LY2584702 tosylate salt
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MedKoo CAT#: 205522

CAS#: 1082949-68-5 (tosylate)

Description: LY-2584702, also known as LYS6K2, is an orally available inhibitor of p70S6K signaling, with potential antineoplastic activity. LY2584702 inhibits ribosomal protein S6 Kinase (p70S6K), and prevents phosphorylation of the S6 subunit of ribosomes, thereby inhibiting normal ribosomal function within tumor cells leading to a decrease in protein synthesis and in cellular proliferation. P70S6K, a serine/threonine kinase, acts downstream of PIP3 and phosphoinositide-dependent kinase-1 in the PI3 kinase pathway, is often upregulated in a variety of cancer cells, and is involved in the regulation of cell growth, proliferation, motility, and survival.


Chemical Structure

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LY2584702 tosylate salt
CAS# 1082949-68-5 (tosylate)

Theoretical Analysis

MedKoo Cat#: 205522
Name: LY2584702 tosylate salt
CAS#: 1082949-68-5 (tosylate)
Chemical Formula: C28H27F4N7O3S
Exact Mass: 445.1638
Molecular Weight: 617.6236
Elemental Analysis: C, 54.45; H, 4.41; F, 12.30; N, 15.88; O, 7.77; S, 5.19

Price and Availability

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10.0mg USD 150.0 Same day
25.0mg USD 250.0 Same day
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100.0mg USD 650.0 Same day
200.0mg USD 850.0 Same day
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1.0g USD 2650.0 Same day
2.0g USD 3850.0 Same day
5.0g USD 4750.0 2 Weeks
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Related CAS #: 1082949-68-5 (tosylate)   1082949-67-4 (free base)    

Synonym: LY2584702; LY 2584702; LY-2584702; LYS6K2; LYS-6K2; LYS 6K2; LY2584702 tosylate salt.

IUPAC/Chemical Name: 4-(4-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazol-2-yl)piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine 4-methylbenzenesulfonate

InChi Key: HDYUXDNMHBQKAU-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H19F4N7.C7H8O3S/c1-31-10-17(13-2-3-16(22)15(8-13)21(23,24)25)29-19(31)12-4-6-32(7-5-12)20-14-9-28-30-18(14)26-11-27-20;1-6-2-4-7(5-3-6)11(8,9)10/h2-3,8-12H,4-7H2,1H3,(H,26,27,28,30);2-5H,1H3,(H,8,9,10)

SMILES Code: CN1C=C(C2=CC=C(F)C(C(F)(F)F)=C2)N=C1C3CCN(C4=C5C(NN=C5)=NC=N4)CC3.OS(=O)(C6=CC=C(C)C=C6)=O

Appearance: White to off-white 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

Biological target: LY-2584702 tosylate salt is a selective ATP competitive inhibitor of p70S6K with an IC50 of 4 nM. In S6K1 enzyme assay, the IC50 of LY-2584702 is 2 nM.
In vitro activity: Proliferation of A549 was significantly inhibited by LY2584702 treating over 24 h at 0.1 μM (Fig 5A, P < 0.05); and the trend of decline was more conspicuous with longer treatment and/or with the increased drug concentration (Fig 5A, all P < 0.05). Similar results were also observed in SK-MES-1, although the obvious inhibition was led by LY2584702 at 0.6 μM (Fig 5B, all P < 0.05), much higher than that of A549. Based on the results above, A549 treated by LY2584702 at 0.2 μM for 72 h were collected for cell cycle assay and apoptosis analysis. A549 cell lines cultured only by medium or medium added with DMSO for 72 h were used as controls. Not surprisingly, more cells with LY2584702 treatment were arrested in G0-G1 phase (Fig 6A, both P < 0.05); and cells in S or G2-M phase decreased correspondingly (Fig 6A, both P < 0.05). In addition, LY2584702 induced more apoptotic A549 cell by Annexin V-APC/7-AAD apoptosis detection (Fig 7A, both P < 0.05). Because of the less sensitivtiy of SK-MES-1 for LY2584702, SK-MES-1 treated at 1 μM for 72 h were employed for the cell cycle and apoptosis analysis. Silimarly, compared with controls, LY2584702 treatment also led to SK-MES-1 G0-G1 arrest and synchronous reduction in S and G2-M phase (Fig 6B, all P < 0.05). Reference: PLoS One. 2017; 12(8): e0182891. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549961/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 12.55 20.31

Preparing Stock Solutions

The following data is based on the product molecular weight 617.6236 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.

Recalculate based on batch purity %
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. Chen B, Yang L, Zhang R, Gan Y, Zhang W, Liu D, Chen H, Tang H. Hyperphosphorylation of RPS6KB1, rather than overexpression, predicts worse prognosis in non-small cell lung cancer patients. PLoS One. 2017 Aug 9;12(8):e0182891. doi: 10.1371/journal.pone.0182891. PMID: 28792981; PMCID: PMC5549961.
In vitro protocol: 1. Chen B, Yang L, Zhang R, Gan Y, Zhang W, Liu D, Chen H, Tang H. Hyperphosphorylation of RPS6KB1, rather than overexpression, predicts worse prognosis in non-small cell lung cancer patients. PLoS One. 2017 Aug 9;12(8):e0182891. doi: 10.1371/journal.pone.0182891. PMID: 28792981; PMCID: PMC5549961.
In vivo protocol: TBD

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1: Leohr JK, Luffer-Atlas D, Luo MJ, DeBrota DJ, Green C, Mabry TE, Suico JG. Serum Lipid and Protein Changes in Healthy Dyslipidemic Subjects Given a Selective Inhibitor of p70 S6 Kinase-1. J Clin Pharmacol. 2018 Apr;58(4):412-424. doi: 10.1002/jcph.1032. Epub 2017 Nov 26. PubMed PMID: 29178617.

2: Gu X, Fu X, Lu J, Saijilafu, Li B, Luo ZP, Chen J. Pharmacological inhibition of S6K1 impairs self-renewal and osteogenic differentiation of bone marrow stromal cells. J Cell Biochem. 2018 Jan;119(1):1041-1049. doi: 10.1002/jcb.26272. Epub 2017 Aug 28. PubMed PMID: 28853173.

3: Chen B, Yang L, Zhang R, Gan Y, Zhang W, Liu D, Chen H, Tang H. Hyperphosphorylation of RPS6KB1, rather than overexpression, predicts worse prognosis in non-small cell lung cancer patients. PLoS One. 2017 Aug 9;12(8):e0182891. doi: 10.1371/journal.pone.0182891. eCollection 2017. PubMed PMID: 28792981; PubMed Central PMCID: PMC5549961.

4: Estridge TB, Dey AB, Reidy C, Yu X, Zhang Y, Hartley M, Milligan PL, Jin N, Kowala MC, Leohr JK, Fretland AJ, Mabry TE, Luffer-Atlas D, Luo MJ. Identification of 4-Aminopyrazolopyrimidine Metabolite That May Contribute to the Hypolipidemic Effects of LY2584702 in Long Evans Diet-Induced Obese Rats. J Pharmacol Exp Ther. 2017 Jul;362(1):108-118. doi: 10.1124/jpet.117.240242. Epub 2017 May 2. PubMed PMID: 28465372.

5: Archambault AS, Turcotte C, Martin C, Lefebvre JS, Provost V, Laviolette M, Flamand N. Leukotriene B₄ Metabolism and p70S6 Kinase 1 Inhibitors: PF-4708671 but Not LY2584702 Inhibits CYP4F3A and the ω-Oxidation of Leukotriene B₄ In Vitro and In Cellulo. PLoS One. 2017 Jan 9;12(1):e0169804. doi: 10.1371/journal.pone.0169804. eCollection 2017. PubMed PMID: 28068410; PubMed Central PMCID: PMC5222342.

6: Hollebecque A, Houédé N, Cohen EE, Massard C, Italiano A, Westwood P, Bumgardner W, Miller J, Brail LH, Benhadji KA, Soria JC. A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with erlotinib or everolimus in patients with solid tumours. Eur J Cancer. 2014 Mar;50(5):876-84. doi: 10.1016/j.ejca.2013.12.006. Epub 2014 Jan 20. PubMed PMID: 24456794.

7: Tolcher A, Goldman J, Patnaik A, Papadopoulos KP, Westwood P, Kelly CS, Bumgardner W, Sams L, Geeganage S, Wang T, Capen AR, Huang J, Joseph S, Miller J, Benhadji KA, Brail LH, Rosen LS. A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours. Eur J Cancer. 2014 Mar;50(5):867-75. doi: 10.1016/j.ejca.2013.11.039. Epub 2014 Jan 15. PubMed PMID: 24440085.



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