. 2019 Apr 12;62(11):5298–5311. doi: 10.1021/acs.jmedchem.9b00058

Table 4. Summary of Compound 11 Secondary Pharmacology Screen Outcomes.

screen	results
Kinome-wide off-target (305 kinases)	Negative except for p38αMAPK (see ref (14))
Functional GPCR agonist and antagonist (166 GPCRs)	Negative (see ref (14))
Panlabs and others (44 targets)	Negative (see Experimental Section)
	Enzymes: MAO A/B, acetyl cholinesterase, COX-1, COX-2, PDE3A, PDE4D2
	Receptors: Adenosine A_2A, adrenergic (α_1A, α_2A, β₁, β₂), androgen, cannabinoid (CB₁, CB₂), GABA_A, dopamine (D₁, D_2S), cholecystokinin CCK₁, glucocorticoid, histamine (H₁, H₂), muscarinic (M₁, M₂, M₃), NMDA, α4β2 nicotinic acetylcholine, opiate (OP1, OP2, OP3), serotonin (5-HT_1A, 5- HT_1B, 5-HT_2A, 5-HT_2B, 5-HT₃), vasopression V_1A
	Channels: L-type calcium channel, potassium channel ([K_A], hERG), sodium channel
	Transporters: Dopamine, norepinephrine, Serotonin
Liver microsome stability	Human, T_1/2 > 60 min; rat, T_1/2 > 40 min (see ref (14))
Hepatocyte stability	Human, T_1/2 > 120 min; dog, T_1/2 > 120 min (see ref (14))
CYP inhibition: (1A2, 2B6, 2D6, 2C8, 2C9, 2C19, 3A4)	Negative (see ref (14))
CYP substrate: (1A2, 2B6, 2D6, 2C8, 2C9, 2C19, 3A4)	Negative (see ref (14))
CYP induction	Negative (see Experimental Section)
Permeability, pump substrate status:
P-gp/Caco-2	Not substrate/highly permeable (see ref (14))
BCRP/MDCK	Not substrate/highly permeable (see ref (14))
Dose range finding: 14-day daily oral with TK (rat)	NOAEL^a = 125 mg/kg; HED^a = 20.0 mg/kg (see ref (14))
Aged AD KI mouse, oral, single administration: behavior and pathology	NOAEL^a ≥ 250 mg/kg; HED^a = 20.0 mg/kg (see ref (14))

NOAEL= no observable adverse effect level; HED = human equivalent dose.