SML4123
dTAGV-1
≥98%
Synonym(s):
(R)-3-(3,4-Dimethoxyphenyl)-1-(2-(2-((7-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-7-oxoheptyl)amino)-2-oxoethoxy)phenyl)propyl (S)-1-((S)-2-(3,4,5- trimethoxyphenyl)butanoyl)piperidine-2-carboxylate, BNN-01-004, dTAGv-1
Quality Level
Assay
≥98%
form
powder
color
white to beige
solubility
DMSO: 2 mg/mL, clear
storage temp.
-10 to -25°C
SMILES string
O=C(O[C@H](CCC1=CC=C(C(OC)=C1)OC)C2=CC=CC=C2OCC(NCCCCCCC(N[C@H](C(N3[C@@H](C[C@H](C3)O)C(N[C@@H](C)C4=CC=C(C=C4)C5=C(N=CS5)C)=O)=O)C(C)(C)C)=O)=O)[C@H]6N(CCCC6)C([C@@H](CC)C7=CC(OC)=C(C(OC)=C7)OC)=O
Biochem/physiol Actions
dTAGV-1 is a degradation tag (dTAG) system heterobifunctional degrader composed of an E3 ubiquitin ligase von Hippel-Lindau (VHL)-binding ligand and an FKBP12(F36V) mutant-specific ligand AP1867 void of affinity for endogenous (wild-type) FKBP12, allowing selective degradation of target proteins of interest when expressed as an FKBP12(F36V) in-frame fusion by bridging them with VHL for ubiquitination. dTAGV-1 selectively induces cellular degradation of FKBP12F36V fusions in cultures (50-500 nM for 4-24 hrs) and in mice in vivo (35 mg/kg/day i.p.) with superior half-life and exposure than dTAG-13 (T1/2 = 4.43 vs. 2.41 h, AUC = 18517 vs. 6140 h*ng post 10 mg/kg i.p.).
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