Odevixibat
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 529210

CAS#: 501692-44-0 (free base)

Description: Odevixibat, also known as AZD 8294, is a potent, once-daily, non-systemic ileal bile acid transport inhibitor (IBATi). Odevixibat is being developed to treat rare pediatric cholestatic liver diseases, including progressive familial intrahepatic cholestasis (PFIC), biliary atresia and Alagille syndrome. Odevixibat acts locally in the small intestine. A4250 is well tolerated. By blocking ileal bile acid transporter in the terminal ileum, it highly efficiently interrupts the enterohepatic circulation of BAs, and should be of benefit to patients with cholestatic liver diseases. Odevixibat was approved in 2021 to treat pruritus.


Chemical Structure

img
Odevixibat
CAS# 501692-44-0 (free base)

Theoretical Analysis

MedKoo Cat#: 529210
Name: Odevixibat
CAS#: 501692-44-0 (free base)
Chemical Formula: C37H48N4O8S2
Exact Mass: 740.2914
Molecular Weight: 740.93
Elemental Analysis: C, 59.98; H, 6.53; N, 7.56; O, 17.27; S, 8.65

Price and Availability

Size Price Availability Quantity
1.0mg USD 90.0 Ready to ship
5.0mg USD 175.0 Ready to ship
10.0mg USD 295.0 2 Weeks
25.0mg USD 650.0 2 Weeks
50.0mg USD 1150.0 2 Weeks
Bulk inquiry

Related CAS #: 501692-44-0 (free base)   2409081-01-0 (hydrate)   Odevixibat HCl  

Synonym: AZD 8294; AZD8294; AZD-8294; A-4250; A4250; A 4250; AR-H 064974; AR-H064974; AR-H-064974; Odevixibat

IUPAC/Chemical Name: (S)-2-((R)-2-(2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[f][1,2,5]thiadiazepin-8-yl)oxy)acetamido)-2-(4-hydroxyphenyl)acetamido)butanoic acid

InChi Key: XULSCZPZVQIMFM-IPZQJPLYSA-N

InChi Code: 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

SMILES Code: CC[C@H](NC([C@H](NC(COC1=C(SC)C=C(C2=C1)N(C3=CC=CC=C3)CC(CCCC)(CCCC)NS2(=O)=O)=O)C4=CC=C(O)C=C4)=O)C(O)=O

Appearance: Solid powder

Purity: >97% (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: >2 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: Odevixibat (A4250) is a potent and selective inhibitor of the ileal bile acid transporter (IBAT).
In vitro activity: TBD
In vivo activity: Eight week old Mdr2(-/-) (Abcb4(-/-)) mice (model of cholestatic liver injury and sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) - a highly potent and selective ASBT inhibitor - or a chow diet. A4250 improved sclerosing cholangitis in Mdr2(-/-) mice and significantly reduced serum alanine aminotransferase, alkaline phosphatase and BAs levels, hepatic expression of pro-inflammatory (Tnf-α, Vcam1, Mcp-1) and pro-fibrogenic (Col1a1, Col1a2) genes and bile duct proliferation (mRNA and immunohistochemistry for cytokeratin 19 (CK19)). Furthermore, A4250 significantly reduced bile flow and biliary BA output, which correlated with reduced Bsep transcription, while Ntcp and Cyp7a1 were induced. Importantly A4250 significantly reduced biliary BA secretion but preserved HCO3(-) and biliary phospholipid secretion resulting in an increased HCO3(-)/BA and PL/BA ratio. In addition, A4250 profoundly increased fecal BA excretion without causing diarrhea and altered BA pool composition, resulting in diminished concentrations of primary BAs tauro-β-muricholic acid and taurocholic acid. In conclusion, pharmacological ASBT inhibition attenuates cholestatic liver and bile duct injury by reducing biliary BA concentrations in mice. Reference: J Hepatol. 2016 Mar;64(3):674-81.https://pubmed.ncbi.nlm.nih.gov/26529078/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 250.0 337.41

Preparing Stock Solutions

The following data is based on the product molecular weight 740.93 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.

Recalculate based on batch purity %
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. Baghdasaryan A, Fuchs CD, Österreicher CH, Lemberger UJ, Halilbasic E, Påhlman I, Graffner H, Krones E, Fickert P, Wahlström A, Ståhlman M, Paumgartner G, Marschall HU, Trauner M. Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis. J Hepatol. 2016 Mar;64(3):674-81. doi: 10.1016/j.jhep.2015.10.024. Epub 2015 Oct 31. PMID: 26529078.
In vitro protocol: TBD
In vivo protocol: 1. Baghdasaryan A, Fuchs CD, Österreicher CH, Lemberger UJ, Halilbasic E, Påhlman I, Graffner H, Krones E, Fickert P, Wahlström A, Ståhlman M, Paumgartner G, Marschall HU, Trauner M. Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis. J Hepatol. 2016 Mar;64(3):674-81. doi: 10.1016/j.jhep.2015.10.024. Epub 2015 Oct 31. PMID: 26529078.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Saveleva EE, Tyutrina ES, Nakanishi T, Tamai I, Salmina AB. Ingibitory natriĭ-zavisimogo perenoschika zhelchnykh kislot (ASBT) kak perspektivnye lekarstvennye sredstva [The inhibitors of the apical sodium-dependent bile acid transporter (ASBT) as promising drugs]. Biomed Khim. 2020 May;66(3):185-195. Russian. doi: 10.18097/PBMC20206603185. PMID: 32588824.

2: Al-Dury S, Wahlström A, Wahlin S, Langedijk J, Elferink RO, Ståhlman M, Marschall HU. Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis. Sci Rep. 2018 Apr 27;8(1):6658. doi: 10.1038/s41598-018-25214-0. PMID: 29704003; PMCID: PMC5923243.

3: Baghdasaryan A, Fuchs CD, Österreicher CH, Lemberger UJ, Halilbasic E, Påhlman I, Graffner H, Krones E, Fickert P, Wahlström A, Ståhlman M, Paumgartner G, Marschall HU, Trauner M. Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis. J Hepatol. 2016 Mar;64(3):674-81. doi: 10.1016/j.jhep.2015.10.024. Epub 2015 Oct 31. PMID: 26529078.

4: Graffner H, Gillberg PG, Rikner L, Marschall HU. The ileal bile acid transporter inhibitor A4250 decreases serum bile acids by interrupting the enterohepatic circulation. Aliment Pharmacol Ther. 2016 Jan;43(2):303-10. doi: 10.1111/apt.13457. Epub 2015 Nov 2. PMID: 26527417.