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Ganetespib (STA-9090) HSP90 Inhibitor

Cat. No.: S1159

Ganetespib (STA-9090) es un inhibidor de HSP90 con una IC50 de 4 nM en células OSA 8, induce la apoptosis de las células OSA mientras que los osteoblastos normales no se ven afectados; metabolito activo de STA-1474. Fase 3.
Ganetespib (STA-9090) HSP Inhibidor Chemical Structure

Estructura química

Peso molecular: 364.4

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.97%
99.97

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
NCI-H1975 Growth Inhibition Assay 72 h IC50=8 nM 22144665
NCI-H1975 Growth Inhibition Assay 48 h IC50=16 nM 22144665
Calu-6 Growth Inhibition Assay IC50=64 nM 23012248
Calu-1 Growth Inhibition Assay IC50=58 nM 23012248
H2122 Growth Inhibition Assay IC50=53 nM 23012248
A549 Growth Inhibition Assay IC50=43 nM 23012248
H358 Growth Inhibition Assay IC50=29 nM 23012248
H1734 Growth Inhibition Assay IC50=28 nM 23012248
H727 Growth Inhibition Assay IC50=28 nM 23012248
COR-L23 Growth Inhibition Assay IC50=22 nM 23012248
H1792 Growth Inhibition Assay IC50=20 nM 23012248
H2009 Growth Inhibition Assay IC50=19 nM 23012248
SK-LU-1 Growth Inhibition Assay IC50=18 nM 23012248
H2212 Growth Inhibition Assay IC50=17 nM 23012248
H441 Growth Inhibition Assay IC50=14 nM 23012248
H2030 Growth Inhibition Assay IC50=12 nM 23012248
H23 Growth Inhibition Assay IC50=11 nM 23012248
HOP-62 Growth Inhibition Assay IC50=11 nM 23012248
IA-LM Growth Inhibition Assay IC50=10 nM 23012248
H460 Growth Inhibition Assay IC50=8 nM 23012248
H157 Growth Inhibition Assay IC50=7 nM 23012248
H1355 Growth Inhibition Assay IC50=5 nM 23012248
VCaP Growth Inhibition Assay IC50=7 nM 23152004
LNCaP Growth Inhibition Assay IC50=8 nM 23152004
Ramos-RA1 Growth Inhibition Assay IC50=7.4 nM 23303741
Karpas-299 Growth Inhibition Assay IC50=9.6 nM 23303741
Kasumi-1 Growth Inhibition Assay IC50=5.8 nM 23303741
CCRF-CEM (2) Growth Inhibition Assay IC50=7.2 nM 23303741
CCRF-CEM (1) Growth Inhibition Assay IC50=12.5 nM 23303741
MOLT-4 Growth Inhibition Assay IC50=10.6 nM 23303741
RS4;11 Growth Inhibition Assay IC50=13.5 nM 23303741
COG-LL-317 Growth Inhibition Assay IC50=4.4 nM 23303741
NALM-6 Growth Inhibition Assay IC50=11.7 nM 23303741
CHLA-136 Growth Inhibition Assay IC50=23.2 nM 23303741
CHLA-90 Growth Inhibition Assay IC50=22.3 nM 23303741
NB-EBc1 Growth Inhibition Assay IC50=16.8 nM 23303741
NB-1643 Growth Inhibition Assay IC50=7.4 nM 23303741
SJ-GBM2 Growth Inhibition Assay IC50=12.9 nM 23303741
CHLA-258 Growth Inhibition Assay IC50=6.4 nM 23303741
CHLA-10 Growth Inhibition Assay IC50=5.7 nM 23303741
CHLA-9 Growth Inhibition Assay IC50=4.6 nM 23303741
TC-71 Growth Inhibition Assay IC50=4.5 nM 23303741
CHLA-266 Growth Inhibition Assay IC50=27.1 nM 23303741
BT-12 Growth Inhibition Assay IC50=14.3 nM 23303741
Rh30 Growth Inhibition Assay IC50=5.6 nM 23303741
Rh18 Growth Inhibition Assay IC50=6.2 nM 23303741
Rh41 Growth Inhibition Assay IC50=10.4 nM 23303741
RD Growth Inhibition Assay IC50=8 nM 23303741
K033 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
M23 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K029 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K028 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K008 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K033 Function Assay 250 nM 24 h induces a modest increase in G1 population 23418523
M23 Function Assay 250 nM 24 h induces G1 and G2/M arrest 23418523
K029 Function Assay 250 nM 24 h induces G1 arrest 23418523
K028 Function Assay 250 nM 24 h induces G2 arrest 23418523
K008 Function Assay 250 nM 24 h induces G2 arrest 23418523
K033 Cell Viability Assay IC50=75.5 nM 23418523
M23 Cell Viability Assay IC50=37.5 nM 23418523
K029 Cell Viability Assay IC50=46 nM 23418523
K028 Cell Viability Assay IC50=84 nM 23418523
K008 Cell Viability Assay IC50=60 nM 23418523
H3122 Cell Viability Assay 0-1000 nM 72 h IC50=10 nM 23533265
H2228 Cell Viability Assay 0-1000 nM 72 h IC50=13 nM 23533265
A1847 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
OVCAR-8 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
OVCAR-5 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
SKOV-3 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
A1847 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
OVCAR-8 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
OVCAR-5 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
H146  Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
GLC4 Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
H82 Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
AC3 Growth Inhibition Assay IC50=25.9 nM 24166505
H1173 Growth Inhibition Assay IC50=12.62 nM 24166505
H792 Growth Inhibition Assay IC50=45.07 nM 24166505
H620 Growth Inhibition Assay IC50=32.67 nM 24166505
N592 Growth Inhibition Assay IC50=14.12 nM 24166505
H526 Growth Inhibition Assay IC50=21.64 nM 24166505
H187 Growth Inhibition Assay IC50=24.99 nM 24166505
H146 Growth Inhibition Assay IC50=28.51 nM 24166505
H128 Growth Inhibition Assay IC50=69.55 nM 24166505
H69 Growth Inhibition Assay IC50=83.36 nM 24166505
GLC4 Growth Inhibition Assay IC50=20.47 nM 24166505
H82 Growth Inhibition Assay IC50=30.27 nM 24166505
MDA-MB-231 Function Assay 100 nM 24 h inhibits the migratory and invasive capacity  24173541
BT-20  Function Assay 100/250 nM 24 h resulted in a dose-dependent destabilization of EGFR, IGF-IR, MET, and CRAF 24173541
MDA-MB-435 Function Assay 100 nM 30 min inhibits accumulation of HIF-1α 24248265
MDA-MB-231 Function Assay 100 nM 30 min inhibits accumulation of HIF-1α 24248265
HCC2998 Growth Inhibition Assay IC50=128 nM 24682747
SK-CO-1 Growth Inhibition Assay IC50=81 nM 24682747
LS-123 Growth Inhibition Assay IC50=73 nM 24682747
SNU-C2B Growth Inhibition Assay IC50=45 nM 24682747
LS-1034 Growth Inhibition Assay IC50=31 nM 24682747
LoVo Growth Inhibition Assay IC50=22 nM 24682747
COLO-678 Growth Inhibition Assay IC50=21 nM 24682747
NCI-H747 Growth Inhibition Assay IC50=17 nM 24682747
COLO-205 Growth Inhibition Assay IC50=14 nM 24682747
HCT 116 Growth Inhibition Assay IC50=14 nM 24682747
HuTu-80 Growth Inhibition Assay IC50=13 nM 24682747
HCT-15 Growth Inhibition Assay IC50=8 nM 24682747
SW620 Growth Inhibition Assay IC50=8 nM 24682747
LS-411 N Growth Inhibition Assay IC50=5 nM 24682747
RKO Growth Inhibition Assay IC50=4 nM 24682747
SW780 Growth Inhibition Assay IC50=3451 nM 24784839
RT4 Growth Inhibition Assay IC50=1733 nM 24784839
TCCSUP Growth Inhibition Assay IC50=142 nM 24784839
MGH-U3 Growth Inhibition Assay IC50=53 nM 24784839
HT-1197 Growth Inhibition Assay IC50=53 nM 24784839
5637 Growth Inhibition Assay IC50=44 nM 24784839
35612 Growth Inhibition Assay IC50=38 nM 24784839
KU-19-19 Growth Inhibition Assay IC50=36 nM 24784839
LB831-BLC Growth Inhibition Assay IC50=34 nM 24784839
UM-UC3 Growth Inhibition Assay IC50=33 nM 24784839
647-V Growth Inhibition Assay IC50=27 nM 24784839
HT-1376 Growth Inhibition Assay IC50=21 nM 24784839
J82 Growth Inhibition Assay IC50=18 nM 24784839
BFTC Growth Inhibition Assay IC50=17 nM 24784839
SCaBER Growth Inhibition Assay IC50=10 nM 24784839
639-V Growth Inhibition Assay IC50=10 nM 24784839
RT112 Growth Inhibition Assay IC50=9 nM 24784839
T24 Growth Inhibition Assay IC50=7 nM 24784839
SW-1710 Growth Inhibition Assay IC50=6 nM 24784839
DSH1 Growth Inhibition Assay IC50=6 nM 24784839
CAL27 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
Detroit562 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
FUDA Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
SCC25 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
HT-29 Function Assay 50nM 24 h DMSO induced G0/G1 arrest 25210794
HCT-116 Function Assay 50nM 24 h DMSO induced G0/G1 arrest 25210794
MGC-803 Function Assay 0.1-1000 nM 24 h induces G2/M cell-cycle arrest 25590805
MKN-28 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
SGC-7901 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
MGC-803 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
MV411 Apoptosis Assay 30/80/150/250 nM 24/48/72 h induces dose dependant induction of apoptosis 25882550
HL60 Apoptosis Assay 30/80/150/250 nM 24/48/72 h induces dose dependant induction of apoptosis 25882550
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 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
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
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 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
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular 364.4 Fórmula

C20H20N4O3

Almacenamiento (Desde la fecha de recepción)
Nº CAS 888216-25-9 Descargar SDF Almacenamiento de soluciones madre

Sinónimos N/A Smiles CC(C)C1=C(C=C(C(=C1)C2=NNC(=O)N2C3=CC4=C(C=C3)N(C=C4)C)O)O

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 40 mg/mL (109.76 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 9 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa Concentración Volumen Peso molecular
Calculadora de Dilución Calculadora de Peso Molecular

In vivo
Lote:

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)

mg/kg g μL

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
HSP90
(OSA 8 cells)
4 nM
In vitro
Las concentraciones inhibitorias al 50% (IC50) para Ganetespib (STA-9090) contra líneas celulares de mastocitos malignos son 10-50 veces menores que las de 17-AAG, lo que indica que la clase de triazolona de inhibidores de HSP90 probablemente exhibe una mayor potencia que los inhibidores basados en geldanamicina. Este compuesto inhibe las líneas celulares MG63 con una IC50 de 43 nM. Se une al dominio de unión a ATP en el N-terminal de Hsp90 y sirve como un potente inhibidor de Hsp90 al causar la degradación de múltiples proteínas cliente oncogénicas de Hsp90, incluyendo HER2/neu, EGFR mutado, Akt, c-Kit, IGF-1R, PDGFRα, Jak1, Jak2, STAT3, STAT5, HIF-1α, CDC2 y c-Met, así como el tumor de Wilms 1. A bajas concentraciones nanomolares, detiene potentemente la proliferación celular e induce la apoptosis en una amplia variedad de líneas celulares de cáncer humano, incluidas muchas líneas celulares resistentes a inhibidores de tirosina quinasa y a tanespimicina. Exhibe una potente citotoxicidad en una variedad de líneas celulares tumorales sólidas y hematológicas, incluidas aquellas que expresan quinasas mutadas que confieren resistencia a inhibidores de tirosina quinasa de moléculas pequeñas. Su tratamiento causó rápidamente la degradación de proteínas cliente de Hsp90 conocidas, exhibe una potencia superior al inhibidor de ansamicina 17-AAG y muestra actividad sostenida incluso con tiempos de exposición cortos. En otro estudio, induce la apoptosis de líneas celulares de mastocitos malignos caninos. Es activo a concentraciones significativamente más bajas para mastocitos malignos caninos C2 y BR con IC50 de 19 y 4 nM, respectivamente, mientras que 17-AAG inhibe mastocitos malignos caninos C2 y BR con IC50 de 958 y 44 nM, respectivamente. Tanto la expresión de Kit WT como mutante se regulan a la baja por 100 nM de este compuesto después de 24 horas en todas las líneas tratadas, incluidas las células C2 y BMCMCs. Sin embargo, no se observan efectos sobre la expresión de PI3K o HSP90 después del tratamiento.
In vivo
La administración de Ganetespib (STA-9090) conduce a una reducción significativa del tamaño del tumor en varios modelos de xenoinjertos tumorales en ratones y parece ser menos tóxica. Además, este compuesto demostró una mejor penetración tumoral en comparación con tanespimicina. Inhibe el crecimiento tumoral in vivo tanto en modelos de xenoinjertos de mastocitos malignos como de OSA. Ganetespib inhibe significativamente el crecimiento tumoral cuando se dosifica con dos ciclos repetidos de 25 mg/kg/día durante 3 días, con un valor de %T/C de 18. Es bien tolerado, con los grupos vehículo y Ganetespib presentando cambios de peso corporal promedio con respecto al inicio del estudio de +0.3% y -8.1% en el día 17, respectivamente.
Referencias
  • [4] https://pubmed.ncbi.nlm.nih.gov/18657349/

Aplicaciones (Applications)

Métodos Biomarcadores Imágenes PMID
Western blot EGFR / c-Met / IGF-1Rβ/ Akt / p-Akt / ERK / p-ERK p27(Kip1) / p21 (Cip1) / Cyclin D1 / Cyclin E / Cyclin B1 / CDK1 / CDK2 / CDK4 Survivin / Bcl-2 / Bcl-xl / Mcl-1 B-RAF / C-RAF / N-RAS HER2 / p-STAT3 / BIM CDK1 / Cyclin D1 / Cyclin B1 / p27 c-PARP / c-caspase 3 / caspase 8 / c-caspase 8 / caspase 9 / c-caspase 9 ErbB2 / pErbB2 / Src / pSrc / mTOR / pmTOR / Bad / pBad / GSK3 / pGSK3 Wee1 / p-Wee1 / Chk1 / p-Chk1
S1159-WB1
23418523
Growth inhibition assay Cell viability
S1159-viability1
23418523

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
NCT02192541 Terminated
Neoplasms
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
December 2 2014 Phase 1
NCT02008877 Completed
Malignant Peripheral Nerve Sheath Tumors (MPNST)|Sarcoma
Sarcoma Alliance for Research through Collaboration|Synta Pharmaceuticals Corp.|United States Department of Defense
December 2013 Phase 1|Phase 2

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
Does this inhibitor inhibit both isoforms of HSP90?

Respuesta:
We don't have the information now and it is not very clear in the literature either. From following two references, it indicates that it might be specific to the alpha form “It binds to the ATP binding site of Hsp90 alpha with a Kd of 110 nM” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477583/