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INK 128 (MLN0128)

INK 128 (MLN0128)

Catalog No.

A8551

MTOR(TORC-1/-2) inhibitor,potent and selective

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Grouped product items
Size	Price	Stock
10mM (in 1mL DMSO)	$94.00	In stock
5mg	$88.00	In stock
10mg	$110.00	In stock
50mg	$275.00	In stock

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Background
Product Citation
Chemical Properties
Protocol
Biological Activity
Quality Control

Background

INK 128 (MLN0128) is a selective inhibitor of mTOR with IC50 value of 1 nM [3].

mTOR (mammalian target of rapamycin) is an evolutionarily conserved serine/threonine kinase which combined PI3K/AKT/mTOR pathway and plays an important role in regulating many fundamental features of cell growth and division [1].

INK 128 (MLN0128) is a potent mTOR inhibitor. When tested with human pancreatic cancer cells, INK-128 treatment inhibited cell growth and survival via inhibiting mTOR in a time- and concentration- dependent manner [2]. In HER2-positive breast cell lines, INK 128 treatment significantly delayed cell cycle and inhibited cell proliferation through inhibiting mTOR [1].

In a ZR-75-1 breast cancer xenograft model, INK128 treatment in a dose of 0.3mg/Kg/day significantly inhibited tumor growth. When combined with other standard targeted therapy or chemotherapy such as sorafenib, sutent and paclitaxel, enhanced anti-tumor growth activity was observed. INK128 is reported to have excellent physiochemical properties and is currently undergoing preclinical evaluation [3]. When tested with MDA-MB361 mouse model, administration of INK 128 showed a resistance after 20 days, and combined with lapatinib resulted in long-lasting tumor regression [1].

References:
[1].? Garcia-Garcia, C., et al., Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy. Clin Cancer Res, 2012. 18(9): p. 2603-12.
[2].? Lou, H.Z., et al., The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells. Biochem Biophys Res Commun, 2014. 450(2): p. 973-8.
[3].? Jessen K, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral anti-tumor activity. AACR 2009 Molecular targets and cancer therapeutics meeting poster; Boston: 2009.

Product Citation

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Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	309.33
Cas No.	1224844-38-5
Formula	C₁₅H₁₅N₇O
Synonyms	INK128; INK-128
Solubility	insoluble in H2O; ≥15.45 mg/mL in DMSO; ≥2.7 mg/mL in EtOH with gentle warming
Chemical Name	5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine
SDF	Download SDF
Canonical SMILES	CC(C)N1C2=C(C(=N1)C3=CC4=C(C=C3)OC(=N4)N)C(=NC=N2)N
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Kinase experiment [1]:
Kinase assays	mTOR activity was assayed using LanthaScreen Kinase kit reagents. PI(3)K α, β, γ and δ activity were assayed using the PI(3)KHTRF assay kit. The concentration of INK 128 necessary to achieve inhibition of enzyme activity by 50% (IC50) was calculated using concentrations ranging from 20 μM to 0.1 nM (12-point curve). IC50 values were determined using a nonlinear regression model.
Cell experiment [2]:
Cell lines	PANC-1 cells
Preparation method	The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
Reacting condition	10 ~ 100 nM; 72 hrs
Applications	INK 128 time- and dose-dependently inhibited the survival of PANC-1 cells, and significantly reduced the viability of PANC-1 cells at the concentrations of 10 ~ 100 nM. There was no significant viability decrease until 48 hrs after INK 128 treatment.
Animal experiment [3]:
Animal models	A ZR-75-1 breast cancer xenograft model
Dosage form	0.3 mg/kg/day; p.o.
Applications	In a ZR-75-1 breast cancer xenograft model, INK 128 significantly inhibited tumor growth. The combination therapy of INK 128 and other standard targeted therapy or chemotherapy such as Sorafenib, Sutent and Paclitaxel enhanced anti-tumor growth activity.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ, Wang S, Ren P, Martin M, Jessen K, Feldman ME, Weissman JS, Shokat KM, Rommel C, Ruggero D. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012 Feb 22;485(7396):55-61. [2]. Lou, H.Z., et al., The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells. Biochem Biophys Res Commun, 2014. 450(2): p. 973-8. [3]. Jessen K, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral anti-tumor activity. AACR 2009 Molecular targets and cancer therapeutics meeting poster; Boston: 2009.

Biological Activity

Description	INK 128 (MLN0128) is a potent and selective inhibitor of mTOR with an IC50 value of 1 nM.
Targets	mTOR	PI3Kα	PI3Kγ	PI3Kδ	PI3Kβ
IC50	1 nM (Ki=1.4 nM)	219 nM	221 nM	230 nM	5293 nM