KU-0063794 | CAS#938440-64-3 | mTOR inhibitor

KU-0063794
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205776

CAS#: 938440-64-3

Description: KU-0063794 is a potent and selective mTOT inhibitor, which inhibits both mTORC1 and mTORC2 with an IC50 of approximately 10 nM, but does not suppress the activity of 76 other protein kinases or seven lipid kinases, including Class 1 PI3Ks (phosphoinositide 3-kinases) at 1000-fold higher concentrations. KU-0063794 is cell permeant, suppresses activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK (ribosomal S6 kinase), an AGC kinase not regulated by mTOR. Ku-0063794 also inhibited phosphorylation of the T-loop Thr308 residue of Akt phosphorylated by PDK1 (3-phosphoinositide-dependent protein kinase-1). Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated.(Source: Biochem J. 2009 Jun 12;421(1):29-42)

Chemical Structure

KU-0063794

CAS# 938440-64-3

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205776
Name: KU-0063794
CAS#: 938440-64-3
Chemical Formula: C25H31N5O4
Exact Mass: 465.24
Molecular Weight: 465.545
Elemental Analysis: C, 64.50; H, 6.71; N, 15.04; O, 13.75

Price and Availability

Size	Price	Availability	Quantity
25mg	USD 150
50mg	USD 250
100mg	USD 450
200mg	USD 850
500mg	USD 1650
1g	USD 2950
2g	USD 4850
5g	USD 7650
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: KU0063794; KU-0063794; KU 0063794; Ku0063794; Ku 0063794; Ku-0063794; KU63794; KU 63794; KU-63794.

IUPAC/Chemical Name: (5-(2-((2R,6S)-2,6-dimethylmorpholino)-4-morpholinopyrido[2,3-d]pyrimidin-7-yl)-2-methoxyphenyl)methanol

InChi Key: RFSMUFRPPYDYRD-CALCHBBNSA-N

InChi Code: InChI=1S/C25H31N5O4/c1-16-13-30(14-17(2)34-16)25-27-23-20(24(28-25)29-8-10-33-11-9-29)5-6-21(26-23)18-4-7-22(32-3)19(12-18)15-31/h4-7,12,16-17,31H,8-11,13-15H2,1-3H3/t16-,17+

SMILES Code: OCC1=CC(C2=NC3=NC(N4C[C@@H](C)O[C@@H](C)C4)=NC(N5CCOCC5)=C3C=C2)=CC=C1OC

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

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Product Data:

Product Data

Instruction:

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Biological target:	KU-0063794 is a potent and specific mTOR inhibitor, inhibiting both the mTORC1 and mTORC2 complexes with IC50s of 10 nM.
In vitro activity:	The ATP-competitive mTOR inhibitor ku-0063794 showed dramatic antiproliferative effects and G1-cell cycle arrest in both sensitive and resistant cells. Ku-0063794 at the IC50 concentration effectively inhibited both mTOR and p70S6K phosphorylation levels; the latter is an mTORC1 substrate and did not upregulate Akt ser473 phosphorylation which would be induced by rapamycin and resulted in partial inhibition of FOXO1 phosphorylation. Reference: PLoS One. 2013 Jul 16;8(7):e69104. https://pubmed.ncbi.nlm.nih.gov/23874880/
In vivo activity:	Consistent with this possibility, temsirolimus, but not Ku0063794, decreased tumor angiogenesis in vivo, and decreased the viability of HUVEC (Human Umbilical Vein Endothelial Cells) cells in vitro at pharmacologically relevant concentrations. Reference: PLoS One. 2013;8(1):e54918. https://pubmed.ncbi.nlm.nih.gov/23349989/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	5.0	10.74
	DMF:PBS (pH 7.2) (1:1)	0.5	1.07
	DMSO	9.8	21.12

Preparing Stock Solutions

The following data is based on the product molecular weight 465.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Fei SJ, Zhang XC, Dong S, Cheng H, Zhang YF, Huang L, Zhou HY, Xie Z, Chen ZH, Wu YL. Targeting mTOR to overcome epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small cell lung cancer cells. PLoS One. 2013 Jul 16;8(7):e69104. doi: 10.1371/journal.pone.0069104. PMID: 23874880; PMCID: PMC3712950. 2. Collak FK, Yagiz K, Luthringer DJ, Erkaya B, Cinar B. Threonine-120 phosphorylation regulated by phosphoinositide-3-kinase/Akt and mammalian target of rapamycin pathway signaling limits the antitumor activity of mammalian sterile 20-like kinase 1. J Biol Chem. 2012 Jul 6;287(28):23698-709. doi: 10.1074/jbc.M112.358713. Epub 2012 May 22. PMID: 22619175; PMCID: PMC3390644. 3. Zhang H, Berel D, Wang Y, Li P, Bhowmick NA, Figlin RA, Kim HL. A comparison of Ku0063794, a dual mTORC1 and mTORC2 inhibitor, and temsirolimus in preclinical renal cell carcinoma models. PLoS One. 2013;8(1):e54918. doi: 10.1371/journal.pone.0054918. Epub 2013 Jan 22. PMID: 23349989; PMCID: PMC3551765.
In vitro protocol:	1. Fei SJ, Zhang XC, Dong S, Cheng H, Zhang YF, Huang L, Zhou HY, Xie Z, Chen ZH, Wu YL. Targeting mTOR to overcome epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small cell lung cancer cells. PLoS One. 2013 Jul 16;8(7):e69104. doi: 10.1371/journal.pone.0069104. PMID: 23874880; PMCID: PMC3712950. 2. Collak FK, Yagiz K, Luthringer DJ, Erkaya B, Cinar B. Threonine-120 phosphorylation regulated by phosphoinositide-3-kinase/Akt and mammalian target of rapamycin pathway signaling limits the antitumor activity of mammalian sterile 20-like kinase 1. J Biol Chem. 2012 Jul 6;287(28):23698-709. doi: 10.1074/jbc.M112.358713. Epub 2012 May 22. PMID: 22619175; PMCID: PMC3390644.
In vivo protocol:	1. Zhang H, Berel D, Wang Y, Li P, Bhowmick NA, Figlin RA, Kim HL. A comparison of Ku0063794, a dual mTORC1 and mTORC2 inhibitor, and temsirolimus in preclinical renal cell carcinoma models. PLoS One. 2013;8(1):e54918. doi: 10.1371/journal.pone.0054918. Epub 2013 Jan 22. PMID: 23349989; PMCID: PMC3551765.

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1: Fan QW, Weiss WA. Inhibition of PI3K-Akt-mTOR signaling in glioblastoma by mTORC1/2 inhibitors. Methods Mol Biol. 2012;821:349-59. PubMed PMID: 22125077.

2: Case N, Thomas J, Sen B, Styner M, Xie Z, Galior K, Rubin J. Mechanical regulation of glycogen synthase kinase 3β (GSK3β) in mesenchymal stem cells is dependent on Akt protein serine 473 phosphorylation via mTORC2 protein. J Biol Chem. 2011 Nov 11;286(45):39450-6. Epub 2011 Sep 28. PubMed PMID: 21956113; PubMed Central PMCID: PMC3234768.

3: Dormond-Meuwly A, Roulin D, Dufour M, Benoit M, Demartines N, Dormond O. The inhibition of MAPK potentiates the anti-angiogenic efficacy of mTOR inhibitors. Biochem Biophys Res Commun. 2011 Apr 22;407(4):714-9. Epub 2011 Mar 23. PubMed PMID: 21439267.

4: Cheng J, Wang Y, Ma Y, Chan BT, Yang M, Liang A, Zhang L, Li H, Du J. The mechanical stress-activated serum-, glucocorticoid-regulated kinase 1 contributes to neointima formation in vein grafts. Circ Res. 2010 Nov 12;107(10):1265-74. Epub 2010 Sep 30. Erratum in: Circ Res. 2011 Jan 7;108(1):e1. PubMed PMID: 20884880.

5: Sturgill TW, Hall MN. Activating mutations in TOR are in similar structures as oncogenic mutations in PI3KCalpha. ACS Chem Biol. 2009 Dec 18;4(12):999-1015. PubMed PMID: 19902965; PubMed Central PMCID: PMC2796128.

6: Malagu K, Duggan H, Menear K, Hummersone M, Gomez S, Bailey C, Edwards P, Drzewiecki J, Leroux F, Quesada MJ, Hermann G, Maine S, Molyneaux CA, Le Gall A, Pullen J, Hickson I, Smith L, Maguire S, Martin N, Smith G, Pass M. The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5950-3. Epub 2009 Aug 13. PubMed PMID: 19762236.

7: GarcÃa-MartÃnez JM, Moran J, Clarke RG, Gray A, Cosulich SC, Chresta CM, Alessi DR. Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR). Biochem J. 2009 Jun 12;421(1):29-42. PubMed PMID: 19402821; PubMed Central PMCID: PMC2708931.

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