SSTR5 antagonist 1

SSTR5 antagonist 1 (compound 25a) is a selective and orally available somatostatin receptor subtype 5 (SSTR5) antagonist with IC₅₀s of 9.6 and 57 nM for hSSTR5 and mSSTR5, respectively^[1]. IC50 & Target:IC50: 9.6 nM (hSSTR5), 57 nM (mSSTR5)^[1] In Vitro:SSTR5 antagonist 1 (compound 25a) (30 μM) inhibits hERG activity by 5.6%^[1].
SSTR5 antagonist 1 (10 μM) shows highly selective inhibitory effect on SSTR5 over SSTR1-4, with inhibition rates of 11%, 8%, 14%, 10%^[1].
SSTR5 antagonist 1 (1 μM; 15 min and 30 min) exhibits good metabolic stability toward both human and mouse microsomes with in vitro CLint value of <10 μL/min/kg (HLM) and 19 μL/min/kg (MLM), respectively^[1].
In Vivo:SSTR5 antagonist 1 (compound 25a) (1 mg/kg; p.o.; single dose) is orally available with acceptable plasma exposure in mice in pharmacokinetic screening and exhibits excellent solubility (260 μg/mL, pH=6.8)^[1].
SSTR5 antagonist 1 (100 mg/kg; p.o.; single dose; measured at 0-120 min) augments insulin secretion in a glucose-dependent manner and lowers blood glucose concentration in high-fat diet fed C57BL/6J mice^[1].
SSTR5 antagonist 1 (1, 3, 10, and 30 mg/kg; p.o.; single dose) shows dose-dependent effect on glucose excursion measured during the oral glucose tolerance test in HFD fed C57BL/6J mice^[1].
Pharmacokinetic profiles in male ICR mouse (8-week-old)^[1]

Route	Dose (mg/kg)	CLtotal (mL/h/kg)	Vss (mL/kg)	MRT (h)
iv	0.1	1761	3052	1.7	/
Route	Dose (mg/kg)	Cmax (ng/mL)	Tmax (h)	AUC0-8 h (ng·h/mL)	F (%)
po	1	74.8	2.0	332	58