Name: Sapanisertib (MLN0128, INK-128)
Brand: Selleck Chemicals
SKU: S2811
Rating: 5 (129 reviews)

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Contrôle Qualité

Lot : Pureté : 99.94%

99.94

Cibles apparentées	PI3K Akt GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Autre mTOR Inhibiteurs	Torin 1 Torin 2 AZD8055 Ridaforolimus (Deforolimus, MK-8669) Torkinib (PP242) MHY1485 Vistusertib (AZD2014) KU-0063794 OSI-027 WYE-354

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	PMID
U87	Function assay			Inhibition of mTOR in human U87 cells assessed as reduction in p4EBP1 phosphorylation by Western blot method	ChEMBL
U87	Function assay			Inhibition of mTOR in human U87 cells assessed as reduction in pAKT phosphorylation at residue 47 by Western blot method	ChEMBL
PC3	Antiproliferative assay		72 hrs	Antiproliferative activity against human PC3 cells measured after 72 hrs by Alamar blue dye-based fluorescence analysis, EC50 = 0.1 μM.	ChEMBL
SKOV3	Function assay		1 hr	Inhibition of TORC2 in human SKOV3 cells assessed as decrease in PKB/Akt phosphorylation at Ser473 after 1 hr by Western blot analysis	30359003
A2058	Function assay		1 hr	Inhibition of TORC1 in human A2058 cells assessed as decrease in S6K phosphorylation after 1 hr by Western blot analysis	30359003
SKOV3	Function assay		1 hr	Inhibition of TORC1 in human SKOV3 cells assessed as decrease in S6K phosphorylation after 1 hr by Western blot analysis	30359003
SKOV3	Function assay		1 hr	Inhibition of TORC1 in human SKOV3 cells assessed as decrease in S6 phosphorylation at Ser235/236 after 1 hr by Western blot analysis	30359003
SKOV3	Function assay		1 hr	Inhibition of TORC1 in human SKOV3 cells assessed as decrease in 4E-BP1 phosphorylation after 1 hr by Western blot analysis	30359003
A2058	Function assay		1 hr	Inhibition of TORC1 in human A2058 cells assessed as decrease in 4E-BP1 phosphorylation after 1 hr by Western blot analysis	30359003
A2058	Function assay		1 hr	Inhibition of TORC1 in human A2058 cells assessed as decrease in S6 phosphorylation at Ser235/236 after 1 hr by Western blot analysis	30359003
A2058	Function assay		1 hr	Inhibition of TORC2 in human A2058 cells assessed as decrease in PKB/Akt phosphorylation at Ser473 after 1 hr by Western blot analysis	30359003
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 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
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
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 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
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 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
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 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
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 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
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 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
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY 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
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 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
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) 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
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
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
PANC-1	Cell Viability Assay	1-100 nM	72 h	inhibits cell viability dose dependently	24971544
PANC-1	Cell Viability Assay	50 nM	24-96 h	inhibits cell viability time dependently	24971544
MIA PaCa-2	Cell Viability Assay	1-100 nM	72 h	inhibits cell viability dose dependently	24971544
PANC-1	Apoptosis Assay	10-100 nM	72 h	induces apoptosis dose dependently	24971544
PANC-1	Function Assay	10/50 nM	24 h	dramatically inhibits phosphorylation of 4E-BP1-S6K1 (mTORC1 activation indicators) and Akt at Ser 473 (the mTORC2 activation indicator)	24971544
PANC-1	Function Assay	10 nM	72 h	increases LY 188011 sensitivity	24971544
PANC-1	Function Assay	50 nM	48 h	disrupts cell cycle progression	24971544
U87	Function assay			Inhibition of mTOR pS6K in human U87 cells assessed as inhibition of 4EBP1 phosphorylation by Western blot analysis	ChEMBL
U87	Function assay			Inhibition of mTOR in human U87 cells assessed as reduction in pRAS40 phosphorylation by Western blot method	ChEMBL
U87	Function assay			Inhibition of mTOR pS6K in human U87 cells assessed as inhibition of RAS40 phosphorylation by Western blot analysis	ChEMBL
U87	Antitumor assay	0.3 to 3 mg/kg	14 days	Antitumor activity against human U87 cells xenografted in mouse assessed as tumor growth inhibition at 0.3 to 3 mg/kg measured after 14 days	ChEMBL
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Informations chimiques, stockage et stabilité

Poids moléculaire	309.33	Formule	C₁₅H₁₅N₇O	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	1224844-38-5	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	INK 128,TAK-228			Smiles	CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(C=C3)OC(=N4)N)N

Solubilité

In vitro
Lot:

DMSO : 62 mg/mL (200.43 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 2 mg/mL

Water : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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.
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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter dabord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue, lors de lajout précédent, est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Targets/IC₅₀/Ki	mTOR (Cell-free assay) 1.4 nM(Ki) mTOR (Cell-free assay) 1.4 nM(Ki) PI3Kα (Cell-free assay) 219 nM PI3Kγ (Cell-free assay) 221 nM PI3Kδ (Cell-free assay) 230 nM PI3Kβ (Cell-free assay) 5293 nM
In vitro	INK 128 présente une activité d'inhibition enzymatique contre mTOR et une sélectivité plus de 100 fois supérieure aux kinases PI3K. En tant qu'inhibiteur de TORC1/2, INK 128 inhibe à la fois la phosphorylation de S6 et de 4EBP1, les substrats en aval de TORC1, et inhibe sélectivement la phosphorylation d'AKT à Ser473, le substrat en aval de TORC2. De plus, INK 128 montre également de puissants effets inhibiteurs sur les lignées cellulaires résistantes à la rapamycine et aux inhibiteurs pan-PI3K.
In vivo	Dans un modèle de xénogreffe de cancer du sein ZR-75-1, INK 128 montre une efficacité d'inhibition de la croissance tumorale à une dose de 0,3 mg/kg/jour. L'administration orale quotidienne d'INK 128 inhibe l'angiogenèse et la croissance tumorale dans des modèles de multiplexenogreffes.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/20622997/ [2] http://mct.aacrjournals.org/cgi/content/meeting_abstract/8/12_MeetingAbstracts/B148 [3] https://pubmed.ncbi.nlm.nih.gov/22367541/

Applications

Méthodes	Biomarqueurs	Images	PMID
Western blot	p-4EBP1 / 4EBP1 / p-S6 / S6 / p-Akt-S473 / p-Akt-T308 / Akt CD44 / Vimentin c-Jun p-mTOR(Ser2448) / mTOR / p-p70S6K(Thr389) / p70S6K / p-RPS / RPS6 FKBP1 / MARS / CDC25A / TCL1A		25425103
Growth inhibition assay	Cell viability		25425103

Informations sur lessai clinique

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
NCT04250545	Recruiting	Leptomeningeal Neoplasm\|Metastatic Lung Non-Small Cell Carcinoma\|Metastatic Malignant Neoplasm in the Brain\|Recurrent Lung Non-Small Cell Carcinoma\|Stage IV Lung Cancer AJCC v8\|Stage IVA Lung Cancer AJCC v8\|Stage IVB Lung Cancer AJCC v8	National Cancer Institute (NCI)	October 26 2020	Phase 1
NCT02575339	Terminated	Hepatocellular Carcinoma\|Liver Cancer\|HCC	Kathy Miller\|Millennium Pharmaceuticals Inc.\|Big Ten Cancer Research Consortium	July 18 2016	Phase 1\|Phase 2
NCT02719691	Completed	Metastatic Breast Cancer\|Solid Tumors	University of Colorado Denver	May 13 2016	Phase 1
NCT02514824	Completed	Merkel Cell Carcinoma	Dana-Farber Cancer Institute\|Millennium Pharmaceuticals Inc.	October 2015	Phase 1\|Phase 2

Support technique

Instructions de manipulation

Tel: +1-832-582-8158 Ext:3

Si vous avez dautres questions, veuillez laisser un message.

Foire aux questions

Question 1:
What is the recommendation method to formulate it for oral administration?

Réponse :
For oral administration, it can be tried with this vehicle: 30% PEG400+0.5% Tween80 +5% Propylene glycol.

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):

Sapanisertib (MLN0128, INK-128) mTOR inhibiteur

Structure chimique

Poids moléculaire: 309.33