Name: FKBP12 PROTAC dTAG-7
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO, Ethanol

Appearance

Off-white Solid

Storage

Store at -20°C

Shipping

Room temperature in continental US; may vary elsewhere.

IUPACName

[(1R)-3-(3,4-dimethoxyphenyl)-1-[2-[2-[3-[2-[2-[3-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-2-oxoethoxy]phenyl]propyl] (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carboxylate

Synonyms

(1R)-3-(3,4-Dimethoxyphenyl)-1-(2-((19-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)-2,18-dioxo-7,10,13-trioxa-3,17-diazanonadecyl)oxy)phenyl)propyl (2S)-1-((S)-2-(3,4,5-trimethoxyphenyl)butanoyl)piperidine-2-carboxylate; 2-Piperidinecarboxylic acid, 1-[(2S)-1-oxo-2-(3,4,5-trimethoxyphenyl)butyl]-, (1R)-3-(3,4-dimethoxyphenyl)-1-[2-[[19-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]-2,18-dioxo-7,10,13-trioxa-3,17-diazanonadec-1-yl]oxy]phenyl]propyl ester, (2S)-; (1R)-3-(3,4-Dimethoxyphenyl)-1-[2-[[19-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]-2,18-dioxo-7,10,13-trioxa-3,17-diazanonadec-1-yl]oxy]phenyl]propyl (2S)-1-[(2S)-1-oxo-2-(3,4,5-trimethoxyphenyl)butyl]-2-piperidinecarboxylate; dTAG-7

Boiling Point

1242.1±65.0°C at 760 Torr

Density

1.265±0.06 g/cm3

InChI Key

IFCAWDLUIZXIPI-FJDAOBEISA-N

InChI

InChI=1S/C63H79N5O19/c1-7-42(41-36-52(79-4)58(81-6)53(37-41)80-5)60(73)67-28-11-10-17-46(67)63(76)87-48(23-20-40-21-24-49(77-2)51(35-40)78-3)43-15-8-9-18-47(43)85-38-55(70)64-26-13-29-82-31-33-84-34-32-83-30-14-27-65-56(71)39-86-50-19-12-16-44-57(50)62(75)68(61(44)74)45-22-25-54(69)66-59(45)72/h8-9,12,15-16,18-19,21,24,35-37,42,45-46,48H,7,10-11,13-14,17,20,22-23,25-34,38-39H2,1-6H3,(H,64,70)(H,65,71)(H,66,69,72)/t42-,45?,46-,48+/m0/s1

SMILES

O=C(OC(C=1C=CC=CC1OCC(=O)NCCCOCCOCCOCCCNC(=O)COC2=CC=CC=3C(=O)N(C(=O)C23)C4C(=O)NC(=O)CC4)CCC5=CC=C(OC)C(OC)=C5)C6N(C(=O)C(C7=CC(OC)=C(OC)C(OC)=C7)CC)CCCC6

Pub Chem ID

131954816

Mechanism

Target: dTAG-7 targets FKBP12F36V fusion proteins and BET bromodomain protein BRD4.

Binding site: Its FKBP ligand binds FKBP12F36V, while its BET ligand binds BRD4 bromodomains.

Mechanism of action: FKBP12 PROTAC dTAG-7 is a heterobifunctional degrader used for chemical control of FKBP12F36V-tagged proteins and also described as a BRD4 degrader. In dTAG applications, the compound engages FKBP12F36V fused in-frame with a protein of interest and recruits CRBN, resulting in rapid, selective ubiquitination and proteasomal degradation of the tagged target. Because it can also connect BET bromodomains to cereblon, experimental interpretation should consider BRD4 degradation where relevant. dTAG-7 supports target validation, acute depletion studies, and comparison of tag-based versus endogenous BET degradation phenotypes.

Applications

• PROTAC-Mediated FKBP12 Degradation: FKBP12 PROTAC dTAG-7 facilitates the targeted degradation of the FKBP12 protein, enabling researchers to study its role in cellular processes. By inducing proteasomal degradation, this PROTAC offers a powerful tool for dissecting FKBP12's involvement in signal transduction and cellular homeostasis.

• Targeted Degradation in Drug Discovery: Utilizing FKBP12 PROTAC dTAG-7 can accelerate drug discovery efforts by allowing precise modulation of FKBP12 levels. Researchers can explore therapeutic targets and validate drug mechanisms through controlled protein degradation, enhancing the understanding of FKBP12-related pathways.

• Functional Genomics with PROTACs: FKBP12 PROTAC dTAG-7 serves as a valuable asset in functional genomics studies. By specifically degrading FKBP12, scientists can identify downstream effects and elucidate gene functions, advancing knowledge of complex biological systems and their regulatory networks.

• PROTACs in Signal Pathway Analysis: The use of FKBP12 PROTAC dTAG-7 enables detailed analysis of signaling pathways involving FKBP12. By selectively removing this protein, researchers can map out pathway interactions and dynamics, contributing to a deeper understanding of cellular signaling mechanisms.

1. The dTAG system for immediate and target-specific protein degradation.

Nabet, B., Roberts, J.M., Buckley, D.L., Paulk, J., Dastjerdi, S., Yang, A., Leggett, A.L., Erb, M.A., Lawlor, M.A., Souza, A. and Scott, T.G., 2018. Nature chemical biology, 14(5), pp.431-441.

Dissection of complex biological systems requires target-specific control of the function or abundance of proteins. Genetic perturbations are limited by off-target effects, multicomponent complexity, and irreversibility. Most limiting is the requisite delay between modulation to experimental measurement. To enable the immediate and selective control of single protein abundance, we created a chemical biology system that leverages the potency of cell-permeable heterobifunctional degraders. The dTAG system pairs a novel degrader of FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. By transgene expression or CRISPR-mediated locus-specific knock-in, we exemplify a generalizable strategy to study the immediate consequence of protein loss. Using dTAG, we observe an unexpected superior antiproliferative effect of pan-BET bromodomain degradation over selective BRD4 degradation, characterize immediate effects of KRASG12V loss on proteomic signaling, and demonstrate rapid degradation in vivo. This technology platform will confer kinetic resolution to biological investigation and provide target validation in the context of drug discovery.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	0.83 mL	4.13 mL	8.26 mL
5 mM	0.17 mL	0.83 mL	1.65 mL
10 mM	0.08 mL	0.41 mL	0.83 mL
50 mM	0.02 mL	0.08 mL	0.17 mL

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂