Alisporivir Explained

Alisporivir (INN), or Debio 025, DEB025, (or UNIL-025) is a cyclophilin inhibitor.[1] Its structure is reminiscent of, and synthesized from ciclosporin.

It inhibits cyclophilin A.[2] Alisporivir is not immunosuppressive.[3]

It is being researched for potential use in the treatment of hepatitis C.[4] [5] [6] [7] [8] [9] [10] It has also been investigated for Duchenne muscular dystrophy[1] and may have therapeutic potential in Alzheimer's disease.[11]

Alisporivir is under development by Debiopharm for Japan and by Novartis for the rest of the world (licence granted by Debiopharm) since February 2010.

Notes and References

  1. Reutenauer J, Dorchies OM, Patthey-Vuadens O, Vuagniaux G, Ruegg UT . Investigation of Debio 025, a cyclophilin inhibitor, in the dystrophic mdx mouse, a model for Duchenne muscular dystrophy . British Journal of Pharmacology . 155 . 4 . 574–584 . October 2008 . 18641676 . 2579666 . 10.1038/bjp.2008.285 .
  2. Gallay PA, Lin K . Profile of alisporivir and its potential in the treatment of hepatitis C . Drug Design, Development and Therapy . 7 . 105–115 . 15 February 2013 . 23440335 . 3578503 . 10.2147/DDDT.S30946 . free .
  3. Ptak RG, Gallay PA, Jochmans D, Halestrap AP, Ruegg UT, Pallansch LA, Bobardt MD, de Béthune MP, Neyts J, De Clercq E, Dumont JM, Scalfaro P, Besseghir K, Wenger RM, Rosenwirth B . 6 . Inhibition of human immunodeficiency virus type 1 replication in human cells by Debio-025, a novel cyclophilin binding agent . Antimicrobial Agents and Chemotherapy . 52 . 4 . 1302–1317 . April 2008 . 18212100 . 2292519 . 10.1128/AAC.01324-07 .
  4. Paeshuyse J, Kaul A, De Clercq E, Rosenwirth B, Dumont JM, Scalfaro P, Bartenschlager R, Neyts J . 6 . The non-immunosuppressive cyclosporin DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro . Hepatology . 43 . 4 . 761–770 . April 2006 . 16557546 . 10.1002/hep.21102 . 45825453 . free .
  5. Coelmont L, Kaptein S, Paeshuyse J, Vliegen I, Dumont JM, Vuagniaux G, Neyts J . Debio 025, a cyclophilin binding molecule, is highly efficient in clearing hepatitis C virus (HCV) replicon-containing cells when used alone or in combination with specifically targeted antiviral therapy for HCV (STAT-C) inhibitors . Antimicrobial Agents and Chemotherapy . 53 . 3 . 967–976 . March 2009 . 19104013 . 2650540 . 10.1128/AAC.00939-08 .
  6. Flisiak R, Horban A, Gallay P, et al. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology. 2008;47(3):817-826. doi:10.1002/hep.22131
  7. Flisiak R, Feinman SV, Jablkowski M, et al. The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naïve hepatitis C patients. Hepatology. 2009;49(5):1460-1468. doi:10.1002/hep.22835
  8. Buti M, Flisiak R, Kao JH, et al. Alisporivir with peginterferon/ribavirin in patients with chronic hepatitis C genotype 1 infection who failed to respond to or relapsed after prior interferon-based therapy: FUNDAMENTAL, a Phase II trial. J Viral Hepat. 2015;22(7):596-606. doi:10.1111/jvh.12360
  9. Pawlotsky JM, Flisiak R, Sarin SK, et al. Alisporivir plus ribavirin, interferon free or in combination with pegylated interferon, for hepatitis C virus genotype 2 or 3 infection. Hepatology. 2015;62(4):1013-1023. doi:10.1002/hep.27960
  10. Zeuzem S, Flisiak R, Vierling JM, et al. Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II). Aliment Pharmacol Ther. 2015;42(7):829-844. doi:10.1111/apt.13342
  11. Web site: USC study reveals potential new treatment target for Alzheimer's disease Keck School of Medicine of USC. 14 June 2021 . 2021-06-16. en-US.

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