SAFit2 |
Catalog No.GC34093
One-Click Copy Product Info
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SAFit2 is a potent inhibitor of FK506-binding protein 51 (FKBP51), with the Ki value of 6nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1643125-33-0
Sample solution is provided at 25 µL, 10mM.
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SAFit2 is a potent inhibitor of FK506-binding protein 51 (FKBP51), with the Ki value of 6nM[1]. SAFit2 can reduce the phosphorylation levels of the inhibitory complex α (IκBα) and p65, as well as decrease the levels of chemokines and cytokines, thereby inhibiting the inflammatory response[2]. SAFit2 has been widely used as a pharmacological probe for FKBP51 to alleviate pain and regulate neuroinflammation in animals[3].
In vitro, SAFit2 treatment (60nM) for 4 days reduced PD-L1 expression and inhibited cell growth in mouse glioblastoma (GBM) cells[4]. Treatment with 1μM SAFit2 for 48 hours can improve the function of isolated mouse β cells and upregulate the mRNA expression levels of Nkx6.1, Mafa, Ins1 and ins2[5].
In vivo, SAFit2 treatment via intraperitoneal injection twice daily at a dose of 10mg/kg for 6 days restored lipid signaling and metabolism in the neural tissue of mice after nerve injury[6]. Administering 10mg/kg SAFit2 by intraperitoneal injection twice a day for 6 consecutive days can alleviate mechanical hyperalgesia induced by paclitaxel in mice[7]. A single intraperitoneal injection of 20mg/kg SAFit2, administered over a period of 4 hours, reduced the anxiety-like behaviors in female rats during the early stage of cocaine self-administration withdrawal[8].
References:
[1] Gaali S, Feng X, Hähle A, et al. Rapid, structure-based exploration of pipecolic acid amides as novel selective antagonists of the FK506-binding protein 51[J]. Journal of medicinal chemistry, 2016, 59(6): 2410-2422.
[2] Buffa V, Knaup F H, Heymann T, et al. Analysis of the selective antagonist SAFit2 as a chemical probe for the FK506-binding protein 51[J]. ACS Pharmacology & Translational Science, 2023, 6(3): 361-371.
[3] Si Y, Zhao X, Wu L, et al. Inhibition of the NFATc2/FKBP5 axis alleviates microglial neuroinflammation by regulating arachidonic acid metabolism in Parkinson’s disease[J]. Brain, Behavior, and Immunity, 2026: 106296.
[4] D’Arrigo P, Digregorio M, Romano S, et al. The splicing FK506-binding protein-51 isoform plays a role in glioblastoma resistance through programmed cell death ligand-1 expression regulation[J]. Cell Death Discovery, 2019, 5(1): 137.
[5] Liu N, Li R, Cao J, et al. The inhibition of FKBP5 protects β-cell survival under inflammation stress via AKT/FOXO1 signaling[J]. Cell death discovery, 2023, 9(1): 247.
[6] Wedel S, Hahnefeld L, Alnouri M W, et al. The FKBP51 inhibitor SAFit2 restores the pain-relieving C16 dihydroceramide after nerve injury[J]. International journal of molecular sciences, 2022, 23(22): 14274.
[7] Wedel S, Hahnefeld L, Schreiber Y, et al. SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators[J]. Journal of neuroinflammation, 2023, 20(1): 149.
[8] Connelly K L, Wolsh C C, Barr J L, et al. Sex differences in the effect of the FKBP5 inhibitor SAFit2 on anxiety and stress-induced reinstatement following cocaine self-administration[J]. Neurobiology of stress, 2020, 13: 100232.
| Cell experiment [1]: | |
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Cell lines |
ICR mouse pancreatic β cells |
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Preparation Method |
ICR mouse pancreatic β cells were grown in DMEM medium supplemented with 10% fetal bovine serum, 100U/ml penicillin, and 0.1mg/ml streptomycin in 5% CO2 at 37°C. Cells were treated with DMSO or SAFit2 (1μM) for 48h and the mRNA expression levels of Nkx6.1, Mafa, Ins1 and ins2 were analyzed. |
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Reaction Conditions |
1μM; 48h |
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Applications |
SAFit2 treatment significantly enhanced the levels of Nkx6.1, Mafa, Ins1 and ins2 in mouse pancreatic β cells. |
| Animal experiment [2]: | |
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Animal models |
C57Bl/6N mice |
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Preparation Method |
Male C57Bl/6N mice (8 weeks old) were kept in temperature-controlled (21°C-25°C) and humidity-maintained (40%-70%) room with a 12-h light/dark cycle. Water and food were provided freely. For inducing neuropathic pain in mice, a spared nerve injury (SNI) surgery was performed under anesthesia to establish neuroinflammation. During the surgery, the sciatic nerve was exposed by a blunt dissection at the level of the knee joint. Then, two of the three sciatic nerve branches, the common peroneal and tibial branches, were ligated with 6/0 non-sterile silk thread and cut distally from the ligature, leaving the sural nerve branch intact. Contact with the sural nerve branch was avoided to prevent stretching or harm. Afterwards, the muscle and skin are closed in two layers. Mice were treated intraperitoneally with either 10mg/kg SAFit2 or vehicle (PBS supplemented with 5% PEG400, 5% Tween and 0.7% ethanol) twice daily on six consecutive days starting on day five after surgery. For the determination of the mechanical withdrawal threshold, a dynamic plantar test was used. |
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Dosage form |
10mg/kg; twice a day for 6 days; i.p. |
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Applications |
SAFit2 treatment reduced nerve injury-induced mechanical hypersensitivity in mice. |
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References: |
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| Cas No. | 1643125-33-0 | SDF | |
| Canonical SMILES | O=C(N1[C@@H](CCCC1)C(O[C@@H](C2=CC(OCCN3CCOCC3)=CC=C2)CCC4=CC(OC)=C(OC)C=C4)=O)[C@@H](C5CCCCC5)C6=CC(OC)=C(OC)C(OC)=C6 | ||
| Formula | C46H62N2O10 | M.Wt | 802.99 |
| Solubility | DMSO : 125 mg/mL (155.67 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 | 1.2453 mL | 6.2267 mL | 12.4535 mL |
| 5 mM | 249.1 μL | 1.2453 mL | 2.4907 mL |
| 10 mM | 124.5 μL | 622.7 μL | 1.2453 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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 saline, 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
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 24 reference(s) in Google Scholar.)