9-(N-methyl-L-isoleucine)-cyclosporin A

Cyclic Nonribosomal Peptide / Cyclosporin AnalogueRx: ResearchCompound: Research

Also known as: MeIle4-cyclosporin, N-methyl-4-isoleucine cyclosporin, NIM811, SDZ NIM 811

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Summary

9-(N-methyl-L-isoleucine)-cyclosporin A (also known as NIM811) is a non-immunosuppressive cyclosporin A analogue developed primarily as an antiviral agent against hepatitis C virus. The substitution at position 9 eliminates calcineurin inhibition while retaining high-affinity cyclophilin binding, making it a prototype for cyclophilin inhibitor-based antiviral therapy. It has also been investigated for cytoprotective properties related to mitochondrial permeability transition pore (mPTP) inhibition.

Mechanism of Action

Inhibits cyclophilin B (CypB) and blocks hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase interaction with cyclophilins, thereby suppressing HCV replication without significant calcineurin inhibition; lacks the immunosuppressive activity of cyclosporin A.

Routes of Administration

IntravenousOral

Goals & Uses

  • HIV-1 replication inhibitionAntiviralLow
  • Cytoprotection via mPTP inhibitionCardioprotection / HepatoprotectionLow
  • Hepatitis C virus (HCV) suppressionAntiviralModerate

Contraindications

  • Hypersensitivity to cyclosporin or cyclosporin analoguesAllergyHigh
  • Severe hepatic impairmentOrganModerateLiver function concerns

Adverse Effects

  • HeadacheNeurologicUncommonPain in the head or upper neck
  • Gastrointestinal disturbanceGastrointestinalCommon
  • Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers
  • NephrotoxicityRenalRare

Drug Interactions

  • P-glycoprotein substrates/inhibitorsLow
  • CYP3A4 inducers (e.g., rifampicin, carbamazepine)Moderate
  • CYP3A4 inhibitors (e.g., ketoconazole, ritonavir)Moderate

Population Constraints

  • PregnancyReproductive SafetyRelative
  • Renal impairmentOrgan ImpairmentRelative
  • Pediatric populationAgeRelative

Regulatory Status

  • European UnionUnapprovedNo marketing authorization; investigated as research compound.
  • United StatesUnapprovedInvestigated in Phase I/II trials for HCV; not submitted for NDA approval; development discontinued.

NIM811 has not received regulatory approval in any jurisdiction. It was investigated in early-phase clinical trials for chronic hepatitis C but development was discontinued. Remains a research tool compound.

Evidence & Sources

No sources recorded yet.

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