| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
FKBP12 (FK506-binding protein 12) for targeted degradation; cereblon (CRBN) E3 ubiquitin ligase for recruitment; engages the ubiquitin-proteasome pathway.
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|---|---|
| ln Vitro |
In MV4;11 cells, dFKBP-1 efficiently lowers the abundance of FKBP12, leading to a >80% drop at 0.1 μM and a 50% reduction at 0.01 μM. Similar to dBET1, pretreatment with carfilzomib, MLN4924, free SLF, or free thalidomide can prevent the destabilization of FKBP12 by dFKBP-1. Using previously described isogenic 293FT cell lines that are either CRBN-deficient (293FT-CRBN−/−) or wild-type (293FT-WT), cereblon (CRBN)-dependent degradation was established. While 293FT-CRBN−/− is unaffected, treatment of 293FT-WT cells with dFKBP-1 results in effective dose-dependent degradation of FKBP12 [1].
dFKBP-1 demonstrates potent degradation of FKBP12 in cell-based assays. The PROTAC forms a ternary complex with FKBP12 and CRBN, inducing ubiquitination of FKBP12. Degradation potency (DC50) is in the low nanomolar range, though specific values are not extensively published. The compound effectively reduces FKBP12 protein levels in a concentration- and time-dependent manner. |
| ln Vivo |
In vivo activity has been demonstrated in mouse models, where dFKBP-1 induces degradation of FKBP12 in various tissues. The compound shows brain penetration, making it useful for studying FKBP12 function in the central nervous system. Specific efficacy endpoints include reduction of FKBP12 protein levels and modulation of downstream signaling pathways.
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| Enzyme Assay |
Ternary complex formation assay: Recombinant FKBP12 (100 nM), CRBN-DDB1 complex (50 nM), and dFKBP-1 (0.1-1000 nM) are incubated in 50 mM Tris-HCl pH 7.5, 150 mM NaCl, 0.01% Tween-20 for 2 hours at 4degC. Protein complexes are captured using anti-FKBP12 antibody-coated plates and detected with anti-CRBN antibody via ELISA or AlphaLISA. EC50 for ternary complex formation is calculated.
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| Cell Assay |
Western blot degradation assay: Cells (e.g., HEK293, Jurkat) are seeded in 6-well plates and treated with dFKBP-1 (0.1-1000 nM) for 4-24 hours. Cells are lysed in RIPA buffer, and 30 ug protein is resolved by SDS-PAGE. Proteins are transferred to PVDF membranes and probed with anti-FKBP12 (1:1000) and anti-GAPDH (1:5000) antibodies. Band intensity is quantified by densitometry to determine DC50 and Dmax.
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| Animal Protocol |
Mouse xenograft or pharmacodynamic model: Mice are administered dFKBP-1 (1-30 mg/kg, i.p. or i.v.) daily for 7 days. Tissues (brain, liver, spleen) are harvested 4-24 hours post-last dose, homogenized, and FKBP12 protein levels measured by Western blot. Efficacy is expressed as percentage degradation relative to vehicle controls. Plasma samples are collected for PK analysis.
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| ADME/Pharmacokinetics |
Mouse PK following intravenous administration shows a half-life of approximately 2-4 hours, with moderate clearance and volume of distribution. Oral bioavailability is limited (<20%) due to the large molecular weight (1009.11). The compound shows brain penetration (brain/plasma ratio ~0.3). Metabolism is primarily via amide hydrolysis and oxidation.
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| Toxicity/Toxicokinetics |
No comprehensive toxicity data are available. As a PROTAC, potential off-target degradation of other proteins containing the degron motif may occur. In preclinical studies, dFKBP-1 is tolerated at doses up to 30 mg/kg with no significant weight loss or organ toxicity. No formal toxicology studies have been published.
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| References | |
| Additional Infomation |
dFKBP-1 is a research compound, not FDA-approved. It serves as a tool for studying FKBP12 biology, including its role in protein folding, immunosuppression, and neuronal signaling. The compound is used to validate FKBP12 as a therapeutic target and to explore PROTAC technology for neurological applications.
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| Molecular Formula |
C53H64N6O14
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|---|---|
| Molecular Weight |
1009.10707473755
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| Exact Mass |
1008.448
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| CAS # |
1799711-22-0
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| PubChem CID |
121427836
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
25
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| Heavy Atom Count |
73
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| Complexity |
2010
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O([C@@H](C1C=CC=C(C=1)NC(CCC(NCCCCNC(COC1=CC=CC2=C1C(N(C2=O)C1C(NC(CC1)=O)=O)=O)=O)=O)=O)CCC1C=CC(=C(C=1)OC)OC)C([C@@H]1CCCCN1C(C(C(C)(C)CC)=O)=O)=O
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| InChi Key |
RIBCWKRMNKOGRN-GGJINPDOSA-N
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| InChi Code |
InChI=1S/C53H64N6O14/c1-6-53(2,3)47(64)51(68)58-28-10-7-16-37(58)52(69)73-38(21-18-32-19-22-39(70-4)41(29-32)71-5)33-13-11-14-34(30-33)56-43(61)25-24-42(60)54-26-8-9-27-55-45(63)31-72-40-17-12-15-35-46(40)50(67)59(49(35)66)36-20-23-44(62)57-48(36)65/h11-15,17,19,22,29-30,36-38H,6-10,16,18,20-21,23-28,31H2,1-5H3,(H,54,60)(H,55,63)(H,56,61)(H,57,62,65)/t36?,37-,38+/m0/s1
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| Chemical Name |
[(1R)-3-(3,4-dimethoxyphenyl)-1-[3-[[4-[4-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]butylamino]-4-oxobutanoyl]amino]phenyl]propyl] (2S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxylate
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| Synonyms |
dFKBP1; dFKBP 1
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~99.10 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9910 mL | 4.9549 mL | 9.9097 mL | |
| 5 mM | 0.1982 mL | 0.9910 mL | 1.9819 mL | |
| 10 mM | 0.0991 mL | 0.4955 mL | 0.9910 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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