dTAGV-1 TFA

dTAGV-1 TFA is a potent and selective degrader of mutant FKBP12F36V fusion proteins. dTAGV-1 TFA can induce degradation of FKBP12F36V-Nluc in vivo[1].

Research Areas >> Cancer

Signaling Pathways >> PROTAC >> PROTAC

VHL

dTAGV-1 (0.1 nM-10 μM; 24 h) TFA induces potent degradation of FKBP12F36V-Nluc with no effects on FKBP12WT-Nluc in 293FT cells[1]. dTAGV-1 (125-2000 nM; 24 h) TFA co-treatment with THAL-SNS-032 leads to pronounced degradation of both LACZ-FKBP12F36V and CDK9[1]. dTAGV-1 (500 nM; 1-24 h) TFA leads to rapid KRASG12V and pERK1/2 degradation[1]. dTAGV-1 (50-5000 nM; 24 h) TFA enables EWS/FLI degradation in Ewing sarcoma[1].

dTAGV-1 (35 mg/kg; i.p. once daily for 4 days) TFA induces degradation of FKBP12F36V-Nluc in mice[1]. dTAGV-1 (2-10 mg/kg; i.p.) TFA exhbits half-lives (T1/2=3.64 and 4.4 h), Cmax (595 and 2123 ng/mL) and great exposure (AUCinf =3136 and 18517 h•ng/mL) in mice[1]. dTAGV-1 (2 mg/kg; i.v.) TFA exhbits half-life (T1/2=3.02 h), Cmax (7780 ng/mL) and great exposure (AUCinf =3329 h•ng/mL) in mice[1]. Animal Model: 8-week-old immunocompromised female mice were transplanted with MV4;11 luc-FKBP12F36V cells[1] Dosage: 35 mg/kg Administration: I.p. once daily for 4 days Result: Observed striking loss of bioluminescent signal 4 h after the first and three administrations. Degradation evident 28 h after the final administration.

[1]. Nabet B, et, al. Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules. Nat Commun. 2020 Sep 18;11(1):4687.