Sapanisertib (INK 128, MLN0128,TAK-228)

Catalog No.S2811

Molecular Weight(MW): 309.33

Sapanisertib (INK 128, MLN0128) is a potent and selective mTOR inhibitor with IC50 of 1 nM in cell-free assays; >200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes (vs Rapamycin). Phase 1.

5 Customer Reviews

Blockade of PD-1 in combination with INK128 inhibits liver cancer cell proliferation and clone formation in vitro in immunocompetent mice. (A) Representative pictures show the clone formation of different administered groups in SMMC7721 PD-1 OE cells. (B) Histogram showing mean number of cloned formed 6 SD in each group. P < 0.05. (C) Optical density values 6 SD of Cell Counting Kit 8 assay in different administered groups in SMMC7721 PD-1 OE cells. (D,E) Flow-cytometric assessment of cell death with percent of annexin V1/7-aminoactinomycin D1 cells, mean 6 SEM. (F,G) Tumor growth kinetics (mean±SD) of different administered groups versus corresponding control in C57BL/6 mice subcutaneously implanted with PD-1 OE or vector-control Hepa1-6 cells. *P < 0.5; **P < 0.01; ***P < 0.001; #, not significant. Abbreviations: 7-AAD, 7-aminoactinomycin D; CCK8, Cell Counting Kit 8; NS, not significant; OD, optical density.

Hepatology, 2017, 66(6):1920-1933. Sapanisertib (INK 128, MLN0128,TAK-228) purchased from Selleck.

Hep-2 (D) or SCC-9 (E) cells were treated with PI3K/Akt and mTOR dual inhibitor LY 294002 (LY, 1 umol/L), mTORC1 inhibitor rapamycin (0.5 umol/L), mTORC1/2 dual inhibitor AZD2014 (0.1 uM), INK-128 (0.1 uM) or AZD8055 (0.1 uM) for 72 h, cell viability was analyzed. The mean of three independent experiments performed in triplicate was shown. Statistical significance was analyzed by ANOVA. *p < 0.01 vs Control. **p < 0.01 vs. AZD8055 group.

Biochem Biophys Res Commun 2013 440(4), 701-6. Sapanisertib (INK 128, MLN0128,TAK-228) purchased from Selleck.
(A–C), BMDMs were pretreated with or without INK128 (10, 20, or 30 nM) for 1 h and primed with LPS for 3 h. The cells were then stimulated with or without ATP. (A) Western blot analysis of IL-1β and cleaved caspase-1 in the supernatants and western blot analysis of NLRP3, pro-caspase-1 and pro-IL-1β in the lysates.

Acta Biochim Biophys Sin (Shanghai), 2018, doi: 10.1093/abbs/gmy088. Sapanisertib (INK 128, MLN0128,TAK-228) purchased from Selleck.

Antonino Maria Spart from University of Bologn. Sapanisertib (INK 128, MLN0128,TAK-228) purchased from Selleck.
Bone marrow derived macrophages were pre-treated with 1nM INK128 for 1h prior to LPS treatment (100 ng/ml). TNF-a production was analyzed 24h later.

Sapanisertib (INK 128, MLN0128,TAK-228) purchased from Selleck.

Purity & Quality Control

Choose Selective mTOR Inhibitors

Biological Activity

Description

Targets

mTOR ^[3] (Cell-free assay)	mTOR ^[3] (Cell-free assay)	PI3Kα ^[3] (Cell-free assay)	PI3Kγ ^[3] (Cell-free assay)	PI3Kδ ^[3] (Cell-free assay)	View More
1.4 nM(Ki)	1.4 nM(Ki)	219 nM	221 nM	230 nM	View More

In vitro

INK 128 exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases. ^[1] As TORC1/2 inhibitor, INK 128 inhibits both the phosphorylation of S6 and 4EBP1, the downstream substrates of TORC1, and selectively inhibits AKT phosphorylation at Ser473, the downstream substrate of TORC2. Furthermore, INK 128 also shows potent inhibition effects on cell lines resistant to rapamycin and pan-PI3K inhibitors. ^[2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
PANC-1	NYLQcFdlS2WubDDWbYFjcWyrdImgRZN{[Xl?	MY[xMVExOCCwTR?=	NWnibHhwPzJiaB?=	NGLKVoVqdmirYnn0d{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7	NWTmeFlTOjR7N{G1OFQ>
PANC-1	M3rLfWNmdGxiVnnhZoltcXS7IFHzd4F6	NYDyO2x2PTBibl2=	M17uU\|I1NTl4IHi=	MWjpcohq[mm2czDj[YxtKH[rYXLpcIl1gSC2aX3lJIRmeGWwZHXueIx6	MYSyOFk4OTV2NB?=
MIA PaCa-2	MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=>	NVXkcYV6OS1zMECgcm0>	NGCzR5U4OiCq	NETZNWxqdmirYnn0d{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7	MYiyOFk4OTV2NB?=
PANC-1	NGn3WmNCeG:ydH;zbZMhSXO\|YYm=	MX2xNE0yODBibl2=	NFPzZ2o4OiCq	NWm1NIpEcW6mdXPld{BieG:ydH;zbZMh\G:\|ZTDk[ZBmdmSnboTsfS=>	M3vW[FI1QTdzNUS0
PANC-1	NXHzNHdoTnWwY4Tpc44hSXO\|YYm=	Ml7kNVAwPTBibl2=	MknlNlQhcA>?	M3f1boRz[W2jdHnjZYxtgSCrbnjpZol1eyCyaH;zdIhwenmuYYTpc44hd2ZiNFWtRnAyNVN4S{GgLI1VV1KFMTDhZ5RqfmG2aX;uJIlv\GmlYYTvdpMqKGGwZDDBb5Qh[XRiU3XyJFQ4OyBqdHjlJI1VV1KFMjDhZ5RqfmG2aX;uJIlv\GmlYYTvdkk>	M1HuNVI1QTdzNUS0
PANC-1	NHy5UopHfW6ldHnvckBCe3OjeR?=	MVW1NEBvVQ>?	M12wd\|Q5KGh?	M3HUOYRqe3K3cITzJINmdGxiY4njcIUheHKxZ4Lld5Nqd25?	M1;DN\|I1QTdzNUS0
PANC-1	M4[yO2Z2dmO2aX;uJGF{e2G7	NXHyTHU2OTBibl2=	MWi3NkBp	MXTpcoNz\WG\|ZYOg[4Vu[2m2YXLpcoUhe2Wwc3n0bZZqfHl?	NHHrPW0zPDl5MUW0OC=>

... Click to View More Cell Line Experimental Data

In vivo

In a ZR-75-1 breast cancer xenograft model, INK 128 shows tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day. ^[1] Daily, oral administration of INK 128 inhibits angiogenesis and tumor growth in multiplexenograft models. ^[2]

Protocol

References

Solubility (25°C)

In vitro	DMSO	62 mg/mL (200.43 mM)
	Ethanol	2 mg/mL (6.46 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing.	30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Sapanisertib (INK 128, MLN0128,TAK-228) SDF

Molecular Weight	309.33
Formula	C₁₅H₁₅N₇O
CAS No.	1224844-38-5
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A

Bio Calculators

Molarity Calculator

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

Serial Dilutions
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Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
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C6=C5/X	C6:	LOG(C6):
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C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2018-11-16)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02575339	Active not recruiting	Hepatocellular Carcinoma\|Liver Cancer\|HCC	Bert O''Neil MD\|Millennium Pharmaceuticals Inc.\|Big Ten Cancer Research Consortium	July 2016	Phase 1\|Phase 2
NCT02756364	Active not recruiting	Breast Neoplasms	Millennium Pharmaceuticals Inc.\|Takeda	June 1 2016	Phase 2
NCT02724020	Active not recruiting	Clear-cell Metastatic Renal Cell Carcinoma	Millennium Pharmaceuticals Inc.\|Takeda	June 30 2016	Phase 2
NCT02719691	Recruiting	Metastatic Breast Cancer\|Solid Tumors	University of Colorado Denver	May 13 2016	Phase 1
NCT02725268	Recruiting	Endometrial Neoplasms	Millennium Pharmaceuticals Inc.\|European Network of Translational Research in Ovarian Cancer - EUTROC\|European Network of Individualized Treatment in Endometrial Cancer - ENITEC\|Takeda	April 1 2016	Phase 2
NCT02514824	Active not recruiting	Merkel Cell Carcinoma	Dana-Farber Cancer Institute\|Millennium Pharmaceuticals Inc.	October 2015	Phase 1\|Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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

If you have any other enquiries, please leave a message.

Frequently Asked Questions

Question 1:
What is the recommendation method to formulate S2811 INK 128 (MLN0128) for oral administration?
Answer:
You can try this vehicle for oral administration: 30% PEG400+0.5% Tween80 +5% Propylene glycol.

mTOR Signaling Pathway Map

mTOR Inhibitors with Unique Features

Selective mTOR inhibitor

Rapamycin (Sirolimus) : mTORC1-selective, IC50=~0.1 nM.
Most Potent mTOR Inhibitor

Rapamycin (Sirolimus) : mTOR, IC50=~0.1 nM.
FDA-approved mTOR Inhibitor

Temsirolimus (CCI-779, NSC 683864) : Approved by FDA for Renal Cell Carcinoma (RCC).
Newest mTOR Inhibitor

XL388 ^New : Highly potent, selective, ATP-competitive inhibitor of mTOR with IC50 of 9.9 nM, 1000-fold selectivity over the closely related PI3K kinases.

Related mTOR Products4

MHY1485 ^New

MHY1485 is a potent, and cell-permeable mTOR activator, and also potently inhibits autophagy.
CHIR-99021 (CT99021) ^New

CHIR-99021 (CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 of 10 nM and 6.7 nM, respectively. CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs.
Dorsomorphin (Compound C) ^New

Dorsomorphin is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type I BMP receptor activity.
Rapamycin (Sirolimus)

Rapamycin (Sirolimus) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.
Everolimus (RAD001)

Everolimus (RAD001) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM in a cell-free assay.
AZD8055

AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. Phase 1.

Features:First drug to inhibit both types of mTOR protein.
Torin 1

Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM in cell-free assays; exhibits 1000-fold selectivity for mTOR than PI3K.
Temsirolimus (CCI-779, NSC 683864)

Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay.
Tacrolimus (FK506)

Tacrolimus (FK506) is a 23-membered macrolide lactone, it reduces peptidyl-prolyl isomerase activity in T cells by binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex.
KU-0063794

KU-0063794 is a potent and highly specific dual-mTOR inhibitor of mTORC1 and mTORC2 with IC50 of ~10 nM in cell-free assays; no effect on PI3Ks.

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Sapanisertib (INK 128, MLN0128,TAK-228)