-T3 | Growth Inhibition Assay | IC50=18.5888 μM | SANGER | |||
| 697 | Growth Inhibition Assay | IC50=19.0201 μM | SANGER | |||
| MLMA | Growth Inhibition Assay | IC50=19.0557 μM | SANGER | |||
| HCC70 | Growth Inhibition Assay | IC50=19.489 μM | SANGER | |||
| A704 | Growth Inhibition Assay | IC50=19.8305 μM | SANGER | |||
| D-283MED | Growth Inhibition Assay | IC50=20.5339 μM | SANGER | |||
| U031 | Growth Inhibition Assay | IC50=21.1489 μM | SANGER | |||
| HSC-3 | Growth Inhibition Assay | IC50=21.1835 μM | SANGER | |||
| JVM-3 | Growth Inhibition Assay | IC50=22.506 μM | SANGER | |||
| Mewo | Growth Inhibition Assay | IC50=22.5073 μM | SANGER | |||
| YH-13 | Growth Inhibition Assay | IC50=22.5123 μM | SANGER | |||
| LB1047-RCC | Growth Inhibition Assay | IC50=22.5879 μM | SANGER | |||
| HCC2157 | Growth Inhibition Assay | IC50=22.8054 μM | SANGER | |||
| SNU-449 | Growth Inhibition Assay | IC50=22.8748 μM | SANGER | |||
| Ramos-2G6-4C10 | Growth Inhibition Assay | IC50=22.96 μM | SANGER | |||
| CHL-1 | Growth Inhibition Assay | IC50=23.7292 μM | SANGER | |||
| SK-MEL-30 | Growth Inhibition Assay | IC50=24.4662 μM | SANGER | |||
| PANC-08-13 | Growth Inhibition Assay | IC50=25.0938 μM | SANGER | |||
| QIMR-WIL | Growth Inhibition Assay | IC50=25.1858 μM | SANGER | |||
| BFTC-905 | Growth Inhibition Assay | IC50=25.5944 μM | SANGER | |||
| GI-1 | Growth Inhibition Assay | IC50=25.7055 μM | SANGER | |||
| MDA-MB-415 | Growth Inhibition Assay | IC50=26.5033 μM | SANGER | |||
| GT3TKB | Growth Inhibition Assay | IC50=26.5342 μM | SANGER | |||
| DEL | Growth Inhibition Assay | IC50=26.8356 μM | SANGER | |||
| KOSC-2 | Growth Inhibition Assay | IC50=26.9075 μM | SANGER | |||
| RVH-421 | Growth Inhibition Assay | IC50=27.2921 μM | SANGER | |||
| EW-13 | Growth Inhibition Assay | IC50=27.4308 μM | SANGER | |||
| 639-V | Growth Inhibition Assay | IC50=27.5119 μM | SANGER | |||
| A2780 | Growth Inhibition Assay | IC50=27.641 μM | SANGER | |||
| SW982 | Growth Inhibition Assay | IC50=27.9052 μM | SANGER | |||
| SW1710 | Growth Inhibition Assay | IC50=28.0981 μM | SANGER | |||
| HCC1569 | Growth Inhibition Assay | IC50=28.4897 μM | SANGER | |||
| MV-4-11 | Growth Inhibition Assay | IC50=28.5735 μM | SANGER | |||
| BHT-101 | Growth Inhibition Assay | IC50=28.6572 μM | SANGER | |||
| Ca9-22 | Growth Inhibition Assay | IC50=28.714 μM | SANGER | |||
| HAL-01 | Growth Inhibition Assay | IC50=28.7615 μM | SANGER | |||
| D-263MG | Growth Inhibition Assay | IC50=29.344 μM | SANGER | |||
| NEC8 | Growth Inhibition Assay | IC50=29.5548 μM | SANGER | |||
| EKVX | Growth Inhibition Assay | IC50=31.5847 μM | SANGER | |||
| EM-2 | Growth Inhibition Assay | IC50=31.6304 μM | SANGER | |||
| MFM-223 | Growth Inhibition Assay | IC50=31.8098 μM | SANGER | |||
| SK-PN-DW | Growth Inhibition Assay | IC50=32.1406 μM | SANGER | |||
| HuO9 | Growth Inhibition Assay | IC50=32.5282 μM | SANGER | |||
| MHH-PREB-1 | Growth Inhibition Assay | IC50=32.6234 μM | SANGER | |||
| OVCAR-4 | Growth Inhibition Assay | IC50=32.8363 μM | SANGER | |||
| NCI-H1648 | Growth Inhibition Assay | IC50=32.8651 μM | SANGER | |||
| MKN1 | Growth Inhibition Assay | IC50=34.1101 μM | SANGER | |||
| KYSE-450 | Growth Inhibition Assay | IC50=34.6444 μM | SANGER | |||
| ES8 | Growth Inhibition Assay | IC50=34.8975 μM | SANGER | |||
| MS-1 | Growth Inhibition Assay | IC50=34.9554 μM | SANGER | |||
| HOP-92 | Growth Inhibition Assay | IC50=35.9277 μM | SANGER | |||
| SKG-IIIa | Growth Inhibition Assay | IC50=36.2561 μM | SANGER | |||
| TE-11 | Growth Inhibition Assay | IC50=36.5243 μM | SANGER | |||
| SK-NEP-1 | Growth Inhibition Assay | IC50=37.6744 μM | SANGER | |||
| DB | Growth Inhibition Assay | IC50=37.9185 μM | SANGER | |||
| IA-LM | Growth Inhibition Assay | IC50=38.0239 μM | SANGER | |||
| COLO-829 | Growth Inhibition Assay | IC50=38.4159 μM | SANGER | |||
| TGBC11TKB | Growth Inhibition Assay | IC50=39.1408 μM | SANGER | |||
| CAL-51 | Growth Inhibition Assay | IC50=40.0612 μM | SANGER | |||
| NCI-H2228 | Growth Inhibition Assay | IC50=40.3662 μM | SANGER | |||
| C32 | Growth Inhibition Assay | IC50=40.4024 μM | SANGER | |||
| KU-19-19 | Growth Inhibition Assay | IC50=40.7683 μM | SANGER | |||
| KNS-62 | Growth Inhibition Assay | IC50=40.8381 μM | SANGER | |||
| FADU | Growth Inhibition Assay | IC50=41.2502 μM | SANGER | |||
| CAL-33 | Growth Inhibition Assay | IC50=42.6749 μM | SANGER | |||
| CHP-134 | Growth Inhibition Assay | IC50=42.8496 μM | SANGER | |||
| HDLM-2 | Growth Inhibition Assay | IC50=42.9084 μM | SANGER | |||
| NBsusSR | Growth Inhibition Assay | IC50=43.0725 μM | SANGER | |||
| SW954 | Growth Inhibition Assay | IC50=43.1053 μM | SANGER | |||
| HCC1806 | Growth Inhibition Assay | IC50=43.411 μM | SANGER | |||
| VMRC-RCZ | Growth Inhibition Assay | IC50=43.4586 μM | SANGER | |||
| A549 | Growth Inhibition Assay | IC50=43.931 μM | SANGER | |||
| NKM-1 | Growth Inhibition Assay | IC50=43.9558 μM | SANGER | |||
| DMS-273 | Growth Inhibition Assay | IC50=44.7567 μM | SANGER | |||
| TYK-nu | Growth Inhibition Assay | IC50=45.1234 μM | SANGER | |||
| KALS-1 | Growth Inhibition Assay | IC50=45.146 μM | SANGER | |||
| A101D | Growth Inhibition Assay | IC50=45.4456 μM | SANGER | |||
| G-361 | Growth Inhibition Assay | IC50=46.2138 μM | SANGER | |||
| KARPAS-299 | Growth Inhibition Assay | IC50=46.3516 μM | SANGER | |||
| RS4-11 | Growth Inhibition Assay | IC50=46.542 μM | SANGER | |||
| HT-1376 | Growth Inhibition Assay | IC50=46.7426 μM | SANGER | |||
| SK-N-AS | Growth Inhibition Assay | IC50=46.7822 μM | SANGER | |||
| MG-63 | Growth Inhibition Assay | IC50=46.9036 μM | SANGER | |||
| EPLC-272H | Growth Inhibition Assay | IC50=46.9503 μM | SANGER | |||
| BALL-1 | Growth Inhibition Assay | IC50=47.832 μM | SANGER | |||
| LCLC-97TM1 | Growth Inhibition Assay | IC50=48.202 μM | SANGER | |||
| HO-1-N-1 | Growth Inhibition Assay | IC50=48.9676 μM | SANGER | |||
| MFE-280 | Growth Inhibition Assay | IC50=49.4617 μM | SANGER | |||
| NCI-H526 | Growth Inhibition Assay | IC50=49.8163 μM | SANGER | |||
| D-566MG | Growth Inhibition Assay | IC50=49.9096 μM | SANGER | |||
| BB30-HNC | Growth Inhibition Assay | IC50=49.9498 μM | SANGER | |||
| SK-N-DZ | Growth Inhibition Assay | IC50=50.0481 μM | SANGER | |||
| HepG2 | Growth Inhibition Assay | 10 μM | 24 h | blocks SC-III3-induced S phase arrest | 25527123 | |
| HepG2 | Function Assay | 10 μM | 24 h | suppresses the phosphorylations of ATM on Ser1981, Chk1 on Ser345, Chk2 on Thr68, and Cdk2 on Tyr15 induced by SC-III3 | 25527123 | |
| KATO III | Growth Inhibition Assay | 2.5/5/7.5 μM | DMSO | enhances the toxicity of olaparib | 24841718 | |
| hTCEpi | Growth Inhibition Assay | 10 μM | DMSO | prevents the cytopathic effect of HSV-1 | 24370835 | |
| MCF10A | Growth Inhibition Assay | 10 μM | 24 h | DMSO | potentiates the cytotoxicity of GA | 24150595 |
| HL-60 | Function Assay | 10 μM | 0.5 h | DMSO | reduces phosphorylation of Chk2 | 23934411 |
| MCF-7 | Growth Inhibition Assay | 1-100μM | 24 h | FBS | inhibits the cell proliferation | 23185347 |
| HeLa | Growth Inhibition Assay | 1-100μM | 24 h | FBS | inhibits the cell proliferation | 23185347 |
| SH-SY5Y | Function Assay | 10 μM | 24 h | inhibits clioquinol-induced phosphorylation of p53 | 22627294 | |
| IMR-32 | Function Assay | 10 μM | 24 h | inhibits clioquinol-induced phosphorylation of p53 | 22627294 | |
| A549 | Function Assay | 10 μM | 1 h | suppresses Nano-Co-induced p53 accumulation | 22559321 | |
| T47D | Function Assay | 20 mM | 24 h | DMSO | prevents IR-induced degradation of IκBα | 21144805 |
| A29 MEF | Function Assay | 10 μM | 1h | blocks the phosphorylation of Akt at Ser473 | 20053781 | |
| MDA-MB-453 | Growth Inhibition Assay | 5-40 μM | 72 h | IC50 of 10 μM | 20053781 | |
| PC-3 | Growth Inhibition Assay | 5-40 μM | 72 h | IC50 of 10 μM | 20053781 | |
| U2OS | Function assay | Inhibition of ATM in human U2OS cells assessed as inhibition of p53 phosphorylation at Ser15 residue, IC50 = 0.25 μM. | 26632965 | |||
| MCF7 | Function assay | 1 hr | Inhibition of ATM kinase in human MCF7 cells after 1 hr by immunofluorescence assay, IC50 = 0.3 μM. | 26632965 | ||
| BJ | Function assay | 10 uM | 10 days | Suppression of senescence in human BJ cells assessed as increase in cell number at 10 uM after 10 days by senescence reversal assay | 16767085 | |
| BJ | Function assay | 10 uM | 10 days | Inhibition of ataxia telangiectasia-mutated in human BJ cells assessed as increase in cell number at 10 uM after 10 days by senescence reversal assay | 16767085 | |
| MCF7 | Function assay | 10 uM | 10 mins | Sensitization of infrared-induced DNA damage in human MCF7 cells assessed as reduction in colony formation at 10 uM pretreated for 10 mins followed by irradiation for 4 hrs measured after 10 days by crystal violet staining analysis | 26632965 | |
| 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 | |||
| Haga clic para ver más datos experimentales de líneas celulares | ||||||
| Peso molecular | 395.49 | Fórmula | C21H17NO3S2 |
Almacenamiento (Desde la fecha de recepción) | |
|---|---|---|---|---|---|
| Nº CAS | 587871-26-9 | Descargar SDF | Almacenamiento de soluciones madre |
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| Sinónimos | ATM Kinase Inhibitor | Smiles | C1COCCN1C2=CC(=O)C=C(O2)C3=C4C(=CC=C3)SC5=CC=CC=C5S4 | ||
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In vitro |
DMSO
: 39 mg/mL
(98.61 mM)
Water : Insoluble Ethanol : Insoluble |
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In vivo |
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Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)
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.)
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.
| Targets/IC50/Ki |
ATM
(Cell-free assay) 12.9 nM
|
|---|---|
| In vitro |
KU-55933 inhibe DNA-PK y PI3K con IC50 de 2,5 μM y 16,6 μM, respectivamente. Además, este compuesto también previene la actividad de mTOR con una IC50 de 9,3 μM. Es activo a nivel celular en la ablación de un evento de fosforilación dependiente de ATM bien caracterizado. Este químico tiene un efecto dosis-dependiente en la inhibición de este evento de fosforilación dependiente de ATM con una IC50 de 300 nM. KU-58050 no previene la fosforilación de la serina 15 de p53 dependiente de ATM hasta una dosis de 30 μM. La adición de este compuesto no tiene efectos apreciables sobre la fosforilación inducida por UV de H2AX en la serina 139, NBS1 en la serina 343, CHK1 en la serina 345 y SMC1 en la serina 966. En marcado contraste con las respuestas a los UV, ablaciona la fosforilación inducida por radiación ionizante de estos substratos de ATM. Este químico sensibiliza las células HeLa a un rango de dosis de radiación ionizante. Inhibe la fosforilación de Akt inducida por factores de crecimiento en células cancerosas. Este compuesto suprime la proliferación de células cancerosas. Además, la supresión de ATM por este químico mejora la supervivencia, probablemente a través de la prevención de la activación posterior de TAp63α.
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| Ensayo de quinasa |
Ensayos de enzimas purificadas
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La ATM para usar en el ensayo in vitro se obtiene de un extracto nuclear de HeLa por inmunoprecipitación con antisuero policlonal de conejo producido contra los 400 aminoácidos COOH-terminales de ATM en un tampón que contiene 25 mM HEPES (pH 7,4), 2 mM MgCl2, 250 mM KCl, 500 μM EDTA, 100 μM Na3VO4, 10% v/v glicerol y 0,1% v/v Igepal. Los complejos ATM-anticuerpo se aíslan del extracto nuclear incubando con perlas de proteína A-Sepharose durante 1 hora y luego centrifugando para recuperar las perlas. En el pocillo de una placa de 96 pocillos, las perlas de Sepharose que contienen ATM se incuban con 1 μg de sustrato glutatión S-transferasa–p53N66 (66 aminoácidos NH2-terminales de p53 fusionados a glutatión S-transferasa) en tampón de ensayo de ATM [25 mM HEPES (pH 7,4), 75 mM NaCl, 3 mM MgCl2, 2 mM MnCl2, 50 μM Na3VO4, 500 μM DTT y 5% v/v glicerol] a 37 °C en presencia o ausencia de este compuesto. Después de 10 minutos con agitación suave, se añade ATP a una concentración final de 50 μM y la reacción continúa a 37 °C durante 1 hora adicional. La placa se centrifuga a 250 × g durante 10 minutos (4 °C) para eliminar las perlas que contienen ATM, y el sobrenadante se retira y se transfiere a una placa opaca blanca de 96 pocillos y se incuba a temperatura ambiente durante 1,5 horas para permitir la unión de la glutatión S-transferasa-p53N66. Esta placa se lava luego con PBS, se seca con papel secante y se analiza mediante una técnica ELISA estándar con un anticuerpo p53 fosfo-serina 15. La detección del sustrato glutatión S-transferasa-p53N66 fosforilado se realiza en combinación con un anticuerpo secundario de cabra antimouse conjugado con peroxidasa de rábano. Se utiliza una solución de quimioluminiscencia mejorada para producir una señal y se lleva a cabo la detección quimioluminiscente.
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| In vivo |
La supresión de la activación de STAT3 dependiente de ATM por KU-55933 mejora la apoptosis mediada por TRAIL a través de la regulación positiva de la expresión de DR5 en la superficie, mientras que la supresión de STAT3 y NF-κB parece estar implicada en la regulación negativa de cFLIP acompañada de un aumento adicional en los niveles apoptóticos. Este compuesto afecta la apoptosis mediada por TRAIL más fuertemente que el inhibidor de JAK2, AG490, o la sobreexpresión de STAT3β.
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Referencias |
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| Métodos | Biomarcadores | Imágenes | PMID |
|---|---|---|---|
| Western blot |