Bulevirtide

Last updated

Bulevirtide
Bulevirtide.svg
Clinical data
Trade names Hepcludex
Other namesMyrB, Myrcludex-B [1]
Pregnancy
category
Routes of
administration 		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C248H355N65O72
Molar mass 5398.951 g·mol−1
3D model (JSmol)
  • 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
  • InChI=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
  • Key:WQNDXLHKAMIGEX-WOAPPVHJSA-N

Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication used for the treatment of chronic hepatitis D (in the presence of hepatitis B). [8]

Contents

The most common side effects include raised levels of bile salts in the blood and reactions at the site of injection. [8]

Bulevirtide works by attaching to and blocking a receptor (target) through which the hepatitis delta and hepatitis B viruses enter liver cells. [8] 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. [8]

Bulevirtide was approved for medical use in the European Union in July 2020, [8] and in Canada in August 2025. [5]

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. [8] [10]

Pharmacology

Mechanism of action

Bulevirtide binds and inactivates the sodium/bile acid cotransporter, blocking both hepatitis B and hepatitis D viruses from entering hepatocytes. [11]

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 [12] [13] that can also dock to NTCP, blocking the virus's entry mechanism. [14]

Bulevirtide is also effective against hepatitis D because the hepatitis D virus uses the same entry receptor as the hepatitis B virus and is only effective in the presence of a hepatitis B virus infection. [14]

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. [15] 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. [16]

Structural formula

Bulevirtide is a 47-amino acid peptide with the following sequence: [17]

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)

References

  1. ↑ Deterding K, Wedemeyer H (2019). "Beyond Pegylated Interferon-Alpha: New Treatments for Hepatitis Delta". AIDS Reviews. 21 (3): 126–134. doi:10.24875/AIDSRev.19000080. PMID   31532397. S2CID   202674681.
  2. 1 2 "Hepcludex (bulevirtide acetate)". Therapeutic Goods Administration (TGA). 12 August 2024. Retrieved 12 October 2024.
  3. ↑ "Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024". Federal Register of Legislation. 30 May 2024. Retrieved 10 June 2024.
  4. ↑ "Hepcludex (Gilead Sciences Pty Ltd)". Therapeutic Goods Administration (TGA). 13 September 2024. Retrieved 15 September 2024.
  5. 1 2 "Hepcludex Product information". Health Canada . 8 August 2025. Retrieved 20 August 2025.
  6. ↑ "Summary Basis of Decision for Hepcludex". Drug and Health Products Portal. 29 September 2025. Retrieved 12 October 2025.
  7. ↑ "Hepcludex 2 mg powder for solution for injection - Summary of Product Characteristics (SmPC)". (emc). 30 March 2022. Retrieved 1 July 2022.
  8. 1 2 3 4 5 6 7 "Hepcludex EPAR". European Medicines Agency (EMA). 26 May 2020. Retrieved 12 August 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. ↑ "Hepcludex Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  10. ↑ "Summary of opinion: Hepcludex" (PDF). European Medicines Agency (EMA). 28 May 2020.
  11. ↑ Francisco EM (29 May 2020). "Hepcludex". European Medicines Agency (EMA). Archived from the original on 15 June 2020. Retrieved 6 August 2020.
  12. ↑ Volz T, Allweiss L, Ben MBarek M, Warlich M, Lohse AW, Pollok JM, et al. (May 2013). "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. doi:10.1016/j.jhep.2012.12.008. PMID   23246506.
  13. ↑ Abbas Z, Abbas M (August 2015). "Management of hepatitis delta: Need for novel therapeutic options". World Journal of Gastroenterology. 21 (32): 9461–9465. doi: 10.3748/wjg.v21.i32.9461 . PMC   4548107 . PMID   26327754.
  14. 1 2 Spreitzer H (14 September 2015). "Neue Wirkstoffe – Myrcludex B". Österreichische Apothekerzeitung (in German) (19/2015): 12.
  15. ↑ 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
  16. ↑ Roscam Abbing RL, Slijepcevic D, Donkers JM, Havinga R, Duijst S, Paulusma CC, et al. (January 2020). "Blocking Sodium-Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice". Hepatology. 71 (1): 247–258. doi:10.1002/hep.30792. PMC   7003915 . PMID   31136002.
  17. ↑ Sauter M, Blank A, Stoll F, Lutz N, Haefeli WE, Burhenne J (September 2021). "Intact plasma quantification of the large therapeutic lipopeptide bulevirtide". Analytical and Bioanalytical Chemistry. 413 (22): 5645–5654. doi:10.1007/s00216-021-03384-7. PMC   8410713 . PMID   34018034.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.