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. 2021 May 27;64(11):7296–7311. doi: 10.1021/acs.jmedchem.0c01313

Table 2. CRBN, GSPT1, and MV4-11 Structure–Activity Relationship (SAR).

graphic file with name jm0c01313_0014.jpg

cmpd R CRBN IC50 (μM)a MV4-11 EC50 (μM)a HEK293 hGSPT1-HiBit EC50 (μM)a sol. (μM)a,b Papp (nm/s)a,c
5 (CC-90009)   0.824 0.062 0.0292 77 49
6 (SJ6986) 2-OCF3 0.015 0.0015 0.0001 67 23
7 (SJ7023) 2-Me, 3-Cl 0.016 0.052 0.108 64 36
8 H 0.003 >10 >10 71 36
9 4-Me, 3-Cl 0.001 >10 >10 ND 46
10 3-OCF3 0.010 >10 >10 64 40
11 4-OCF3 0.009 >10 >10 76 11
12 2-OMe 0.612 >10 >10 85 6
13 2-Me 0.011 7.4 9.32 84 68
14 2-CF3 0.337 0.089 0.052 66 14
15 3-Cl 0.023 >10 >10 74 17
a

All values are the mean of ≥2 independent experiments.

b

Aqueous solubility measured at pH = 7.4 in triplicate.

c

Permeability in MDCK cells. ND = not determined.