| Identification | Back Directory | [Name]
SAfit2 | [CAS]
1643125-33-0 | [Synonyms]
SAfit2
2-Piperidinecarboxylic acid, 1-[(2S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl]-, (1R)-3-(3,4-dimethoxyphenyl)-1-[3-[2-(4-morpholinyl)ethoxy]phenyl]propyl ester, (2S)- | [Molecular Formula]
C46H62N2O10 | [MDL Number]
MFCD31619236 | [MOL File]
1643125-33-0.mol | [Molecular Weight]
802.99 |
| Chemical Properties | Back Directory | [Boiling point ]
877.0±65.0 °C(Predicted) | [density ]
1.168±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 50 mg/ml; DMSO: 50 mg/ml; DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml; Ethanol: 10 mg/ml | [form ]
A crystalline solid | [pka]
6.43±0.10(Predicted) | [color ]
Off-white to pink | [InChIKey]
ZDBWLRLGUBSLPG-FDHYQTMZSA-N | [SMILES]
N1(C([C@@H](C2CCCCC2)C2=CC(OC)=C(OC)C(OC)=C2)=O)CCCC[C@H]1C(O[C@@H](C1=CC=CC(OCCN2CCOCC2)=C1)CCC1=CC=C(OC)C(OC)=C1)=O |
| Hazard Information | Back Directory | [Description]
SAfit2 is a potent inhibitor of FK506-binding protein 51 (FKBP51; Ki = 6 nM). It is highly selective for FKBP51 over FKBP52 (Ki = >50,000 nM) and has increased brain permeability in comparison to SAfit1. SAfit2 (20 mg/kg) enhances HPA axis suppression in mice by decreasing plasma corticosterone levels to a greater extent than in control mice following dexamethasone administration. It also does not increase plasma corticosterone levels as high as in control mice following subsequent administration of corticotropin-releasing factor (CRF; ). It decreases the time spent immobile in the forced swim test and increases the time spent in the open arms of the elevated plus maze, indicating antidepressant-like and anxiolytic-like activity, respectfully. | [Uses]
SAFit2 is a highly selective inhibitor of FKBP51. The selective inhibition of FKBP51, using SAFit1(S139583) & SAFit2 , has shown to enhances neurite elongation in neuronal cultures and improves neuroendocrine feedback and stress-coping behavior in mice. | [in vivo]
It is found that 30 days of SAFit2 administration leads to a reduction in body weight under both control and high-fat diet (HFD) conditions. SAFit2 significantly increases phosphorylated AKT2 and AS160 in EDL muscle and likewise increases expression of GLUT4 at the membrane in soleus muscle[2]. When SAFit2 is applied 1 h before testing, no alterations in anxiety-related behavior are observed. However, SAFit2 treatment induces an anxiolytic phenotype in mice injected 16 h prior testing, which is reflected in a significantly increased open arm time in the elevated plus maze (EPM) (z=-2.183, p<0.05).? SAFit2 treatment leads to a significantly reduced latency to enter the lit compartment (z=-2 to 265, p<0.05), as well as a significantly increased distance traveled (t(20)=-2.371, p<0.05) in the lit compartment[3]. | [References]
[1] STEFFEN GAALI. Selective inhibitors of the FK506-binding protein 51 by induced fit[J]. Nature chemical biology, 2014, 11 1: 33-37. DOI: 10.1038/nchembio.1699
[2] JAKOB HARTMANN. Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic Properties.[J]. Journal of Neuroscience, 2015, 35 24: 9007-9016. DOI: 10.1523/jneurosci.4024-14.2015 |
|
|