Synonym
AB-423; AB 423; AB423
IUPAC/Chemical Name
(R)-5-(N-(sec-Butyl)sulfamoyl)-N-(3,4-difluorophenyl)-2-fluorobenzamide
InChi Key
BBLXLHYPDOMJMO-SNVBAGLBSA-N
InChi Code
InChI=1S/C17H17F3N2O3S/c1-3-10(2)22-26(24,25)12-5-7-14(18)13(9-12)17(23)21-11-4-6-15(19)16(20)8-11/h4-10,22H,3H2,1-2H3,(H,21,23)/t10-/m1/s1
SMILES Code
O=C(NC1=CC=C(F)C(F)=C1)C2=CC(S(=O)(N[C@H](C)CC)=O)=CC=C2F
Purity
>95% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
AB-423 is an inhibitor of HBV capsid assembly, and inhibits HBV replication with EC50/EC90 of 0.08-0.27 μM/0.33-1.32 μM in cells.
In vitro activity:
The antiviral activity of AB-423 was evaluated in several different cell culture models of HBV infection. AB-423 showed inhibition of rcDNA production in a concentration-dependent manner. AB-423 showed comparable inhibition of rcDNA production in the HepDE19 cell assay during incubation with AB-423 for 2, 3, 6, or 7 days (data not shown). Consistent with these data, AB-423 also demonstrated inhibition of cccDNA formation-dependent HBeAg production in the HepBHAe82 cell assay with an EC50 of 0.267 μM and inhibited HBV DNA levels in culture supernatants of HepG 2.2.15 cells with an EC50 of 0.134 μM.
Reference: Antimicrob Agents Chemother. 2018 Jun; 62(6): e00082-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971612/
In vivo activity:
A 7-day treatment regimen with AB-423 in this model resulted in a dose-responsive reduction of the serum HBV DNA level of up to 1.4 log10 compared to that in the vehicle-treated control mice (Fig. 7). After 7 days of twice daily oral administration, the preferential accumulation of AB-423 occurred in the liver, the target organ for therapy, with a liver concentration-to-plasma concentration ratio of 11. Examination of other HBV markers in blood and liver showed AB-423 effects consistent with its known mechanism of action. At 100 mg/kg, an HBV DNA reduction of 1.4 log10 in serum correlated with a 0.92-log10 reduction in the liver, the site of drug action where AB-423 inhibits functional capsid particle formation and the production of intact viral particles containing rcDNA. In total, these data demonstrate that oral administration of AB-423 results in anti-HBV activity in vivo and in a manner consistent with its mechanism of action.
Reference: Antimicrob Agents Chemother. 2018 Jun; 62(6): e00082-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971612/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
88.5 |
229.04 |
|
| Ethanol |
77.0 |
199.28 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
386.39
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Mani N, Cole AG, Phelps JR, Ardzinski A, Cobarrubias KD, Cuconati A, Dorsey BD, Evangelista E, Fan K, Guo F, Guo H, Guo JT, Harasym TO, Kadhim S, Kultgen SG, Lee ACH, Li AHL, Long Q, Majeski SA, Mao R, McClintock KD, Reid SP, Rijnbrand R, Snead NM, Micolochick Steuer HM, Stever K, Tang S, Wang X, Zhao Q, Sofia MJ. Preclinical Profile of AB-423, an Inhibitor of Hepatitis B Virus Pregenomic RNA Encapsidation. Antimicrob Agents Chemother. 2018 May 25;62(6):e00082-18. doi: 10.1128/AAC.00082-18. PMID: 29555628; PMCID: PMC5971612.
In vitro protocol:
1. Mani N, Cole AG, Phelps JR, Ardzinski A, Cobarrubias KD, Cuconati A, Dorsey BD, Evangelista E, Fan K, Guo F, Guo H, Guo JT, Harasym TO, Kadhim S, Kultgen SG, Lee ACH, Li AHL, Long Q, Majeski SA, Mao R, McClintock KD, Reid SP, Rijnbrand R, Snead NM, Micolochick Steuer HM, Stever K, Tang S, Wang X, Zhao Q, Sofia MJ. Preclinical Profile of AB-423, an Inhibitor of Hepatitis B Virus Pregenomic RNA Encapsidation. Antimicrob Agents Chemother. 2018 May 25;62(6):e00082-18. doi: 10.1128/AAC.00082-18. PMID: 29555628; PMCID: PMC5971612.
In vivo protocol:
1. Mani N, Cole AG, Phelps JR, Ardzinski A, Cobarrubias KD, Cuconati A, Dorsey BD, Evangelista E, Fan K, Guo F, Guo H, Guo JT, Harasym TO, Kadhim S, Kultgen SG, Lee ACH, Li AHL, Long Q, Majeski SA, Mao R, McClintock KD, Reid SP, Rijnbrand R, Snead NM, Micolochick Steuer HM, Stever K, Tang S, Wang X, Zhao Q, Sofia MJ. Preclinical Profile of AB-423, an Inhibitor of Hepatitis B Virus Pregenomic RNA Encapsidation. Antimicrob Agents Chemother. 2018 May 25;62(6):e00082-18. doi: 10.1128/AAC.00082-18. PMID: 29555628; PMCID: PMC5971612.
1: Mani N, Cole AG, Phelps JR, Ardzinski A, Cobarrubias KD, Cuconati A, Dorsey BD, Evangelista E, Fan K, Guo F, Guo H, Guo JT, Harasym TO, Kadhim S, Kultgen SG, Lee ACH, Li AHL, Long Q, Majeski SA, Mao R, McClintock KD, Reid SP, Rijnbrand R, Snead NM, Micolochick Steuer HM, Stever K, Tang S, Wang X, Zhao Q, Sofia MJ. Preclinical Profile of AB-423, an Inhibitor of Hepatitis B Virus Pregenomic RNA Encapsidation. Antimicrob Agents Chemother. 2018 May 25;62(6). pii: e00082-18. doi: 10.1128/AAC.00082-18. Print 2018 Jun. PubMed PMID: 29555628; PubMed Central PMCID: PMC5971612.
