Home PI3K/Akt/mTOR mTOR Inhibitor Torin 2

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Torin 2 mTOR Inhibitor

Kat.-Nr.: S2817

Torin 2 ist ein potenter und selektiver mTOR-Inhibitor mit einem IC50-Wert von 0,25 nM in der p53−/− MEFs-Zelllinie; 800-fach höhere Selektivität für mTOR gegenüber PI3K und verbesserte pharmakokinetische Eigenschaften. Diese Verbindung hemmt ATM/ATR/DNA-PK mit EC50-Werten von 28 nM/35 nM/118 nM in PC3-Zelllinien. Sie verringert die Zellviabilität und induziert Autophagy sowie Apoptosis.
Torin 2 mTOR Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 432.4

Springe zu

Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.75%
99.75

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung PMID
HCT116 Function assay 1 hr Inhibition of mTORC1 in human HCT116 cells assessed as reduction in T389 phosphorylation on RPS6KB1 after 1 hr by Western blot analysis, EC50=0.00025μM 29211480
MOLM13 Antiproliferative assay Antiproliferative activity against human MOLM13 cells by Cell-Titer Glo assay, IC50<0.001μM 30370766
MOLM14 Antiproliferative assay Antiproliferative activity against human MOLM14 cells by Cell-Titer Glo assay, IC50<0.001μM 30370766
MV4-11 Antiproliferative assay Antiproliferative activity against human MV4-11 cells by Cell-Titer Glo assay, IC50<0.001μM 30370766
HEK293T Function assay 20 mins Inhibition of N-terminally FLAG-tagged mTORC1 (unknown origin) expressed in HEK293T cells using S6K1 or Akt1 as substrate after 20 mins by immunoblotting assay, IC50<0.01μM 29211480
HeLa Function assay 20 mins Inhibition of N-terminally FLAG-tagged mTORC2 (unknown origin) expressed in human HeLa cells using S6K1 or Akt1 as substrate after 20 mins by immunoblotting assay, IC50<0.01μM 29211480
RD Antiviral assay 4 days Antiviral activity against Enterovirus A71 infected in human RD cells assessed as reduction in virus-induced cell death incubated for 4 days by CellTiter-Glo luminescence assay, IC50=0.01μM 31082764
HCT116 Function assay 1 hr Inhibition of ATM in human HCT116 cells assessed as after 1 hr by Western blot analysis, EC50=0.028μM 29211480
HCT116 Function assay 1 hr Inhibition of ATR in human HCT116 cells assessed as after 1 hr by Western blot analysis, EC50=0.035μM 29211480
RD Cytotoxicity assay 4 days Cytotoxicity against human RD cells incubated for 4 days by CellTiter-Glo luminescence assay, CC50=0.04μM 31082764
HCT116 Function assay 1 hr Inhibition of DNAPK in human HCT116 cells assessed as after 1 hr by Western blot analysis, EC50=0.118μM 29211480
PC3 Function assay Inhibition of PI3Kalpha in human PC3 cells expressing Akt1 S473D mutant assessed as phosphorylation of Akt Thr308 by immunoblotting, EC50=0.2μM 21322566
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 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
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY 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
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
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD 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
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 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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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht 432.4 Formel

C24H15F3N4O

 Lagerung (Ab dem Eingangsdatum)
CAS-Nr. 1223001-51-1 SDF herunterladen Lagerung von Stammlösungen

Synonyme N/A Smiles C1=CC(=CC(=C1)N2C(=O)C=CC3=CN=C4C=CC(=CC4=C32)C5=CN=C(C=C5)N)C(F)(F)F

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 30 mg/mL (69.38 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse Konzentration Volumen Molekulargewicht
Verdünnungsrechner Molekulargewichtsrechner

In vivo
Charge:

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

mg/kg g μL

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH2O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus (Mechanism of Action)

Targets/IC50/Ki
mTOR
(p53−/− MEFs)
0.25 nM
ATM
(PC3 cells)
28 nM(EC50)
ATR
(PC3 cells)
35 nM(EC50)
DNA-PK
(PC3 cells)
118 nM(EC50)
In vitro

Torin 2 has the same binding mode as PI3Kγ, V882 serves as a hinge binding point and in the inner hydrophobic pocket Y867, D841 and D964 provide three more hydrogen bonds with aminopyridine side chain analogous to Y2225, D2195 and D2357 of mTOR. This compound inhibits mTORC1, thus activates TFEB by promoting its nuclear translocation with EC50 of 1.666 mM. This chemical (< 50 nM) causes a significant reduction in viability of both MZ-CRC-1 and TT cells. It (100 nM) exerts a significant reduction of migration of both MZ-CRC-1 and TT cells.

Kinase-Assay
mTOR- und PI3K-Zellassays
Zelluläre IC50-Werte für mTOR werden unter Verwendung von p53−/− MEFs bestimmt. Zellen werden 1 Stunde lang mit Vehikel oder steigenden Konzentrationen von Torin 2 behandelt und dann lysiert. Die Phosphorylierung von S6K1 Thr-389 wird mittels Immunoblotting unter Verwendung eines phospho-spezifischen Antikörpers überwacht. In der Zwischenzeit werden zelluläre IC50-Werte für PI3Ka basierend auf der Phosphorylierung von Akt Thr-308 in p53−/−/mLST8−/− MEFs oder menschlichen PC3-Zellen, die die S473D-Mutante von Akt1 exprimieren, bestimmt.
In vivo

Torin 2 exhibits >95% pharmacodynamic response and half-time of 11.7 min in the mouse liver microsome stability study. This compound exhibits the best bioavailability (51%), short half-life (0.72 hours) and low clearance(19.6 mL/min/kg) in male Swiss albino mice following intravenous and oral administration. This chemical (20mg/kg) ablates MYCN tumors with reduction in MYCN protein levels and induction of apoptosis in Th-MYCN mice.

Literatur
  • [4] https://pubmed.ncbi.nlm.nih.gov/22789543/
  • [5] https://pubmed.ncbi.nlm.nih.gov/23436801/

Anwendungen (Applications)

Methoden Biomarker Bilder PMID
Western blot p-S6K / S6K / p-AKT / AKT / IRS1 / p-4EBP1 / 4EBP1 / p-GSK3 p-Chk1 / Chk1 / p-Chk2 / Chk2 / p-DNA-PK
S2817-WB1
23436801
Immunofluorescence LC3B
S2817-IF1
23436801
Growth inhibition assay Cell viability
S2817-viability1
24434750