FKBP12 PROTAC dTAG-13

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FKBP12 PROTAC dTAG-13 (dTAG-13) 是一种体内活性异双功能标签 (dTAG) 小分子，可与 FKBP12F36V 和 CRBN 结合。

FKBP12 PROTAC dTAG-13 (dTAG-13) is an in vivo-active heterobifunctional adation tag (dTAG) small molecule that engage FKBP12F36V and CRBN, selectively degrade FKBP12F36V in a CRBN-dependent manner in cells; causes rapid degradation of nuclear and cytoplasmic FKBP12F36V fusion chimeras, and 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.

TAG-13 (1-1000 nM; 4 hours; 293FTWT cells) treatment potently reduces FKBP12F36V-Nluc levels in 293FTWT cell, indicating the requirement of CRBN for the observed effects.Treatment of MV4;11 cells expressing BRD4(short)-FKBP12F36V with dTAG-13 leads to robust degradation of BRD4. dTAG-13 treatment leads to rapid degradation of BRD4 within one hou. dTAG-13 treatment leads to rapid and potent degradation of the BRD4 fusion chimera in the heterozygous and homozygous knock-in clones, with no effect on endogenous FKBP12WT. Western Blot Analysis Cell Line:293FTWT cells Concentration:1 nM, 10 nM, 100 nM, 1000 nM Incubation Time:4 hours Result:Potently reduced FKBP12F36V-Nluc levels in 293FTWT cell.

Following bone marrow engraftment of MV4;11 cells expressing luc-FKBP12F36V in mice, the bioluminescent signal after vehicle or dTAG-13 administration is monitored. A significant, rapid, and durable effect on bioluminescent signal is observed four hours after dTAG-13 administration, indicating effective degradation of luc-FKBP12F36V. Twenty-eight hours following the final treatment, the recovery of cellular bioluminescence to levels comparable between vehicle and dTAG-13 treatment groups is observed.

dTAG-13

PROTACs

PROTAC

PROTAC

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2064175-41-1

1049.184

C57H68N4O15

>98% (HPLC)

In Vitro:?DMSO : ≥ 100 mg/mL (95.31 mM)

CCC(C1=CC(=C(C(=C1)OC)OC)OC)C(=O)N2CCCCC2C(=O)OC(CCC3=CC(=C(C=C3)OC)OC)C4=CC=CC=C4OCC(=O)NCCCCCCOC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O

(1R)-3-(3,4-dimethoxyphenyl)-1-(2-(2-((6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)hexyl)amino)-2-oxoethoxy)phenyl)propyl (2S)-1-((S)-2-(3,4,5-trimethoxyphenyl)butanoyl)piperidine-2-carboxylate

(-20℃)

With Ice Pack

≥ 2 years