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SAFit2

2D structure
Target FKBP5 
Targeted domain FKBP-type domain 1 (Phe67)
Mode of action Inhibitor
Control ddSAFit2 ,  18(S)-Me
Recommended cellular usage concentration ≥ 5 µM
In vivo use Yes
Synonyms Selective Antagonist of FKBP51 by induced fit 2
Donated by TU Darmstadt


Probe criteria


Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) Surpasses criterion: Kd = 6 ± 2 nM (competitive fluorescence polarization (FP) assay
Selectivity within target family: > 30-fold Competitive fluorescence polarization assay: FKBP1B (Kd = 38.9 ± 3.0 nM); FKBP1A (Kd = 116.4 ± 7.1 nM); FKBP2 (Kd = 1053 ± 93 nM); FKBP4 (Kd > 50 μM); FKBP3 (Kd > 10 μM)
NanoBRET assay (HEK293T cell line FKBP51-NLuc): FKBP1A (IC50 = 1103 ± 86 nM); NanoBRET assay (FKBP12-NLuc): FKBP1B (IC50= 80 ± 21 nM); FKBP4 (IC50 = 1409 ± 92 nM); FKBP1A (IC50 = 771 ± 115 nM)
Selectivity outside target family PDSP scan (45 targets at 10 μM): Off-targets are TMEM97 (Ki =226 nM) and HRH4 (Ki = 3.5 μM)
On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 Surpasses criterion: NanoBRET assay (FKBP12-NLuc): FKBP5 (IC50 = 195.5 ± 14 nM); NanoBRET assay (FKBP51-NLuc): FKBP5 (IC50 = 493 ± 101 nM)
Control compound (100 times less potent than the probe) ddSAFit2: FKBP5 (Kd > 20 μM, FP assay)
18(S)-Me: Ki = 4 ± 2 nM (ITC); FP assay: FKBP5 (Kd = 2.6 nM), FKBP1A (Kd = 0.29 nM), FKBP4 (Kd = 3.6 nM); NanoBRET assay (FKBP51-NLuc): FKBP5 (Ki, app = 14 ± 9 nM )
Closest off-targets in the ddSAFit2 PDSP scan (44 targets) at 10 µM are TMEM97 (Ki = 409.35 nM), SLC6A3 (Ki = 2175.7 nM), SIGMAR1 (Ki = 2852.33 nM) and HRH2 (Ki = 2960.61 nM).