Name: dFKBP-1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥98%

Solubility

Soluble in DMSO

Storage

Store at 2-8°C, stored under nitrogen

IUPACName

[(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

Synonyms

(1R)-3-(3,4-Dimethoxyphenyl)-1-(3-{[4-({4-[({[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]oxy}acetyl)amino]butyl}amino)-4-oxobutanoyl]amino}phenyl)propyl (2S)-1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidinecarboxylate; 2-Piperidinecarboxylic acid, 1-(3,3-dimethyl-1,2-dioxopentyl)-, (1R)-3-(3,4-dimethoxyphenyl)-1-[3-[[4-[[4-[[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]acetyl]amino]butyl]amino]-1,4-dioxobutyl]amino]phenyl]propyl ester, (2S)-

Density

1.3±0.1 g/cm3

InChI Key

RIBCWKRMNKOGRN-GGJINPDOSA-N

InChI

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

SMILES

CCC(C)(C)C(=O)C(=O)N1CCCCC1C(=O)OC(CCC2=CC(=C(C=C2)OC)OC)C3=CC(=CC=C3)NC(=O)CCC(=O)NCCCCNC(=O)COC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=O

Mechanism

Target: dFKBP-1 selectively targets FKBP12, the twelve-kilodalton FK506-binding protein.

Binding site: Its SLF ligand occupies the canonical FK506-binding pocket of FKBP12.

Mechanism of action: dFKBP-1 is a cereblon-recruiting FKBP12 PROTAC composed of the synthetic FKBP ligand SLF, a thalidomide-derived CRBN ligand, and a linker. By engaging FKBP12 and CRBN simultaneously, dFKBP-1 promotes ternary-complex formation with CRL4CRBN, leading to FKBP12 ubiquitination and proteasome-dependent degradation. This degradation-based mechanism enables functional interrogation of FKBP12 protein abundance rather than simple ligand occupancy. In research workflows, dFKBP-1 supports studies of immunophilin-associated signaling, degradation kinetics, target selectivity, and cellular consequences of FKBP12 removal from protein interaction networks.

Applications

• PROTAC-Mediated Protein Degradation: dFKBP-1 is utilized in research to facilitate the targeted degradation of proteins by recruiting E3 ligases to specific protein substrates. This enables the study of protein function and regulation by selectively removing proteins of interest from cellular systems.

• Targeted Degradation in Signal Transduction: Researchers employ dFKBP-1 to degrade key signaling proteins, allowing the investigation of signaling pathways and the elucidation of protein roles in cellular communication. This approach aids in understanding complex cellular responses and interactions.

• PROTAC Applications in Cancer Research: dFKBP-1 is applied in cancer research to degrade oncogenic proteins, providing insights into tumor biology and the potential identification of novel therapeutic targets. By selectively degrading cancer-related proteins, researchers can explore new avenues for cancer treatment strategies.

• Investigating Protein Stability: dFKBP-1 is used to study protein stability and turnover, allowing researchers to assess the half-life and degradation pathways of target proteins. This application is crucial for understanding protein dynamics and their implications in various biological processes.

1. Phthalimide conjugation as a strategy for in vivo target protein degradation.

Winter, G.E., Buckley, D.L., Paulk, J., Roberts, J.M., Souza, A., Dhe-Paganon, S. and Bradner, J.E., 2015. Science, 348(6241), pp.1376-1381.

The development of effective pharmacological inhibitors of multidomain scaffold proteins, notably transcription factors, is a particularly challenging problem. In part, this is because many small-molecule antagonists disrupt the activity of only one domain in the target protein. We devised a chemical strategy that promotes ligand-dependent target protein degradation using as an example the transcriptional coactivator BRD4, a protein critical for cancer cell growth and survival. We appended a competitive antagonist of BET bromodomains to a phthalimide moiety to hijack the cereblon E3 ubiquitin ligase complex. The resultant compound, dBET1, induced highly selective cereblon-dependent BET protein degradation in vitro and in vivo and delayed leukemia progression in mice. A second series of probes resulted in selective degradation of the cytosolic protein FKBP12. This chemical strategy for controlling target protein stability may have implications for therapeutically targeting previously intractable proteins.

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