PF-4708671P70 S6K1 isoform inhibitor,cell-permeable CAS# 1255517-76-0 |
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1255517-76-0 | SDF | Download SDF |
| PubChem ID | 51371303 | Appearance | Powder |
| Formula | C19H21F3N6 | M.Wt | 390.41 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 33.33 mg/mL (85.37 mM; Need ultrasonic) | ||
| Chemical Name | 2-[[4-(5-ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-6-(trifluoromethyl)-1H-benzimidazole | ||
| SMILES | CCC1=CN=CN=C1N2CCN(CC2)CC3=NC4=C(N3)C=C(C=C4)C(F)(F)F | ||
| Standard InChIKey | FBLPQCAQRNSVHB-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C19H21F3N6/c1-2-13-10-23-12-24-18(13)28-7-5-27(6-8-28)11-17-25-15-4-3-14(19(20,21)22)9-16(15)26-17/h3-4,9-10,12H,2,5-8,11H2,1H3,(H,25,26) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) (Ki = 20 nM; IC50 = 160 nM). Suppresses the S6K1-mediated phosphorylation of S6, Rictor and mTOR in response to IGF1; displays no effect on the activity of RSK and MSK in vivo. Exhibits no significant inhibition of S6K2 or other AGC kinases (e.g. Akt, PKA and ROCK) in vitro. |
PF-4708671 Dilution Calculator
PF-4708671 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.5614 mL | 12.807 mL | 25.6141 mL | 51.2282 mL | 64.0352 mL |
| 5 mM | 0.5123 mL | 2.5614 mL | 5.1228 mL | 10.2456 mL | 12.807 mL |
| 10 mM | 0.2561 mL | 1.2807 mL | 2.5614 mL | 5.1228 mL | 6.4035 mL |
| 50 mM | 0.0512 mL | 0.2561 mL | 0.5123 mL | 1.0246 mL | 1.2807 mL |
| 100 mM | 0.0256 mL | 0.1281 mL | 0.2561 mL | 0.5123 mL | 0.6404 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
PF-4708671 is a cell-permeable and highly specific inhibitor of p70 ribosomal S6 kinase 1 with IC50 value of 160nM [1].
S6K1 is a regulator of various biology processes. The inhibition of S6K1 is regard as a therapeutic for the treatment of cancer and insulin resistance. PF-4708671 is the first reported inhibitor of S6K1. It inhibits the activity of S6K1 in the in vitro assay with Ki value of 20nM. For the isolated S6K1 from HEK293 cell, PF-4708671 shows inhibition with IC50 value of 160nM. The inhibition of S6K1caused by PF-4708671 is much more potent than of other related kinases such as RSK2 and MSK1. Besides that, PF-4708671 prevents S6K1 from phosphorylating its substrates including the ribosomal S6 protein, mTOR and Rictor. In addition, PF-4708671 is found to enhance the phosphorylation of S6K1 at Thr229 and Thr389, results in a subsequent increase of S6K1 activity. Whereas this increased activity is much less than that stimulated by IGF1 [1].
References:
[1] Pearce L, Alton G, Richter D, et al. Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem. J, 2010, 431: 245-255.
- LY 233053
Catalog No.:BCC5771
CAS No.:125546-04-5
- 3',5,5',7-Tetrahydroxy-4',6-dimethoxyflavone
Catalog No.:BCN6136
CAS No.:125537-92-0
- Dracorhodin perchlorate
Catalog No.:BCN2628
CAS No.:125536-25-6
- Testosterone phenylpropionate
Catalog No.:BCC9171
CAS No.:1255-49-8
- SR 8278
Catalog No.:BCC6191
CAS No.:1254944-66-5
- Sibutramine hydrochloride monohydrate
Catalog No.:BCC5251
CAS No.:125494-59-9
- Saclofen
Catalog No.:BCC6580
CAS No.:125464-42-8
- LY2874455
Catalog No.:BCC1723
CAS No.:1254473-64-7
- RQ-00203078
Catalog No.:BCC6419
CAS No.:1254205-52-1
- Acetate gossypol
Catalog No.:BCN5354
CAS No.:12542-36-8
- TCN 238
Catalog No.:BCC7901
CAS No.:125404-04-8
- Cedrelone
Catalog No.:BCN6135
CAS No.:1254-85-9
- UNC0638
Catalog No.:BCC1135
CAS No.:1255580-76-7
- MnTMPyP Pentachloride
Catalog No.:BCC6532
CAS No.:125565-45-9
- Rotigotine hydrochloride
Catalog No.:BCC1908
CAS No.:125572-93-2
- [Leu31,Pro34]-Neuropeptide Y (porcine)
Catalog No.:BCC5716
CAS No.:125580-28-1
- TRX818
Catalog No.:BCC6458
CAS No.:1256037-58-7
- AI-10-49
Catalog No.:BCC3973
CAS No.:1256094-72-0
- RuBi-Nicotine
Catalog No.:BCC7793
CAS No.:1256362-30-7
- Ledipasvir
Catalog No.:BCC1696
CAS No.:1256388-51-8
- CH5424802
Catalog No.:BCC3749
CAS No.:1256580-46-7
- Blinin
Catalog No.:BCN8455
CAS No.:125675-09-4
- 3''-O-acetyl-platyconic acid A
Catalog No.:BCN3319
CAS No.:1256935-28-0
- 2''-O-acetyl-platyconic acid A
Catalog No.:BCN3318
CAS No.:1256935-30-4
PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1.[Pubmed:26381178]
Biochem Biophys Res Commun. 2015 Oct 23;466(3):499-504.
p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis.
The p70S6K Specific Inhibitor PF-4708671 Impedes Non-Small Cell Lung Cancer Growth.[Pubmed:26771549]
PLoS One. 2016 Jan 15;11(1):e0147185.
BACKGROUND: As a serine/threonine protein kinase, p70S6K plays an important role in tumor cells. Evidence has revealed overexpression of p70S6K and phosphorylated p70S6K (p-p70S6K) in various tumor tissues, with these proteins identified as independent prognostic markers in non-small cell lung cancer (NSCLC). In this study, we explored the role of the p70S6K specific inhibitor PF-4708671 in NSCLC. METHODS: Three NSCLC cell lines (A549, SK-MES-1, and NCI-H460) were treated with PF-4708671 at five different concentrations, including 0.1muM, 0.3muM, 1muM, 3muM and 10muM, and protein levels were determined by Western-blot. Then, PF-4708671's effects were assessed both in vitro (cell proliferation, apoptosis, cell cycle distribution, and invasion) and in vivo. RESULTS: The expression levels of p-p70S6K and the downstream effector S6 were significantly reduced by PF-4708671. Diametrically opposite, the downstream protein levels of BAD, Caspase3 and ERK had increased after treatment with PF-4708671. In addition, PF-4708671 drastically inhibited cell proliferation and invasion ability in A549, SK-MES-1 and NCI-H460 cells in vitro, causing cell cycle arrest in G0-G1 phase. Limited effects of PF-4708671 were observed on apoptosis in the three NSCLC cell lines assessed. Importantly, PF-4708671 could inhibit tumorigenesis in nude mice in vivo. CONCLUSION: These findings demonstrated that the p70S6K specific inhibitor PF-4708671 has inhibitory effects on NSCLC tumorigenesis in vitro and in vivo. Therefore, P70S6K should be considered a new potential therapeutic target, and PF-470867 may be used as targeted drug for cancer treatment.
Leukotriene B(4) Metabolism and p70S6 Kinase 1 Inhibitors: PF-4708671 but Not LY2584702 Inhibits CYP4F3A and the omega-Oxidation of Leukotriene B(4) In Vitro and In Cellulo.[Pubmed:28068410]
PLoS One. 2017 Jan 9;12(1):e0169804.
LTB4 is an inflammatory lipid mediator mainly biosynthesized by leukocytes. Since its implication in inflammatory diseases is well recognized, many tools to regulate its biosynthesis have been developed and showed promising results in vitro and in vivo, but mixed results in clinical trials. Recently, the mTOR pathway component p70S6 kinase 1 (p70S6K1) has been linked to LTC4 synthase and the biosynthesis of cysteinyl-leukotrienes. In this respect, we investigated if p70S6K1 could also play a role in LTB4 biosynthesis. We thus evaluated the impact of the p70S6K1 inhibitors PF-4708671 and LY2584702 on LTB4 biosynthesis in human neutrophils. At a concentration of 10 muM, both compounds inhibited S6 phosphorylation, although neither one inhibited the thapsigargin-induced LTB4 biosynthesis, as assessed by the sum of LTB4, 20-OH-LTB4, and 20-COOH-LTB4. However, PF-4708671, but not LY2584702, inhibited the omega-oxidation of LTB4 into 20-OH-LTB4 by intact neutrophils and by recombinant CYP4F3A, leading to increased LTB4 levels. This was true for both endogenously biosynthesized and exogenously added LTB4. In contrast to that of 17-octadecynoic acid, the inhibitory effect of PF-4708671 was easily removed by washing the neutrophils, indicating that PF-4708671 was a reversible CYP4F3A inhibitor. At optimal concentration, PF-4708671 increased the half-life of LTB4 in our neutrophil suspensions by 7.5 fold, compared to 5 fold for 17-octadecynoic acid. Finally, Michaelis-Menten and Lineweaver-Burk plots indicate that PF-4708671 is a mixed inhibitor of CYP4F3A. In conclusion, we show that PF-4708671 inhibits CYP4F3A and prevents the omega-oxidation of LTB4 in cellulo, which might result in increased LTB4 levels in vivo.
Protective effects of PF-4708671 against N-methyl-d-aspartic acid-induced retinal damage in rats.[Pubmed:27371338]
Fundam Clin Pharmacol. 2016 Dec;30(6):529-536.
We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Rapamycin inhibits mTOR activity, thereby preventing the phosphorylation of ribosomal protein S6, which is a downstream target of S6 kinase. Therefore, we aimed to determine whether PF-4708671, an inhibitor of S6 kinase, protects against NMDA-induced retinal injury. Intravitreal injection of NMDA (200 nmol/eye) caused cell loss in the ganglion cell layer and neuroinflammatory responses, such as an increase in the number of CD45-positive leukocytes and Iba1-positive microglia. Surprisingly, simultaneous injection of PF-4708671 (50 nmol/eye) with NMDA significantly attenuated these responses without affecting phosphorylated S6 levels. These results suggest that PF-4708671 and rapamycin likely protect against NMDA-induced retinal damage via distinct pathways. The neuroprotective effect of PF-4708671 is unlikely to be associated with inhibition of the S6 kinase, even though PF-4708671 is reported to be a S6 kinase inhibitor.
Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1).[Pubmed:20704563]
Biochem J. 2010 Oct 15;431(2):245-55.
S6K1 (p70 ribosomal S6 kinase 1) is activated by insulin and growth factors via the PI3K (phosphoinositide 3-kinase) and mTOR (mammalian target of rapamycin) signalling pathways. S6K1 regulates numerous processes, such as protein synthesis, growth, proliferation and longevity, and its inhibition has been proposed as a strategy for the treatment of cancer and insulin resistance. In the present paper we describe a novel cell-permeable inhibitor of S6K1, PF-4708671, which specifically inhibits the S6K1 isoform with a Ki of 20 nM and IC50 of 160 nM. PF-4708671 prevents the S6K1-mediated phosphorylation of S6 protein in response to IGF-1 (insulin-like growth factor 1), while having no effect upon the PMA-induced phosphorylation of substrates of the highly related RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase) kinases. PF-4708671 was also found to induce phosphorylation of the T-loop and hydrophobic motif of S6K1, an effect that is dependent upon mTORC1 (mTOR complex 1). PF-4708671 is the first S6K1-specific inhibitor to be reported and will be a useful tool for delineating S6K1-specific roles downstream of mTOR.
