Bulevirtide Explained

Tradename:Hepcludex
Routes Of Administration:Subcutaneous
Atc Prefix:J05
Atc Suffix:AX28
Legal Au:S4
Legal Au Comment:[1]
Legal Uk:POM
Legal Uk Comment:[2]
Legal Eu:Rx-only
Legal Eu Comment:[3]
Index2 Label:as salt
Cas Number:2012558-47-1
Drugbank:DB15248
Unii:WKM56H3TLB
Kegg:D11877
Kegg2:D11878
Chembl:4297711
Synonyms:MyrB, Myrcludex-B[4]
C:248
H:355
N:65
O:72
Smiles:CCCCCCCCCCCCCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)NCC(N)=O)C(C)C)C(C)C)[C@@H](C)O
Stdinchi:1S/C248H355N65O72/c1-16-17-18-19-20-21-22-23-24-25-38-75-193(327)265-118-196(330)304-205(133(15)316)241(378)295-163(104-188(256)322)224(361)283-152(91-127(6)7)216(353)303-175(122-315)232(369)306-204(129(10)11)248(385)313-88-53-74-182(313)239(376)301-172(107-191(259)325)246(383)312-87-50-70-178(312)235(372)291-150(89-125(2)3)209(346)268-120-195(329)274-154(93-135-56-32-27-33-57-135)217(354)296-168(95-137-60-36-29-37-61-137)242(379)308-83-49-72-180(308)237(374)294-167(111-201(339)340)230(367)286-157(98-140-115-261-123-269-140)220(357)277-148(76-78-183(251)317)213(350)282-151(90-126(4)5)215(352)300-173(112-202(341)342)247(384)307-82-47-68-176(307)233(370)273-132(14)208(345)279-153(92-134-54-30-26-31-55-134)210(347)267-119-194(328)271-130(12)206(343)280-160(101-185(253)319)226(363)302-174(121-314)231(368)288-161(102-186(254)320)225(362)299-171(106-190(258)324)245(382)311-86-52-73-181(311)238(375)293-166(110-200(337)338)229(366)285-156(96-138-113-263-144-64-41-39-62-142(138)144)219(356)290-165(109-199(335)336)227(364)284-155(94-136-58-34-28-35-59-136)218(355)298-170(105-189(257)323)244(381)310-85-51-71-179(310)236(373)292-162(103-187(255)321)223(360)275-146(66-43-45-80-249)212(349)289-164(108-198(333)334)228(365)287-158(99-141-116-262-124-270-141)221(358)297-169(97-139-114-264-145-65-42-40-63-143(139)145)243(380)309-84-48-69-177(309)234(371)278-149(77-79-197(331)332)211(348)272-131(13)207(344)281-159(100-184(252)318)222(359)276-147(67-44-46-81-250)214(351)305-203(128(8)9)240(377)266-117-192(260)326/h26-37,39-42,54-65,113-116,123-133,146-182,203-205,263-264,314-316H,16-25,38,43-53,66-112,117-122,249-250H2,1-15H3,(H2,251,317)(H2,252,318)(H2,253,319)(H2,254,320)(H2,255,321)(H2,256,322)(H2,257,323)(H2,258,324)(H2,259,325)(H2,260,326)(H,261,269)(H,262,270)(H,265,327)(H,266,377)(H,267,347)(H,268,346)(H,271,328)(H,272,348)(H,273,370)(H,274,329)(H,275,360)(H,276,359)(H,277,357)(H,278,371)(H,279,345)(H,280,343)(H,281,344)(H,282,350)(H,283,361)(H,284,364)(H,285,366)(H,286,367)(H,287,365)(H,288,368)(H,289,349)(H,290,356)(H,291,372)(H,292,373)(H,293,375)(H,294,374)(H,295,378)(H,296,354)(H,297,358)(H,298,355)(H,299,362)(H,300,352)(H,301,376)(H,302,363)(H,303,353)(H,304,330)(H,305,351)(H,306,369)(H,331,332)(H,333,334)(H,335,336)(H,337,338)(H,339,340)(H,341,342)/t130-,131-,132-,133+,146-,147-,148-,149-,150-,151-,152-,153-,154-,155-,156-,157-,158-,159-,160-,161-,162-,163-,164-,165-,166-,167-,168-,169-,170-,171-,172-,173-,174-,175-,176-,177-,178-,179-,180-,181-,182-,203-,204-,205-/m0/s1
Stdinchikey:WQNDXLHKAMIGEX-WOAPPVHJSA-N

Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication for the treatment of chronic hepatitis D (in the presence of hepatitis B).

The most common side effects include raised levels of bile salts in the blood and reactions at the site of injection.

Bulevirtide works by attaching to and blocking a receptor (target) through which the hepatitis delta and hepatitis B viruses enter liver cells. By blocking the entry of the virus into the cells, it limits the ability of HDV to replicate and its effects in the body, reducing symptoms of the disease.

Bulevirtide was approved for medical use in the European Union in July 2020.

Structural formula

Bulevirtide is a 47-amino acid peptide with the following sequence:[5]

CH3(CH2)12CO-Gly-Thr-Asn-Leu-Ser-Val-Pro-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Gly-Ala-Asn-Ser-Asn-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Asn-Lys-Asp-His-Trp-Pro-Glu-Ala-Asn-Lys-Val-Gly-NH2 (C13H27CO-GTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANKVG-NH2)

Medical uses

Bulevirtide is indicated for the treatment of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease.[6] [7]

Pharmacology

Mechanism of action

Bulevirtide binds and inactivates the sodium/bile acid cotransporter, blocking both HBV and HDV viruses from entering hepatocytes.[8]

The hepatitis B virus uses its surface lipopeptide pre-S1 for docking to mature liver cells via their sodium/bile acid cotransporter (NTCP) and subsequently entering the cells. Myrcludex B is a synthetic N-acylated pre-S1[9] [10] that can also dock to NTCP, blocking the virus's entry mechanism.[11]

The drug is also effective against hepatitis D because the hepatitis D virus uses the same entry receptor as HBV and is only effective in the presence of a hepatitis B virus infection.

Pre-clinical data in mice suggests that pharmacological inhibition of NTCP-mediated bile salt uptake may also be effective to lower hepatic bile salt accumulation in cholestatic conditions. This reduces hepatocellular damage.[12] An increased ratio of phospholipid to bile salts seen in bile upon NTCP inhibition may further contribute to the protective effect as bile salts are less toxic in presence of phospholipids.[13]

Notes and References

  1. Web site: Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024 . Federal Register of Legislation . 30 May 2024 . 10 June 2024.
  2. Web site: Hepcludex 2 mg powder for solution for injection - Summary of Product Characteristics (SmPC) . (emc) . 30 March 2022 . 1 July 2022.
  3. Web site: Hepcludex Product information . Union Register of medicinal products . 3 March 2023.
  4. Deterding K, Wedemeyer H . Beyond Pegylated Interferon-Alpha: New Treatments for Hepatitis Delta . AIDS Reviews . 21 . 3 . 126–134 . 2019 . 31532397 . 10.24875/AIDSRev.19000080 . 202674681 .
  5. Sauter M, Blank A, Stoll F, Lutz N, Haefeli WE, Burhenne J . Intact plasma quantification of the large therapeutic lipopeptide bulevirtide . Analytical and Bioanalytical Chemistry . 413 . 22 . 5645–5654 . September 2021 . 34018034 . 8410713 . 10.1007/s00216-021-03384-7 .
  6. Web site: Hepcludex EPAR . European Medicines Agency (EMA) . 26 May 2020 . 12 August 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. Web site: Summary of opinion: Hepcludex. European Medicines Agency. 28 May 2020.
  8. Web site: Francisco EM . 29 May 2020. Hepcludex. live. https://web.archive.org/web/20200615185201/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/hepcludex . 15 June 2020 . 6 August 2020. European Medicines Agency.
  9. Volz T, Allweiss L, Ben MBarek M, Warlich M, Lohse AW, Pollok JM, Alexandrov A, Urban S, Petersen J, Lütgehetmann M, Dandri M . 6 . The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus . Journal of Hepatology . 58 . 5 . 861–867 . May 2013 . 23246506 . 10.1016/j.jhep.2012.12.008 .
  10. Abbas Z, Abbas M . Management of hepatitis delta: Need for novel therapeutic options . World Journal of Gastroenterology . 21 . 32 . 9461–9465 . August 2015 . 26327754 . 4548107 . 10.3748/wjg.v21.i32.9461 . free .
  11. Spreitzer H . 14 September 2015. Neue Wirkstoffe – Myrcludex B. Österreichische Apothekerzeitung. 19/2015. 12. German.
  12. Na+ -taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice. Slijepcevic D, Roscam Abbing RLP, Fuchs CD, Haazen LCM, Beuers U, Trauner M, Oude Elferink RPJ, van de Graaf SFJ. Hepatology. 2018 Sep;68(3):1057-1069. doi: 10.1002/hep.29888
  13. Roscam Abbing RL, Slijepcevic D, Donkers JM, Havinga R, Duijst S, Paulusma CC, Kuiper J, Kuipers F, Groen AK, Oude Elferink RP, van de Graaf SF . 6 . Blocking Sodium-Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice . Hepatology . 71 . 1 . 247–258 . January 2020 . 31136002 . 7003915 . 10.1002/hep.30792 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Bulevirtide".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.