Table 1 Biological Activities and DMPK Profiles for 5 and DKY709

CRBN binding^a

IC₅₀ (µM)

0.50

0.12

IKZF2 degradation^b

DC₅₀ (D_max)

1.5 nM (73%)

9.7 nM (70%)

IKZF1 degradation^b

DC₅₀ (D_max)

>10 µM (14%)

>10 µM (5%)

IKZF3 degradation^b

DC₅₀ (D_max)

>10 µM (20%)

>10 µM (7%)

SALL4 degradation^b

DC₅₀ (D_max)

4.9 nM (55%)

>1000 nM (33%)

GSPT1 degradation^b

DC₅₀ (D_max)

>10 µM (16%)

>10 µM (0%)

CK1α degradation^b

DC₅₀ (D_max)

>10 µM (15%)

>10 µM (12%)

hERG inhibition

IC₅₀ (µM)

7.1

11

liver microsomal stability (human/rat/mouse)

T_1/2 (min)

>60

>60

Caco-2 Permeability

P_app (10⁻⁶cm/s)

8.1

19

efflux ratio

1.9

1.1

mouse PK profile^c,d

CL (mL/min/kg)^e

48

40

V_ss (L/kg)^e

9.4

4.2

T_1/2 (h) ^f

1.3

2.9

C_max (ng/mL) ^f

273

398

AUC (h*ng/mL) ^f

603

1336

F (%)

64

108

rat PK profile^c,d

CL (mL/min/kg)^e

51

21

V_ss (L/kg)^e

12.6

3.3

T_1/2 (h) ^f

1.3

1.4

C_max (ng/mL) ^f

73

263

AUC (h*ng/mL) ^f

349

1172

F (%)

36

49