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TIC10 (ONC201) Akt Inhibidor

Name: TIC10 (ONC201)
Brand: Selleck Chemicals
SKU: S7963
Rating: 5 (17 reviews)

Cat. No.: S7963

TIC10 (ONC201) inactiva Akt y ERK para inducir el TNF-related apoptosis-inducing ligand (TRAIL) a través de Foxo3a, posee propiedades farmacológicas superiores: entrega a través de la barrera hematoencefálica, estabilidad superior y farmacocinética mejorada. Fase 1/2.

TIC10 (ONC201) Akt Inhibidor Chemical Structure

Estructura química

Peso molecular: 386.49

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.97%

99.97

Dianas relacionadas	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Otros Akt Inhibidores	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Ipatasertib (GDC-0068) Perifosine GSK690693 Triciribine (API-2) Afuresertib (GSK2110183) CCT128930 A-674563 HCl

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

Peso molecular	386.49	Fórmula	C₂₄H₂₆N₄O	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	1616632-77-9	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	Dordaviprone			Smiles	CC1=CC=CC=C1CN2C(=O)C3=C(CCN(C3)CC4=CC=CC=C4)N5C2=NCC5

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 77 mg/mL (199.22 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 77 mg/mL

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.
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.	3.850mg/ml (9.96mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 77 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; 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	Akt ERK
In vitro	In a p53-independent manner, TIC10 (ONC201) causes a dose-dependent increase in TRAIL mRNA and induces TRAIL protein localization on the cell surface of several cancer cell lines. It has broad-spectrum activity against multiple malignancies in vitro and induces an increase in sub-G1 DNA content suggestive of cell death in TRAIL-sensitive HCT116 p53−/− cells, but does not alter the cell cycle profiles of normal fibroblasts at equivalent doses. This compound decreases the clonogenic survival of cancer cell lines and spares normal fibroblasts. It increases the percentage of sub-G1 DNA in cancer cells in a p53-independent and Bax-dependent manner, as previously reported for TRAIL-mediated apoptosis. TIC10-induced TRAIL up-regulation is Foxo3a-dependent, which also up-regulates TRAIL death receptor DR5 among other targets, potentially allowing for sensitization of some TRAIL-resistant tumor cells. The agent inactivates kinases Akt and extracellular signal–regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. It is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.
In vivo	In the HCT116 p53^−/− xenograft, treatment with TIC10 (ONC201) and TRAIL causes tumor regression to a comparable extent when both are administered as multiple doses. It also induces regression of MDA-MB-231 human triple-negative breast cancer xenografts, whereas TRAIL-treated tumors progressed. In DLD-1 colon cancer xenografts, this compound induces tumor stasis at 1 week after treatment, whereas TRAIL-treated tumors progress after a single dose. A single dose of it also induces a sustained regression of the SW480 xenograft and is equally effective when delivered by intraperitoneal or oral route, suggesting favorable oral bioavailability. It causes tumor-specific cell death by TRAIL-mediated direct and bystander effects and is an effective antitumor agent against orthotopic human glioblastoma multiforme tumors.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/23390247/ [2] https://pubmed.ncbi.nlm.nih.gov/31021596/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	Cleaved PARP / CC3 ATF4 / ATF3 p-GCN2 / GCN2 / p-eIF2a / eIF2a p-p70S6K / p-S6 / p-4EBP1 / 4EBP1 / p-HSF1 / HSF1		29588331
Growth inhibition assay	Cell viability		29588330

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
NCT04629209	Withdrawn	Glioblastoma	Masonic Cancer Center University of Minnesota\|University of Minnesota	June 28 2024	Phase 2
NCT06012929	Not yet recruiting	Meningioma\|Refractory Meningioma\|Relapsed Meningioma	University of Nebraska\|Chimerix	April 2024	Phase 1
NCT05476939	Recruiting	Diffuse Intrinsic Pontine Glioma\|Diffuse Midline Glioma H3 K27M-Mutant	Gustave Roussy Cancer Campus Grand Paris\|Chimerix\|Innovative Therapies For Children with Cancer Consortium	September 29 2022	Phase 3

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