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MedKoo Cat#: 529210 | Name: Odevixibat
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Description:

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

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. Odevixibat was approved in 2021 to treat pruritus.

Chemical Structure

Odevixibat
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
5mg USD 250.00 Ready to ship
10mg USD 450.00 2 Weeks
25mg USD 950.00 2 Weeks
50mg USD 1,650.00 2 Weeks
100mg USD 2,950.00 2 Weeks
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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
More Info
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/
Solvent mg/mL mM
Solubility
DMSO 250.0 337.41
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 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.
1: Komaniecka N, Maroszek S, Drozdzik M, Oswald S, Drozdzik M. Transporter Proteins as Therapeutic Drug Targets-With a Focus on SGLT2 Inhibitors. Int J Mol Sci. 2024 Jun 25;25(13):6926. doi: 10.3390/ijms25136926. PMID: 39000033; PMCID: PMC11241231. 2: Odevixibat (Bylvay): CADTH Reimbursement Review: Therapeutic area: Progressive familial intrahepatic cholestasis [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2024 May. Report No.: SR0788CL. PMID: 38985903. 3: Ovchinsky N, Aumar M, Baker A, Baumann U, Bufler P, Cananzi M, Czubkowski P, Durmaz Ö, Fischer R, Indolfi G, Karnsakul WW, Lacaille F, Lee WS, Maggiore G, Rosenthal P, Ruiz M, Sokal E, Sturm E, van der Woerd W, Verkade HJ, Wehrman A, Clemson C, Yu Q, Ni Q, Ruvido J, Manganaro S, Mattsson JP. Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSERT): a phase 3, double- blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2024 Jul;9(7):632-645. doi: 10.1016/S2468-1253(24)00074-8. Epub 2024 Apr 23. PMID: 38670135. 4: Flattmann FE, Mohiuddin FS, Singh A, Tandon A, Lockett SJ, Hirsch JD, Mosieri CN, Kaye AM, Varrassi G, Ahmadzadeh S, Shekoohi S, Kaye AD. Odevixibat: A Novel Bile Salt Inhibitor Treatment for Pruritus in Progressive Familial Intrahepatic Cholestasis. Cureus. 2024 Mar 25;16(3):e56886. doi: 10.7759/cureus.56886. PMID: 38659510; PMCID: PMC11042757. 5: Hof WFJ, de Boer JF, Verkade HJ. Emerging drugs for the treatment of progressive familial intrahepatic cholestasis: a focus on phase II and III trials. Expert Opin Emerg Drugs. 2024 Jul 4:1-16. doi: 10.1080/14728214.2024.2336986. Epub ahead of print. PMID: 38571480. 6: Odevixibat (Bylvay): CADTH Reimbursement Recommendation: Indication: The treatment of pruritus in patients aged 6 months or older with progressive familial intrahepatic cholestasis [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2024 Mar. Report No.: SR0788. PMID: 38648297. 7: Herta T, Dröge C, Herber A, Keitel V, Berg T. Odevixibat treatment in an adult patient with advanced icteric progressive cholestatic liver disease. JHEP Rep. 2023 Dec 12;6(3):100978. doi: 10.1016/j.jhepr.2023.100978. PMID: 38375459; PMCID: PMC10875579. 8: Spinner NB, Loomes KM, Krantz ID, Gilbert MA. Alagille Syndrome. 2000 May 19 [updated 2024 Jan 4]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301450. 9: Jeyaraj R, Maher ER, Kelly D. Paediatric research sets new standards for therapy in paediatric and adult cholestasis. Lancet Child Adolesc Health. 2024 Jan;8(1):75-84. doi: 10.1016/S2352-4642(23)00259-6. Epub 2023 Nov 22. PMID: 38006895. 10: De Bruijn VMP, Te Kronnie W, Rietjens IMCM, Bouwmeester H. Intestinal in vitro transport assay combined with physiologically based kinetic modeling as a tool to predict bile acid levels in vivo. ALTEX. 2024 Jan 9;41(1):20-36. doi: 10.14573/altex.2302011. Epub 2023 Jul 27. PMID: 37528756. 11: Di Giorgio A, Sciveres M, Fuoti M, Sonzogni A, Mandato C, D'Antiga L. Treatment with an ileal bile acid transporter inhibitor in patients with TJP2 deficiency. Clin Res Hepatol Gastroenterol. 2023 Oct;47(8):102185. doi: 10.1016/j.clinre.2023.102185. Epub 2023 Jul 26. PMID: 37499899. 12: Thompson RJ, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Di Giorgio A, Durmaz Ö, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Lacaille F, Lachaux A, Lainka E, Loomes KM, Mack CL, Mattsson JP, McKiernan P, Ni Q, Özen H, Rajwal SR, Roquelaure B, Shteyer E, Sokal E, Sokol RJ, Soufi N, Sturm E, Tessier ME, van der Woerd WL, Verkade HJ, Vittorio JM, Wallefors T, Warholic N, Yu Q, Horn P, Kjems L. Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis. JHEP Rep. 2023 Apr 29;5(8):100782. doi: 10.1016/j.jhepr.2023.100782. PMID: 37456676; PMCID: PMC10338319. 13: Hüpper MN, Pichler J, Huber WD, Heilos A, Schaup R, Metzelder M, Langer S. Surgical versus Medical Management of Progressive Familial Intrahepatic Cholestasis-Case Compilation and Review of the Literature. Children (Basel). 2023 May 26;10(6):949. doi: 10.3390/children10060949. PMID: 37371180; PMCID: PMC10297335. 14: Ganschow R, Maucksch C. Odevixibat Treatment of Alagille Syndrome: A Case Report. JPGN Rep. 2023 Mar 24;4(2):e301. doi: 10.1097/PG9.0000000000000301. PMID: 37200711; PMCID: PMC10187842. 15: Nomden M, Kuipers F, Hulscher JBF, Lindström E, Valcheva V, Verkade HJ. Odevixibat Treatment Induces Biliary Bile Acid Secretion in Responsive Patients With Bile Salt Export Pump Deficiency. Gastroenterology. 2023 Aug;165(2):496-498.e1. doi: 10.1053/j.gastro.2023.03.226. Epub 2023 Mar 31. PMID: 37003564. 16: Porwal M, Kumar A, Rastogi V, Maheshwari KK, Verma A. Odevixibat: A Review of a Bioactive Compound for the Treatment of Pruritus Approved by the FDA. Curr Drug Res Rev. 2023 Mar 8. doi: 10.2174/2589977515666230308125238. Epub ahead of print. PMID: 36892028. 17: Levien TL, Baker DE. Formulary Drug Review: Odevixibat. Hosp Pharm. 2023 Apr;58(2):125-133. doi: 10.1177/00185787211069036. Epub 2022 Feb 8. PMID: 36890950; PMCID: PMC9986570. 18: Pepe A, Colucci A, Carucci M, Nazzaro L, Bucci C, Ranucci G, Di Giorgio A, Vajro P, Mandato C. Case Report: Add-on treatment with odevixibat in a new subtype of progressive familial intrahepatic cholestasis broadens the therapeutic horizon of genetic cholestasis. Front Pediatr. 2023 Feb 14;11:1061535. doi: 10.3389/fped.2023.1061535. PMID: 36865697; PMCID: PMC9974160. 19: Muntaha HST, Munir M, Sajid SH, Sarfraz Z, Sarfraz A, Robles-Velasco K, Sarfraz M, Felix M, Cherrez-Ojeda I. Ileal Bile Acid Transporter Blockers for Cholestatic Liver Disease in Pediatric Patients with Alagille Syndrome: A Systematic Review and Meta-Analysis. J Clin Med. 2022 Dec 19;11(24):7526. doi: 10.3390/jcm11247526. PMID: 36556142; PMCID: PMC9784790. 20: Laue T, Baumann U. Odevixibat: an investigational inhibitor of the ileal bile acid transporter (IBAT) for the treatment of biliary atresia. Expert Opin Investig Drugs. 2022 Nov;31(11):1143-1150. doi: 10.1080/13543784.2022.2151890. Epub 2022 Dec 14. PMID: 36440482.