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Torkinib (PP242) mTOR inhibitor

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

Cat.nr.: S2218

Torkinib (PP242) is a selective mTOR inhibitor with IC50 of 8 nM in cell-free assays; this compound targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. It induces mitophagy and apoptosis.

Torkinib (PP242) mTOR inhibitor Chemical Structure

Chemische structuur

Molecuulgewicht: 308.34

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.50%

99.50

Gerelateerde doelwitten	PI3K Akt GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Overig mTOR Inhibitoren	Torin 1 Torin 2 AZD8055 Ridaforolimus (Deforolimus, MK-8669) Sapanisertib (MLN0128, INK-128) MHY1485 Vistusertib (AZD2014) KU-0063794 OSI-027 3BDO

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving
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
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	308.34	Formule	C₁₆H₁₆N₆O	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	1092351-67-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(N3)C=CC(=C4)O)N

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 61 mg/mL (197.83 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	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 formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Kenmerken	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	Recombinant mTOR wordt geïncubeerd met deze verbinding in 2-voudige verdunningen over een concentratiebereik van 50-0,001 μM in een assay die 50 mM HEPES, pH 7,5, 1 mM EGTA, 10 mM MgCl₂, 0,01% Tween, 10 μM ATP (2,5 μCi γ-³²P-ATP) en 3 μg/mL BSA bevat. Rat recombinant PHAS-1/4EBP1 (2 mg/mL) wordt gebruikt als substraat. Reacties worden beëindigd door op nitrocellulose te spotten, die wordt gewassen met 1 M NaCl/1% fosforzuur (ongeveer 6 keer, elk 5-10 minuten). De vellen worden gedroogd en de overgedragen radioactiviteit gekwantificeerd door fosforbeeldvorming. De IC50-waarde wordt berekend door de gegevens te fitten aan een sigmoïdale dosis-respons curve met behulp van het Prism-softwarepakket.
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.
Referenties	[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/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	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

Veelgestelde vragen (Frequently Asked Questions)

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

Antwoord:
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):
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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):