SLC6A19-IN-4

SLC6A19-IN-4 is an allosteric-competitive and orally active B 0 AT1 inhibitor. SLC6A19-IN-4 inhibits both human and mouse B 0 AT1 with IC₅₀ values of 513 nM and 295 nM, respectively. SLC6A19-IN-4 exhibits excellent metabolic stability. SLC6A19-IN-4 significantly increases urinary phenylalanine (Phe) excretion and reduces plasma Phe levels through dual inhibition of B 0 AT1 in both the intestine (reducing absorption) and kidney (promoting excretion) in vivo. SLC6A19-IN-4 can be used for phenylketonuria (PKU) and other disorders involving SLC6 -family transporters research ^[1].

In Vivo, SLC6A19-IN-4 (30 mg/kg, p.o., once) reduces intestinal Phe absorption promotes urinary excretion and lowers systemic Phe levels in male Pahenu2 mice carry a homozygous F263^[1].

In Vitro, SLC6A19-IN-4 (1500-4000 nM) increases the Km for d5-Phe without affecting Vmax, indicating competitive inhibition (Km = 0.866, 5.19, 12.1 mM Vmax = 337, 351, 380 μmol/min/mg-protein) in the Jump-In TI platform cells expressing human SLC6A19 and human Collectrin^[1]. SLC6A19-IN-4 revealed Kd = 123.1 nM for mock cell and mB0AT1 and ACE2-expressing cell and Kd = 46.98 nM in mock cell and hB0AT1 and ACE2-expressing cell^[1].

References:
[1]. Takuya Imazu, et al., Structure-guided development of a potent human B0AT1 inhibitor effective in a mouse model of phenylketonuria. bioRxiv. 2025.10.27.684712