Nur für die Forschung bestimmt

Torkinib (PP242) mTOR Inhibitor

Name: Torkinib (PP242)
Brand: Selleck Chemicals
SKU: S2218
Rating: 5 (109 reviews)

Kat.-Nr.: S2218

Torkinib (PP242) ist ein selektiver mTOR-Inhibitor mit einer IC50 von 8 nM in zellfreien Assays; diese Verbindung zielt auf beide mTOR-Komplexe mit einer mehr als 10- bzw. 100-fachen Selektivität für mTOR gegenüber PI3Kδ bzw. PI3Kα/β/γ. Es induziert Mitophagy und Apoptosis.

Torkinib (PP242) mTOR Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 308.34

Springen zu

Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.50%

99.50

Verwandte Targets	PI3K Akt GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PI4K PP2A
Andere mTOR Inhibitors	Torin 1 Torin 2 AZD8055 Ridaforolimus (Deforolimus, MK-8669) Sapanisertib (MLN0128, INK-128) MHY1485 Vistusertib (AZD2014) KU-0063794 OSI-027 3BDO

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

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Formulierung	Aktivitätsbeschreibung
HT-p21	Function Assay	50-1250 nM	24 h	DMSO	inhibits phosphorylation of S6 kinase (target of mTORC1) and its downstream target phospho-S6
U87vIII	Function Assay	0.04-2.5 μM	24 h		inhibits mTORC1 and mTORC2 activities
U87vIII	Function Assay	2.5/5 μM	12 h		inhibits gap closing in a dose-dependent manner
PC12	Function Assay	40 nM			induces lysosomal biogenesis and alleviated α-SYN accumulation
3T3-L1	Function Assay	15 μM	4 h		suppresses expression of the Egr1 protein
Rh30	Function Assay	1 μM	2 h		inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt
HT29	Function Assay	1 μM	2 h		inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt
Rh30	Function Assay	1 μM	2 h		suppresses the basal or IGF-1-stimulated cell adhesion
HT29	Function Assay	1 μM	2 h		suppresses the basal or IGF-1-stimulated cell adhesion
U87	Growth Inhibition Assay	25 nM	24 h		increases DUSP10 knocked-down induced cell inhibition
AGS	Cell Viability Assay	0-1000 nM	24/48 h	DMSO	decreases cell viability in time and dose dependent manner
MKN45	Cell Viability Assay	0-1000 nM	24/48 h	DMSO	decreases cell viability in time and dose dependent manner
MKN28	Cell Viability Assay	0-1000 nM	24/48 h	DMSO	decreases cell viability in time and dose dependent manner
KATO3	Cell Viability Assay	0-1000 nM	24/48 h	DMSO	decreases cell viability in time and dose dependent manner
SGC7901	Cell Viability Assay	0-1000 nM	24/48 h	DMSO	decreases cell viability in time and dose dependent manner
N87	Cell Viability Assay	0-1000 nM	24/48 h	DMSO	decreases cell viability in time and dose dependent manner
HMEC	Cell Viability Assay	0-1000 nM	24/48 h	DMSO	decreases cell viability in time and dose dependent manner
HUVEC	Cell Viability Assay	0-1000 nM	24/48 h	DMSO	decreases cell viability in time and dose dependent manner
MG63	Function Assay	50-1000 nM	0.5 h		dose dependently (50–1000 nM) inhibits phosphorylation of Akt
U2OS	Function Assay	50-1000 nM	0.5 h		dose dependently (50–1000 nM) inhibits phosphorylation of Akt
Saos-2	Function Assay	50-1000 nM	0.5 h		dose dependently (50–1000 nM) inhibits phosphorylation of Akt
Saos-2	Function Assay	100 nM	0.5 h		prevents osteosarcoma cell migration
MG63	Apoptosis Assay	100 nM	36 h		promotes apoptosis
U2OS	Apoptosis Assay	100 nM	36 h		promotes apoptosis
Saos-2	Apoptosis Assay	100 nM	36 h		promotes apoptosis
HT1376	Growth Inhibition Assay				IC50=1.88 ± 1.1 μM
T24	Growth Inhibition Assay				IC50=1.37 ± 0.4 μM
UM-UC-3	Growth Inhibition Assay				IC50=0.63 ±0.1 μM
DLD-1	Cell Viability Assay	0-1000 nM	24 h		inhibits the growth in a dose-dependent manner
Caco2	Cell Viability Assay	0-1000 nM	24 h		inhibits the growth in a dose-dependent manner
HT29	Cell Viability Assay	0-1000 nM	24 h		inhibits the growth in a dose-dependent manner
H116	Cell Viability Assay	0-1000 nM	24 h		inhibits the growth in a dose-dependent manner
Hct-8	Cell Viability Assay	0-1000 nM	24 h		inhibits the growth in a dose-dependent manner
Colo320	Cell Viability Assay	0-1000 nM	24 h		inhibits the growth in a dose-dependent manner
Sw948	Cell Viability Assay	0-1000 nM	24 h		inhibits the growth in a dose-dependent manner
Colo205	Cell Viability Assay	0-1000 nM	24 h		inhibits the growth in a dose-dependent manner
Colo320	Function Assay	1 μM	0-24 h		abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
HT29	Function Assay	1 μM	0-24 h		abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
Sw948	Function Assay	1 μM	0-24 h		abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
DLD-1	Function Assay	1 μM	0-24 h		abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
SW620	Growth Inhibition Assay				IC50=7.8 μM
SW480	Growth Inhibition Assay				IC50=4.6 μM
SK-CO-1	Growth Inhibition Assay				IC50=4 μM
LS-513	Growth Inhibition Assay				IC50=3.9 μM
SW1116	Growth Inhibition Assay				IC50=0.84 μM
LS-174T	Growth Inhibition Assay				IC50=0.84 μM
HCT 116	Growth Inhibition Assay				IC50=0.41 μM
HCT 15	Growth Inhibition Assay				IC50=0.3 μM
COLO 205	Growth Inhibition Assay				IC50=0.24 μM
HT-29	Growth Inhibition Assay				IC50=0.23 μM
COLO 201	Growth Inhibition Assay				IC50=0.23 μM
Caco-2	Growth Inhibition Assay				IC50=0.22 μM
SW48	Growth Inhibition Assay				IC50=0.09 μM
DND-1	Growth Inhibition Assay	0.25/0.5/1 μM		DMSO	inhibits cell growth dose dependently
TMD8	Growth Inhibition Assay	0.25/0.5/1 μM		DMSO	inhibits cell growth dose dependently
Jurkat	Growth Inhibition Assay	0.25/0.5/1 μM		DMSO	inhibits cell growth dose dependently
KOPT-K1	Growth Inhibition Assay	0.25/0.5/1 μM		DMSO	inhibits cell growth dose dependently
TMD7	Growth Inhibition Assay	0.25/0.5/1 μM		DMSO	inhibits cell growth dose dependently
THP-1	Growth Inhibition Assay	0.25/0.5/1 μM		DMSO	inhibits cell growth dose dependently
786-O	Function Assay	0.1/0.5 μM	24 h	DMSO	increases E-cadherin mRNA levels dose dependently
786-O	Function Assay	0-0.5 μM	24 h	DMSO	results in a dose dependent increase in E-cadherin protein expression
OCI-AML3	Apoptosis Assay	2.5 μM	72 h		induces apoptosis
Jurkat	Function Assay	100/200/400 nM	18 h		inhibits mTORC1-dependent S6 S235/236 phosphorylation
p210 BCR-Abl	Function Assay	100/200/400 nM	18 h		inhibits mTORC1-dependent S6 S235/236 phosphorylation
Jurkat	Growth Inhibition Assay	400nM	24/48 h		synergize with 17-AAG to suppress cell proliferation
p210 BCR-Abl	Growth Inhibition Assay	400nM	24/48 h		synergize with 17-AAG to suppress cell proliferation
8226	Function Assay	100-1000 nM	30 min	DMSO	activates ERK
MM1.S	Function Assay	100-1000 nM	30 min	DMSO	activates ERK
8226	Function Assay	0.5 μM	30 min	DMSO	induces activation of RAF and phosphorylation of MEK
MM1.S	Function Assay	0.5 μM	30 min	DMSO	induces activation of RAF and phosphorylation of MEK
MCF-7	Function Assay	50/200/500 nM	30 min		dose-dependently (50–500 nM) suppresses phosphorylation of Akt
T47D	Function Assay	50/200/500 nM	30 min		dose-dependently (50–500 nM) suppresses phosphorylation of Akt
MDA-MB-231	Function Assay	50/200/500 nM	30 min		dose-dependently (50–500 nM) suppresses phosphorylation of Akt
Bcap-37	Function Assay	50/200/500 nM	30 min		dose-dependently (50–500 nM) suppresses phosphorylation of Akt
MCF-7	Apoptosis Assay	200 nM	36 h	DMSO	induces apoptosis
MDA-MB-231	Apoptosis Assay	200 nM	36 h	DMSO	induces apoptosis
Bcap-37	Apoptosis Assay	200 nM	36 h	DMSO	induces apoptosis
LS174T	Function Assay	10/100/1000 nM	6 h	DMSO	inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
DLD-1	Function Assay	10/100/1000 nM	6 h	DMSO	inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
SW480	Function Assay	10/100/1000 nM	6 h	DMSO	inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
SW-48	Growth Inhibition Assay				IC50=0.1 μM
HCT-15	Growth Inhibition Assay				IC50=0.3 μM
HCT 116	Growth Inhibition Assay				IC50=0.6 μM
SW620-R	Growth Inhibition Assay				IC50=1.3 μM
SK-CO-1	Growth Inhibition Assay				IC50=2.1 μM
SW620	Growth Inhibition Assay				IC50=11 μM
BaF3	Growth Inhibition Assay				GI50=1.449 μM
NIH 3T3	Function Assay	2 μM	18 h		inhibits mTORC2 phosphorylation of Akt on Ser473 and mTORC1 phosphorylation of 4E-BP1 on Thr37/46
HCT15	Function Assay	0.5/2 μM	4 h		prevents S6K1 phosphorylation of ribosomal protein S6 at Ser240/244 and mTORC2 phosphorylation of Akt at Ser473
SW620	Function Assay	0.5/2 μM	4 h		blocks all three mTOR outputs
Klicken Sie hier, um weitere experimentelle Zellliniendaten anzuzeigen

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht	308.34	Formel	C₁₆H₁₆N₆O	Lagerung (Ab Erhaltdatum)	3 Jahre-20°CPulver
CAS-Nr.	1092351-67-1	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	N/A			Smiles	CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(N3)C=CC(=C4)O)N

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 61 mg/mL (197.83 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 62 mg/mL (201.07 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 18 mg/mL

Water : Insoluble

DMSO : 62 mg/mL (201.07 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 18 mg/mL

Water : Insoluble

DMSO : 62 mg/mL (201.07 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 62 mg/mL (201.07 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewicht-Rechner

In vivo Charge:
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.
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 Von Selleck-Laboren validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, wenden Sie sich für kundenspezifische Tests an unser Vertriebsteam.	6.000mg/ml (19.46mM)	Taking the 1 mL working solution as an example, add 50 μL of 120 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; 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.

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie unten die Informationen ein (Empfohlen: Ein zusätzliches Tier einplanen, um Verluste während des Experiments auszugleichen)

Dosierung: mg/kg Durchschnittliches Gewicht der Tiere: g Dosierungsvolumen pro Tier:μL Anzahl der Tiere:

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

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

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

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzuμL PEG300, mischen und aufklären, fügen Sie als Nächstes hinzuμL Tween 80, mischen und aufklären, fügen Sie als Nächstes hinzu μL ddH₂O, mischen und aufklären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzu μL Maisöl, mischen und aufklären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, die Lösungsmittel in der richtigen Reihenfolge hinzuzufügen. Sie müssen sicherstellen, dass die im vorherigen Schritt erhaltene Lösung klar ist, bevor Sie das nächste Lösungsmittel hinzufügen. Physikalische Methoden wie Vortexen, Ultraschall oder ein warmes Wasserbad können zur Unterstützung des Lösungsvorgangs verwendet werden.

Wirkungsmechanismus (Mechanism of Action)

Eigenschaften	One of the first selective inhibitors that targets ATP domain of mTOR.
Targets/IC₅₀/Ki	mTOR (Cell-free assay) 8 nM p110δ (Cell-free assay) 0.10 μM DNA-PK (Cell-free assay) 0.41 μM PDGFR (Cell-free assay) 0.41 μM
In vitro	PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. This compound displays some inhibitory activity against Ret, PKCα, PKCβ, and JAK2, while exhibits remarkable selectivity against 215 other protein kinases. Unlike rapamycin, this inhibitor inhibits both mTORC1 and mTORC2. In BT549 cells, this chemical treatment (0.04-10 μM) inhibits the phosphorylation of Akt, the mTOR substrate p70S6K, and its downstream target S6 in a dose-dependent manner. It potently inhibits PKCα with IC50 of 49 nM. Low concentrations of this compound inhibit the phosphorylation of Akt S473 and higher concentrations partially inhibit Akt T308-P in addition to S473-P. As this agent is a more effective mTORC1 inhibitor than rapamycin, it inhibits the proliferation of primary MEFs, and the phosphorylation of 4EBP1 at T36/45 and S65, more potently than rapamycin. This compound but not rapamycin potently inhibits cap-dependent translation, by causing a higher level of binding between 4EBP1 and eIF4E than rapamycin. It potently inhibits the proliferation of p190-transformed murine BM, SUP-B15, and K562 cells with GI50 of 12 nM, 90 nM, and 85 nM, respectively. This inhibitor also inhibits the growth of solid tumor cell lines such as SKOV3, PC3, 786-O, and U87 with GI50 of 0.49 μM, 0.19 μM, 2.13 μM, and 1.57 μM, respectively. It is also more effective than rapamycin in achieving cytoreduction and apoptosis in multiple myeloma (MM) cells.
Kinase-Assay	In vitro mTOR (FRAP1) Kinase-Assay
Kinase-Assay	Rekombinantes mTOR wird mit dieser Verbindung in 2-fachen Verdünnungen über einen Konzentrationsbereich von 50-0,001 μM in einem Assay inkubiert, der 50 mM HEPES, pH 7,5, 1 mM EGTA, 10 mM MgCl₂, 0,01% Tween, 10 μM ATP (2,5 μCi γ-³²P-ATP) und 3 μg/mL BSA enthält. Rekombinantes Ratten-PHAS-1/4EBP1 (2 mg/mL) wird als Substrat verwendet. Die Reaktionen werden durch Auftropfen auf Nitrozellulose beendet, die mit 1 M NaCl/1% Phosphorsäure gewaschen wird (etwa 6 Mal, jeweils 5-10 Minuten). Die Blätter werden getrocknet und die übertragene Radioaktivität durch Phosphorimaging quantifiziert. Der IC50-Wert wird durch Anpassung der Daten an eine sigmoide Dosis-Wirkungs-Kurve mit dem Prism-Softwarepaket berechnet.
In vivo	Administration of PP242 is able to completely inhibit the phosphorylation of Akt at S473 and T308 in fat and liver of mice. This compound only partially inhibits the phosphorylation of Akt in skeletal muscle and is more effective at inhibiting the phosphorylation of T308 than S473, despite able to fully inhibit the phosphorylation of 4EBP1 and S6. Oral administration of this chemical potently delays the leukemia onset in the mice model, and induces leukemia regression by inhibiting mTORC2 and mTORC1 activation that correlates with loss in cell size. This treatment potently inhibits the growth of 8226 cells in mice.
Referenzen	[1] https://pubmed.ncbi.nlm.nih.gov/18849971/ [2] https://pubmed.ncbi.nlm.nih.gov/19209957/ [3] https://pubmed.ncbi.nlm.nih.gov/20072130/ [4] https://pubmed.ncbi.nlm.nih.gov/20686120/

Anwendungen (Applications)

Methoden	Biomarker	Bilder	PMID
Western blot	p-mTOR / mTOR / p-AKT / AKT / p-S6 / S6 / p-4E-BP1 / 4E-BP-1		23991179
Growth inhibition assay	Cell viability		23991179

Häufig gestellte Fragen (FAQ) (Frequently Asked Questions)

Frage 1:
Do you have any suggestions about potential candidates for vehicles that we could use for in vivo studies of it?

Antwort:
In the recommended solvent (30% PEG400 + 0.5% Tween80 + 5% Propylene glycol), it is a suspension, and this formulation is for oral gavage. For IV injection, this compound can be dissolved in 2% DMSO+30% PEG 300+5% Tween 80+ddH2O at 5mg/ml as a clear solution.

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):

Torkinib (PP242) mTOR Inhibitor

Molekulargewicht: 308.34

Qualitätskontrolle (Quality Control)

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

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Löslichkeit (Solubility)

Molaritätsrechner

In-vivo-Formulierungsrechner (Klare Lösung)

Wirkungsmechanismus (Mechanism of Action)

Anwendungen (Applications)

Häufig gestellte Fragen (FAQ) (Frequently Asked Questions)

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