GST-HG131

• CAT Number: I042660
• CAS Number: 2270215-69-3
• Molecular Formula: C23H29NO7
• Molecular Weight: 431.48
• Purity: ≥95%
• Synonyms: (7R)-7-tert-butyl-2-methoxy-3-(3-methoxypropoxy)-11-oxo-6,7-dihydropyrido[1,2-d][1,4]benzoxazepine-10-carboxylic acid
• InChI: InChI=1S/C23H29NO7/c1-23(2,3)21-13-31-18-11-20(30-8-6-7-28-4)19(29-5)9-14(18)16-10-17(25)15(22(26)27)12-24(16)21/h9-12,21H,6-8,13H2,1-5H3,(H,26,27)/t21-/m0/s1
• InChIKey: PQMAMDUBYCMNAT-NRFANRHFSA-N
• SMILES: CC(C)(C)C1COC2=CC(=C(C=C2C3=CC(=O)C(=CN13)C(=O)O)OC)OCCCOC

GST-HG131 is a specific inbihitor of hepatitis B virus (HBV) surface antigen, belongs to dihydrobenzopyridooxazepine (DBP) series. GST-HG131 exhibits excellent and specific HBV antigens inhibition with EC50 of 28.2 nM (HBsAg) and 16.0 nM (HBeAg), respectively, but also it is safety for animal[1].
GST-HG131 shows moderate permeability in Caco-2 assay, low rat and human plasma protein binding, low clearance in liver microsomal stability assays[1].
GST-HG131 shows antiviral activity in primary human hepatocytes (PHH) expressing HBV, inhibits HBV antigens (both HBsAg and HBeAg)[1].
GST-HG131 (500 nM) appears to inhibit HBV antigens through inhibition of HBV RNAs in a dose- and time-dependent manner[1].
GST-HG131 shows specific HBV inhibition over other viruses, such as hepatitis C virus, herpes simplex virus type 1 and influenza virus H1N1[1].
GST-HG131 exhibits low clearance, moderate plasma half-life (T1/2), high plasma exposure (Cmax and AUC) and oral bioavailability[1].
GST-HG131 (3, 10, and 30 mg/kg; i.v., tail vein injection; once daily for 4 weeks) shows HBV inhibition in an AAV/HBV mouse model[1].
GST-HG131 (100, 300, and 1000 mg/kg; p.o.; once daily for 14 d) is well tolerated at 300 mg/kg and 100 mg/kg in rat preliminary toxicology study[1].
PK parameter in mouse, rat, and dog[1]
Note: Male C57BL/6 mice (iv/po: 0.5 mg/kg), male SD rats (iv/po: 0.5 mg/kg) and Beagle dogs (iv/po: 0.33 mg/kg).

Parameter
CL(iv) (mL/min/kg)
Vdss(iv) (L/kg)
T1/2 (h)
Cmax(po) (nM)
AUC0-last(po) (nM·h)
Bioavailability (F%)

Mouse
75
5.8
2.5
1055
876
91.6

Rat
28
1.72
2.0
659
1832
71.1

Dog
4.04
1.08
3.39
4850
26500
93.2

Reference

[1]. Hu Y, et al. Discovery and preclinical evaluations of GST-HG131, a novel HBV antigen inhibitor for the treatment of chronic hepatitis B infection. Bioorg Med Chem Lett. 2022 Nov 1;75:128977.
 [Content Brief]