SAFit1 |
| Catalog No.GC33699 |
SAFit1 is a FK506 binding protein 51 (FKBP51)-specific inhibitor with a Ki value of 4 ± 0.3nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1643125-32-9
Sample solution is provided at 25 µL, 10mM.
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SAFit1 is a FK506 binding protein 51 (FKBP51)-specific inhibitor with a Ki value of 4 ± 0.3nM[1]. The selective inhibition of FKBP51 using SAFfit1 has emerged as a possible treatment for chronic pain, obesity-induced diabetes, or depression[2][3].
In vitro, SAFit1 (1-1000nM) effectively stimulated neurite growth in two neuronal cell lines, specifically the mouse N2a line and the human SH-SY5Y line, as well as in primary hippocampal neurons. The active concentration range of SAFit1 is very wide[1]. The NanoBRET assay shows that SAFit1 (1-100000nM) treated HEK293T cells transiently expressing FKBP51-NLuc for 2h dose-dependently competed with a fluorescent NanoBRET tracer, which indicated that SAFit1 was able to engage FKBP51 inside cells. SAFit1 (0.4, 0.2, 1μM) incubated murine microglia SIM-A9 cells for 16h could engage FKBP51 in cells and inhibited IKKα phosphorylation in a dose-dependent manner[4]. A375 melanoma incubated in the presence of 20nM SAFit1 for 5h decreased transcript and protein levels of the receptor type I of TGF-β (TβRI) and reduced the protein expression of phosphorylated (p)-Smad2,3. SAFit1 finally inhibited FKBP51-dependent TGF-β pro-tumoral function in vitro[5].
In vivo, mice received SAFit1 (30mg/kg) and SAFit2 (30mg/kg) as a cassette dose orally in a pharmacokinetic study. The experimental results showed that the maximum concentration (Cmax) of SAFit1 in mice was 1467ng/mL, and the time to reach Cmax was 0.5 hours, indicating that SAFIT1 was absorbed quickly in the gastrointestinal tract[6].
References:
[1] Gaali S, Kirschner A, Cuboni S, et al.Selective inhibitors of the FK506-binding protein 51 by induced fit. Nat Chem Biol. 2015 Jan;11(1):33-7.
[2] Sidibeh C O, Pereira M J, Abalo X M,et al.FKBP5 expression in human adipose tissue: potential role in glucose and lipid metabolism, adipogenesis and type 2 diabetes.Endocrine. 2018 Oct;62(1):116-128.
[3] Knaup F H, Meyners C, Sugiarto W O, et al.Structure-Based Discovery of a New Selectivity-Enabling Motif for the FK506-Binding Protein 51. J Med Chem. 2023 Apr 27;66(8):5965-5980.
[4] Voll A M, Meyners C, Taubert M C, et al. Macrocyclic FKBP51 Ligands Define a Transient Binding Mode with Enhanced Selectivity. Angew Chem Int Ed Engl. 2021 Jun 7; 60(24): 13257-13263.
[5] Marrone L, Giacomo V D, Malasomma C, et al. Exploring the potential of selective FKBP51 inhibitors on melanoma: an investigation of their in vitro and in vivo effects. Cell Death Discov. 2025 Apr 3;11(1):138.
[6] Gabani B B, Sulochana S P, Siddesh A H,et al. Validated LC-MS/MS Method for Simultaneous Quantitation of SAFit-1 and SAFit-2 in Mice Plasma: Application to a Pharmacokinetic Study. Drug Res (Stuttg). 2020 Jul;70(7):325-332.
| Cell experiment [1]: | |
Cell lines | murine microglia SIM-A9 cell |
Preparation Method | For the preparation of whole-cell lysates, confluent SIM-A9 cell cultures treated with the SAFit1 for 16h. Subsequently, supernatants of cell lysis were prepared for an SDS-PAGE system and analyzed by immunoblotting. |
Reaction Conditions | 0.4, 0.2, 1μM; 16h |
Applications | SAFit1 interfered with the cellular functions of FKBP51 and inhibited IKKα phosphorylation. |
| Animal experiment [2]: | |
Animal models | male Balb/C mice |
Preparation Method | Twelve male Balb/C mice were housed at Jubilant Animal House facility (having 12/12h light/dark cycles with controlled humidity and temperature) for seven days before performing pharmacokinetic study. Mice were fasted for 4h (during the fasting period animals had free access to water) on the day of pharmacokinetic study. Mice received SAFit1 (30mg/kg) and SAFit2 (30mg/kg) as a cassette dose orally. Blood samples (100μL) were collected at pre-determined time points (0.083, 0.17, 0.25, 0.5, 1, 2, 4, 8, 10 and 24h) from retro-orbital plexus. |
Dosage form | 30mg/kg; oral administration.; one dose |
Applications | Following oral administration SAFit1 maximum concentration (Cmax) in plasma (1467ng/mL) attained at 0.5h (Tmax, time to reach Cmax) indicating the rapid absorption from gastrointestinal tract. The AUC0-∞ (area under curve from time zero to infinity) was found to be 1851ng × h/mL for SAFit1. |
References: | |
| Cas No. | 1643125-32-9 | SDF | |
| Canonical SMILES | O=C(N1[C@@H](CCCC1)C(O[C@@H](C2=CC(OCC(O)=O)=CC=C2)CCC3=CC(OC)=C(OC)C=C3)=O)[C@@H](C4CCCCC4)C5=CC(OC)=C(OC)C(OC)=C5 | ||
| Formula | C42H53NO11 | M.Wt | 747.87 |
| Solubility | Methanol : 125 mg/mL (167.14 mM);DMSO : 62.5 mg/mL (83.57 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.3371 mL | 6.6857 mL | 13.3713 mL |
| 5 mM | 0.2674 mL | 1.3371 mL | 2.6743 mL |
| 10 mM | 0.1337 mL | 0.6686 mL | 1.3371 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 11 reference(s) in Google Scholar.)
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