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LY2584702 Tosylate (LYS-6K2)

Alias: LYS6K2 tosylate; LY2584702; LY 2584702; 1082949-68-5; LY2584702 tosylate; LY-2584702 (tosylate salt); LY-2584702 tosylate salt; LY 2584702 tosylate; 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; 4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;4-methylbenzenesulfonic acid; 4-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine p-toluenesulfonate; LY-2584702; LYS-6K2; LYS 6K2; LY2584702 tosylate
Cat No.:V0241 Purity: ≥98%
LY2584702 Tosylate (also known as LYS6K2), the tosylate salt ofLY2584702,isa selective, orally bioavailable, and ATP-competitive p70S6K (ribosomal p70 S6 kinase) inhibitor with potential antitumor activity.
LY2584702 Tosylate (LYS-6K2)
LY2584702 Tosylate (LYS-6K2) Chemical Structure CAS No.: 1082949-68-5
Product category: S6 kinase
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of LY2584702 Tosylate (LYS-6K2):

  • LY2584702
  • LY-2584702 hydrochloride
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description
LY2584702 Tosylate (also known as LYS6K2), the tosylate salt ofLY2584702,isa selective, orally bioavailable, and ATP-competitive p70S6K (ribosomal p70 S6 kinase) inhibitor with potential antitumor activity. Its IC50 for inhibiting p70S6K is 4 nM. By inhibiting the ribosomal protein S6 kinase (p70S6K) and preventing the phosphorylation of the S6 subunit of ribosomes, LY2584702 demonstrated strong antiproliferative activity in vitro and high antitumor efficacy in vivo. This inhibition of normal ribosomal function within tumor cells results in a reduction in protein synthesis and cellular proliferation.
Biological Activity I Assay Protocols (From Reference)
Targets
p70S6K (IC50 = 4 nM)
ln Vitro
LY2584702 inhibits the phosphorylation of the S6 ribosomal protein (pS6) in HCT116 colon cancer cells with an IC50 of 0.1-0.24 μM. [1] When combined with the mTOR inhibitor everolimus or the EGFR inhibitor erlotinib, LY2584702 exhibits notable synergistic effects. [2]
The inhibitor of RPS6KB1, LY2584702, significantly reduced the phosphorylation of RPS6KB1 and rpS6 in NSCLC cell lines [4]
LY2584702 was used to inhibit the phosphorylation of RPS6KB1 in pulmonary adenocarcinoma cell line A549 and squamous cell carcinoma cell line SK-MES-1. As expected, after the treatment for 24 h, phosphorylation of RPS6KB1 in A549 was markedly reduced even at 0.1 μM (Fig 4, P < 0.001); while the expression of p-RPS6KB1 in SK-MES-1 seemed to start decreasing at 0.2 μM and showed a continous down-regulation with increased drug concentrations (Fig 4, all P < 0.05). The phosphorylation of rpS6, generally accepted target of RPS6KB1, was also synchronously declined (Fig 4, all P < 0.05). However, there was no significant difference in total protein level of neither RPS6KB1 nor S6, no matter with the drug concentration (Fig 4, all P > 0.05).


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). However, LY2584702 showed a limited effect on SK-MES-1 apoptosis, in spite of a vague increase trend (Fig 7B, both P > 0.05).
ln Vivo
In both the U87MG glioblastoma and the HCT116 colon carcinoma xenograft models, LY2584702 (12.5 mg/kg BID) exhibits significant antitumor efficacy.[1]
Thirty-four patients were enrolled onto this phase I study and treated with LY2584702 on a QD (once-daily) or BID (twice-daily) dosing schedule. Part A dose escalation (n=22) began with 300 mg BID (n=2). Due to toxicity, this was scaled back to doses of 25mg (n=3), 50 mg (n=8), 100mg (n=3), and 200 mg (n=6) QD. Part B dose escalation (n=12) included 50 mg (n=3), 75 mg (n=3), and 100 mg (n=6) BID. Seven patients experienced dose-limiting toxicity (DLT). All DLTs were Grade 3 and included vomiting, increased lipase, nausea, hypophosphataemia, fatigue and pancreatitis. Conclusion: The MTD was determined to be 75 mg BID or 100mg QD. No responses were observed at these levels. Pharmacokinetic analysis revealed substantial variability in exposure and determined that LY2584702 treatment was not dose proportional with increasing dose.[1]
Twenty-nine patients were enrolled, 17 in Arm A and 12 in Arm B. Dose limiting toxicities (DLTs) in cycle 1 were observed in Arm A in four patients and consisted of Grade 3 vomiting, hypophosphataemia, pulmonary embolism and decreased clotting factor V. No DLTs were observed in Arm B at cycle 1, and the most frequent treatment-emergent adverse events related to study drug were: fatigue, anorexia, diarrhoea, nausea and vomiting. Seven patients received ≥4 cycles (3 in A, 4 in B). Best overall response was stable disease. Exposure accumulation of LY2584702 occurred with BID (twice daily) dosing. Exposure of erlotinib increased when administered in combination with LY2584702. Conclusion: LY2584702 was not well tolerated when administered with erlotinib, therefore this combination is not feasible. The combination with everolimus was better tolerated but yielded very limited clinical benefit [2].
Enzyme Assay
RPS6KB1 is the kinase of ribosomal protein S6 which is 70 kDa and is required for protein translation. Although the abnormal activation of RPS6KB1 has been found in types of diseases, its role and clinical significance in non-small cell lung cancer (NSCLC) has not been fully investigated. In this study, we identified that RPS6KB1 was over-phosphorylated (p-RPS6KB1) in NSCLC and it was an independent unfavorable prognostic marker for NSCLC patients. In spite of the frequent expression of total RPS6KB1 and p-RPS6KB1 in NSCLC specimens by immunohistochemical staining (IHC), only p-RPS6KB1 was associated with the clinicopathologic characteristics of NSCLC subjects. Kaplan-Meier survival analysis revealed that the increased expression of p-RPS6KB1 indicated a poorer 5-year overall survival (OS) for NSCLC patients, while the difference between the positive or negative RPS6KB1 group was not significant. Univariate and multivariate Cox regression analysis was then used to confirm the independent prognostic value of p-RPS6KB1. To illustrate the underlying mechanism of RPS6KB1 phosphorylation in NSCLC, LY2584702 was employed to inhibit the RPS6KB1 phosphorylation specifically both in lung adenocarcinoma cell line A549 and squamous cell carcinoma cell line SK-MES-1. As expected, RPS6KB1 dephosphorylation remarkably suppressed cells proliferation in CCK-8 test, and promoted more cells arresting in G0-G1 phase by cell cycle analysis. Moreover, apoptotic A549 cells with RPS6KB1 dephosphorylation increased dramatically, with an elevating trend in SK-MES-1, indicating a potential involvement of RPS6KB1 phosphorylation in inducing apoptosis. In conclusion, our data suggest that RPS6KB1 is over-activated as p-RPS6KB1 in NSCLC, rather than just the total protein overexpressing. The phosphorylation level of RPS6KB1 might be used as a novel prognostic marker for NSCLC patients[4].
Cell Assay
LY-2584702 is completely dissolved in 20 mL of 10% DMSO and stored at -80°C. When conducting the experiments in vitro, LY-2584702 is further diluted in 0.5% Tween 80, 5% propylene glycol, and 30% PEG400 to achieve various DMSO concentrations of 0.1 μM, 0.2 μM, 0.6 μM, and 1.0 μM. In vitro cell proliferation is assessed using the Cell Counting Kit-8 (CCK-8). A549 and SK-MES-1 cell lines that have been exposed to LY-2584702 at various concentrations for 24 hours are seeded in 96-well plates at a density of 5 103 cells per well with six repetitions. The concentration of LY-2584702 at zero is used as a negative control, or DMSO treated. Every 24 hours after seeding, cells' absorbance at 450 nm is measured to gauge their proliferative activities.
Animal Protocol
Mice; LY-2584702 is prepared in 0.25% Tween-80 and 0.05% antifoam, and administered orally to mice (12.5 mg/kg twice daily). Injections of EOMA cells (0.3×106) are made subcutaneously into nu/nu female mice aged 6 to 8 weeks (2 sites/mouse, 4-5 mice/group). Every day, the tumor's size is determined. Animals are either given a vehicle control or the drug LY-2584702 (12.5 mg/kg twice daily, oral dosing) for treatment when tumors grow to a size of 0.01 cm3. Every 3–4 days, tumor size is determined.[3]
ADME/Pharmacokinetics
Pharmacokinetics [1]
PK analyses were performed for both Parts A and B and, data are summarised in Table 4. The original protocol began dosing at 300 mg BID, but the two patients taking 300 mg BID experienced severe nausea and vomiting. Analysis of LY2584702 exposure level in the plasma indicated that we had exceeded the range predicted for effective target inhibition. Additionally, metabolic clearance was 10 L/h as compared to the predicted 26 L/h. Therefore, a new QD dosing scheme was implemented and ranged from 25 to 200 mg. Upon analysis of the exposures achieved with QD dosing, a BID cohort was opened to determine if BID dosing would improve total daily exposure. In the BID cohort, the MTD was determined to be 75 mg. The MTD for QD dosing was 100 mg. The half-life was conserved among cohorts at 5.96 h, but exposure (AUC) and Cmax were variable. Exposure of LY2584702 was not dose proportional but did increase with dose. LY2584702 exposures did not accumulate with QD dosing with a median accumulation ratio [AUC(0–24) day 8/AUC(0–24) day 1] of 0.61 (range: 0.52–1.7). There was accumulation with BID dosing with a median accumulation ratio of 1.98 (range: 1.1–2.69), but there was no evidence that exposure was time-dependent with median time dependency (AUC(0–24)/AUC(0–∞)) of 0.45 (range, 0.41–1.03) for QD dosing and 1.12 (range, 0.61–1.34) for BID dosing.
Pharmacokinetics [2]
PK parameters for LY2584702 were analysed and are summarised in (Table 4). LY2584702 exposure increased dose-proportionally when concomitantly administered with erlotinib, and the dose-normalised AUC for 50 mg QD and 50 mg BID were 88.73 ng h/mL/mg and 86.16 ng h/mL/mg, respectively. The AUC increased slightly at 75 mg BID (107.89 ng h/mL/mg) but decreased at 100 mg BID (86.11 ng h/mL/mg). The LY2584702 exposure increased dose-proportionally when administered concomitantly with everolimus. The dose-normalised AUC values were 121.95, 114.00 and 114.10 ng h/mL/mg for 50 mg BID, 50 mg QD and 100 QD, respectively. For dosing with erlotinib and everolimus, the median accumulation ratio for QD dosing was 1.09 and 1.07 (range, 0.98–1.16) and 2.16 and 1.98 (range, 1.85–3.41) for BID dosing. There was a significant difference (p = 0.0145, t-test) in LY2584702 exposure between QD and BID dosing with accumulation ratios of 1.08 and 2.46, respectively. Over all the dose groups, V/F exhibited high variability 34.52 L (47% CV).
Toxicity/Toxicokinetics
Toxicity [1]
Thirty-four patients received at least one dose of LY2584702, and 13 (38%) experienced a serious adverse event (SAE) during treatment. Of the 13 patients with SAE, three were related to study drug. One patient experienced Grade 3 hypophosphataemia, a second experienced Grade 3 vomiting and Grade 3 pancreatitis and a third experienced Grade 3 pancreatitis. Three patients (9%) discontinued treatment due to AE. One patient died due to progressive disease during the 30-day follow-up period after discontinuing study drug (per physician decision). This patient received one dose of study drug at 100 mg BID but was discontinued from the study due to progressive disease prior to death. Five patients in Part A and two patients in Part B experienced DLTs. All DLTs were Grade 3 and included vomiting, lipase, nausea, hypophosphataemia, fatigue and pancreatitis (Table 2). Thirty-one of 34 patients reported at least one treatment-emergent adverse event (TEAE) with 21 (62%) reporting at least one TEAE possibly related to study drug. The most common TEAEs possibly related to study drug were nausea (26%), fatigue (18%) and vomiting (15%) (Table 3). Twenty-two of 55 study drug-related AEs were ⩾Grade 3.
Toxicity [2]
Twenty-nine patients enrolled, and four had DLTs ⩾Grade 3: one case each of hypophosphataemia, vomiting, thromboembolic event and decreased levels of coagulation factor V (Table 2). In Arm A, eight patients (47%) experienced serious adverse events (SAEs), and six patients (50%) experienced SAEs in Arm B. SAE possibly related to study drug included: Grade 3 nausea, Grade 3 vomiting, Grade 3 anorexia, Grade 3 gastritis, grade 3 pulmonary embolism, Grade 3 increased international normalised ratio (INR), Grade 2 interstitial lung disease, Grade 2 deep vein thrombosis. Three patients (17.6%, n = 17) in Arm A and two patients (16.7%, n = 12) in Arm B discontinued treatment due to AEs. The most common drug related treatment-emergent adverse events (TEAE) were fatigue (88%), anorexia (71%), diarrhoea (65%), nausea (53%), rash acneiform (53%) and vomiting (41%) in Arm A; and fatigue (83%), anorexia (67%), nausea (58%), diarrhoea (50%) and oral mucositis (50%) in Arm B (Table 3). Eleven patients in Arm A (n = 17) and eight patients in Arm B (n = 12) experienced Grade 3/4 TEAE.
Three patients in Arm A and one patient in Arm B exhibited coagulation abnormalities. One patient in Arm A experienced thromboembolic event (pulmonary embolism), and one patient in Arm B experienced a possibly related SAE of deep venous thrombosis. A third patient experienced decreased coagulation Factor V, which changed from 60% (day 1) to 24% (day 8) then recovered to 85% (day 15) and again declined to 35% (day 22) all in cycle 1. There were no clinically significant changes in intrinsic coagulation pathway factors IX, XI, XII and thromboplastin (TP). A fourth patient in Arm A experienced DLT of hypophosphataemia accompanied with increased INR along with decreases in clotting factors II, V, VII and X (Fig. 1). The changes observed were induced by treatment and improved after treatment discontinuation. Several patients in both arms experienced weight loss while on treatment and ranged from 3% to 10% in Arm A and 4–11% in Arm B. Three patients (18%) in Arm A and six patients (50%) in Arm B experienced weight loss ⩾10% of baseline (Fig. 2). Dose escalation stopped in arm B after occurrence of thromboembolic events in Arm A and B and observance of other toxicities (fatigue and weight loss).
References

[1]. Eur J Cancer. 2014 Mar;50(5):867-75.

[2]. Eur J Cancer. 2014 Mar;50(5):876-84.

[3]. Cancer Res. 2015 Jan 1;75(1):40-50.

[4]. PLoS One. 2017 Aug 9;12(8):e0182891.

Additional Infomation
Background: LY2584702 tosylate (hereafter referred to as LY2584702) is a potent, highly selective adenosine triphosphate (ATP) competitive inhibitor against p70 S6 kinase, a downstream component of the phosphatidylinositol-3-kinase signalling pathway which regulates cell proliferation and survival. LY2584702 exhibited anti-tumour activity in preclinical analysis.[1]
Methods: Patients with advanced solid tumours were treated with LY2584702 orally on a 28-day cycle until the criteria for maximum tolerated dose (MTD) were met. Skin biopsies were collected for pharmacodynamic analysis, and levels of phospho-S6 protein were examined. The primary objective was to determine a phase II dose and schedule with secondary objectives of observing safety and tolerability. Dose escalation was based upon Common Terminology Criteria for Adverse Events Version 3.0.[1]
Results: Thirty-four patients were enrolled onto this phase I study and treated with LY2584702 on a QD (once-daily) or BID (twice-daily) dosing schedule. Part A dose escalation (n=22) began with 300 mg BID (n=2). Due to toxicity, this was scaled back to doses of 25mg (n=3), 50 mg (n=8), 100mg (n=3), and 200 mg (n=6) QD. Part B dose escalation (n=12) included 50 mg (n=3), 75 mg (n=3), and 100 mg (n=6) BID. Seven patients experienced dose-limiting toxicity (DLT). All DLTs were Grade 3 and included vomiting, increased lipase, nausea, hypophosphataemia, fatigue and pancreatitis.[1]
Conclusion: The MTD was determined to be 75 mg BID or 100mg QD. No responses were observed at these levels. Pharmacokinetic analysis revealed substantial variability in exposure and determined that LY2584702 treatment was not dose proportional with increasing dose. Trial registration: ClinicalTrials.gov NCT01394003.[1]
Background: LY2584702 tosylate (hereafter referred to as LY2584702) is an oral, selective ATP competitive inhibitor of p70 S6 kinase. Preclinical studies with LY2584702 demonstrated significant synergistic activity with erlotinib and everolimus. The primary objective was to determine a phase II dose and schedule. Secondary objectives included evaluation of safety, toxicity and pharmacokinetics of LY2584702 in combination with erlotinib or everolimus.[2]
Methods: Patients with advanced solid tumours were treated with a total daily dose of 50-200mg of LY2584702 in combination with erlotinib 150 mg once daily (Arm A) or everolimus 10mg once daily (Arm B). Dose escalation was based on 3+3 design and used the Common Terminology Criteria for Adverse Events Version 4.0.[2]
Results: Twenty-nine patients were enrolled, 17 in Arm A and 12 in Arm B. Dose limiting toxicities (DLTs) in cycle 1 were observed in Arm A in four patients and consisted of Grade 3 vomiting, hypophosphataemia, pulmonary embolism and decreased clotting factor V. No DLTs were observed in Arm B at cycle 1, and the most frequent treatment-emergent adverse events related to study drug were: fatigue, anorexia, diarrhoea, nausea and vomiting. Seven patients received ≥4 cycles (3 in A, 4 in B). Best overall response was stable disease. Exposure accumulation of LY2584702 occurred with BID (twice daily) dosing. Exposure of erlotinib increased when administered in combination with LY2584702.[2]
Conclusion: LY2584702 was not well tolerated when administered with erlotinib, therefore this combination is not feasible. The combination with everolimus was better tolerated but yielded very limited clinical benefit.[2]
Trial registration: ClinicalTrials.gov NCT01115803.[2]
Vascular tumors are endothelial cell neoplasms whose mechanisms of tumorigenesis are poorly understood. Moreover, current therapies, particularly those for malignant lesions, have little beneficial effect on clinical outcomes. In this study, we show that endothelial activation of the Akt1 kinase is sufficient to drive de novo tumor formation. Mechanistic investigations uncovered opposing functions for different Akt isoforms in this regulation, where Akt1 promotes and Akt3 inhibits vascular tumor growth. Akt3 exerted negative effects on tumor endothelial cell growth and migration by inhibiting activation of the translation regulatory kinase S6-Kinase (S6K) through modulation of Rictor expression. S6K in turn acted through a negative feedback loop to restrain Akt3 expression. Conversely, S6K signaling was increased in vascular tumor cells where Akt3 was silenced, and the growth of these tumor cells was inhibited by a novel S6K inhibitor. Overall, our findings offer a preclinical proof of concept for the therapeutic utility of treating vascular tumors, such as angiosarcomas, with S6K inhibitors.[3]
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C28H27F4N7O3S
Molecular Weight
617.62
Exact Mass
617.183
Elemental Analysis
C, 54.45; H, 4.41; F, 12.30; N, 15.88; O, 7.77; S, 5.19
CAS #
1082949-68-5
Related CAS #
LY-2584702 free base;1082949-67-4;LY-2584702 hydrochloride;1082948-81-9
PubChem CID
46205871
Appearance
White to off-white solid powder
LogP
6.682
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
12
Rotatable Bond Count
4
Heavy Atom Count
43
Complexity
851
Defined Atom Stereocenter Count
0
SMILES
S(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])(=O)(=O)O[H].FC1C([H])=C([H])C(=C([H])C=1C(F)(F)F)C1=C([H])N(C([H])([H])[H])C(C2([H])C([H])([H])C([H])([H])N(C3C4C([H])=NN([H])C=4N=C([H])N=3)C([H])([H])C2([H])[H])=N1
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)
Chemical Name
4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;4-methylbenzenesulfonic acid
Synonyms
LYS6K2 tosylate; LY2584702; LY 2584702; 1082949-68-5; LY2584702 tosylate; LY-2584702 (tosylate salt); LY-2584702 tosylate salt; LY 2584702 tosylate; 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; 4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;4-methylbenzenesulfonic acid; 4-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine p-toluenesulfonate; LY-2584702; LYS-6K2; LYS 6K2; LY2584702 tosylate
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~7 mg/mL (~11.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 1 mg/mL (1.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: 1 mg/mL (1.62 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 1 mg/mL (1.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.6191 mL 8.0956 mL 16.1912 mL
5 mM 0.3238 mL 1.6191 mL 3.2382 mL
10 mM 0.1619 mL 0.8096 mL 1.6191 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Biological Data
  • LY2584702 Tosylate

    Protein expression of RPS6KB1, p-RPS6KB1, rpS6 and p-rpS6 after the treatment by various LY2584702 concentrations for 24 h.2017 Aug 9;12(8):e0182891.

  • LY2584702 Tosylate

    Proliferation alteration of NSCLC cell lines with RPS6KB1 dephosphorylation by LY2584702 (CCK-8 analysis).2017 Aug 9;12(8):e0182891.

  • LY2584702 Tosylate

    Cell cycle distribution of NSCLC cell lines with RPS6KB1 dephosphorylation by LY2584702.2017 Aug 9;12(8):e0182891.

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