| Stereochemistry | ABSOLUTE |
| Molecular Formula | C37H48N4O8S2 |
| Molecular Weight | 740.929 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCC1(CCCC)CN(C2=CC=CC=C2)C3=C(C=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C4=CC=C(O)C=C4)C(SC)=C3)S(=O)(=O)N1
InChI
InChIKey=XULSCZPZVQIMFM-IPZQJPLYSA-N
InChI=1S/C37H48N4O8S2/c1-5-8-19-37(20-9-6-2)24-41(26-13-11-10-12-14-26)29-21-31(50-4)30(22-32(29)51(47,48)40-37)49-23-33(43)39-34(25-15-17-27(42)18-16-25)35(44)38-28(7-3)36(45)46/h10-18,21-22,28,34,40,42H,5-9,19-20,23-24H2,1-4H3,(H,38,44)(H,39,43)(H,45,46)/t28-,34+/m0/s1
A-4250 (odevixibat) is a selective inhibitor of the ileal bile acid transporter (IBAT) that acts locally in the gut. Ileum absorbs glyco-and taurine-conjugated forms of the bile salts. IBAT is the first step in absorption at the brush-border membrane. A-4250 works by decreasing the re-absorption of bile acids from the small intestine to the liver, whichreduces the toxic levels of bile acids during the progression of the disease. It exhibits therapeutic intervention by checking the transport of bile acids. Studies show that A-4250 has the potential to decrease the damage in the liver cells and the development of fibrosis/cirrhosis of the liver known to occur in progressive familial intrahepatic cholestasis. A-4250 is a designated orphan drug in the USA for October 2012. A-4250 is a designated orphan drug in the EU for October 2016. A-4250 was awarded PRIME status for PFIC by EMA in October 2016. A-4250 is in phase II clinical trials by Albireo for the treatment of primary biliary cirrhosis (PBC) and cholestatic pruritus. In an open label Phase 2 study in children with cholestatic liver disease and pruritus, odevixibat showed reductions in serum bile acids and pruritus in most patients and exhibited a favorable overall tolerability profile.
Originator
Approval Year
Cmax
AUC
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
PubMed
Patents
Sample Use Guides
The recommended dosage of BYLVAY is 40 mcg/kg once daily in the morning with a meal. If there is no improvement in pruritus after 3 months, the dosage may be increased in 40 mcg/kg increments up to 120 mcg/kg once daily not to exceed a total daily dose of 6 mg.
Route of Administration:
Oral
Odevixibat was found to be highly specific for the ileal (apical) bile acid transporters with IC50 = 0.13, 0.12, and 1.4 nM for the human, mouse, and canine transporters, respectively, whereas the corresponding value for the human liver (basolateral) sodium/bile acid co-transporter was found to be 93 nM. 3.125, 12.5, and 50 μM odevixibat resulted in 21%, 73%, and 84% inhibition of the sodium-stimulated uptake of 0.5 mM 14C-α-aminoisobutyric acid (AIB), respectively. The apparent Km-value for sodium-stimulated AIB-uptake in the HEK293 cells is approximately 280 uM.
ACTIVE MOIETY
SALT/SOLVATE (PARENT)
