Synonym
SAFit1; SA-Fit-1; SAF-it-1; SAF it 1; SA Fit 1;
IUPAC/Chemical Name
2-(3-((R)-1-((S)-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl)piperidine-2-carbonyloxy)-3-(3,4-dimethoxyphenyl)propyl)phenoxy)acetic acid
InChi Key
OEQZPFWOEOOISR-AKTKKGGCSA-N
InChi Code
InChI=1S/C42H53NO11/c1-48-34-20-18-27(22-35(34)49-2)17-19-33(29-14-11-15-31(23-29)53-26-38(44)45)54-42(47)32-16-9-10-21-43(32)41(46)39(28-12-7-6-8-13-28)30-24-36(50-3)40(52-5)37(25-30)51-4/h11,14-15,18,20,22-25,28,32-33,39H,6-10,12-13,16-17,19,21,26H2,1-5H3,(H,44,45)/t32-,33+,39-/m0/s1
SMILES Code
O=C(O)COC1=CC=CC([C@H](OC([C@H]2N(C([C@@H](C3CCCCC3)C4=CC(OC)=C(OC)C(OC)=C4)=O)CCCC2)=O)CCC5=CC=C(OC)C(OC)=C5)=C1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
SAFit1 is a FK506 binding protein 51 (FKBP51)-specific inhibitor with a Ki of 4±0.3 nM.
In vitro activity:
SAFit1 may hold promise as a therapeutic intervention to modulate the activity of FKBP51, potentially addressing glucocorticoid-induced insulin resistance. When human subcutaneous adipose tissue (SAT) samples were incubated with SAFit1, it exhibited the ability to partially counteract the detrimental effects of the synthetic glucocorticoid dexamethasone. SAFit1 played a role in mitigating the impairment of glucose uptake caused by glucocorticoids.
Reference: Endocrine. 2018 Oct;62(1):116-128. https://pubmed.ncbi.nlm.nih.gov/30032404/
In vivo activity:
This paper presents the development and validation data of an LC-MS/MS method for the simultaneous quantitation of SAFit1 and SAFit2 in mice plasma as per FDA regulatory guidelines. In mouse plasma, SAFit1 displayed a linear concentration range. SAFit1 exhibited stability under various conditions and was successfully applied in mice.
Reference: Drug Res (Stuttg). 2020 Jul;70(7):325-332. https://pubmed.ncbi.nlm.nih.gov/32403135/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
747.88
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Sidibeh CO, Pereira MJ, Abalo XM, J Boersma G, Skrtic S, Lundkvist P, Katsogiannos P, Hausch F, Castillejo-López C, Eriksson JW. 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. doi: 10.1007/s12020-018-1674-5. Epub 2018 Jul 21. PMID: 30032404; PMCID: PMC6153563.
2. Gaali S, Kirschner A, Cuboni S, Hartmann J, Kozany C, Balsevich G, Namendorf C, Fernandez-Vizarra P, Sippel C, Zannas AS, Draenert R, Binder EB, Almeida OF, Rühter G, Uhr M, Schmidt MV, Touma C, Bracher A, Hausch F. Selective inhibitors of the FK506-binding protein 51 by induced fit. Nat Chem Biol. 2015 Jan;11(1):33-7. doi: 10.1038/nchembio.1699. Epub 2014 Dec 1. PMID: 25436518.
3. Gabani BB, Sulochana SP, Siddesh AHA, Kiran V, Saini NK, Samanta SK, Hallur MS, Rajagopal S, Mullangi R. 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. doi: 10.1055/a-1164-6123. Epub 2020 May 13. PMID: 32403135.
In vitro protocol:
1. Sidibeh CO, Pereira MJ, Abalo XM, J Boersma G, Skrtic S, Lundkvist P, Katsogiannos P, Hausch F, Castillejo-López C, Eriksson JW. 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. doi: 10.1007/s12020-018-1674-5. Epub 2018 Jul 21. PMID: 30032404; PMCID: PMC6153563.
2. Gaali S, Kirschner A, Cuboni S, Hartmann J, Kozany C, Balsevich G, Namendorf C, Fernandez-Vizarra P, Sippel C, Zannas AS, Draenert R, Binder EB, Almeida OF, Rühter G, Uhr M, Schmidt MV, Touma C, Bracher A, Hausch F. Selective inhibitors of the FK506-binding protein 51 by induced fit. Nat Chem Biol. 2015 Jan;11(1):33-7. doi: 10.1038/nchembio.1699. Epub 2014 Dec 1. PMID: 25436518.
In vivo protocol:
1. Gabani BB, Sulochana SP, Siddesh AHA, Kiran V, Saini NK, Samanta SK, Hallur MS, Rajagopal S, Mullangi R. 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. doi: 10.1055/a-1164-6123. Epub 2020 May 13. PMID: 32403135.
1: Buffa V, Meyners C, Sugiarto WO, Bauder M, Gaali S, Hausch F. 1,4-Pyrazolyl- Containing SAFit-Analogues are Selective FKBP51 Inhibitors With Improved Ligand Efficiency and Drug-Like Profile. ChemMedChem. 2024 Sep 2;19(17):e202400264. doi: 10.1002/cmdc.202400264. Epub 2024 Jul 8. PMID: 38818693.
2: Gabani BB, Sulochana SP, Siddesh AHA, Kiran V, Saini NK, Samanta SK, Hallur MS, Rajagopal S, Mullangi R. 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. doi: 10.1055/a-1164-6123. Epub 2020 May 13. PMID: 32403135.
3: Sidibeh CO, Pereira MJ, Abalo XM, J Boersma G, Skrtic S, Lundkvist P, Katsogiannos P, Hausch F, Castillejo-López C, Eriksson JW. 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. doi: 10.1007/s12020-018-1674-5. Epub 2018 Jul 21. PMID: 30032404; PMCID: PMC6153563.
4: Gaali S, Kirschner A, Cuboni S, Hartmann J, Kozany C, Balsevich G, Namendorf C, Fernandez-Vizarra P, Sippel C, Zannas AS, Draenert R, Binder EB, Almeida OF, Rühter G, Uhr M, Schmidt MV, Touma C, Bracher A, Hausch F. Selective inhibitors of the FK506-binding protein 51 by induced fit. Nat Chem Biol. 2015 Jan;11(1):33-7. doi: 10.1038/nchembio.1699. Epub 2014 Dec 1. PMID: 25436518.
