4TOT: Crystal structure of rat cyclophilin D in complex with a potent nonimmunosuppressive inhibitor

Nonimmunosuppressive cyclophilin inhibitors have demonstrated efficacy for the treatment of hepatitis C infection (HCV). However, alisporivir, cyclosporin A, and most other cyclosporins are potent inhibitors of OATP1B1, MRP2, MDR1, and other important drug transporters. Reduction of the side chain hydrophobicity of the P4 residue preserves cyclophilin binding and antiviral potency while decreasing transporter inhibition. Representative inhibitor 33 (NIM258) is a less potent transporter inhibitor relative to previously described cyclosporins, retains anti-HCV activity in cell culture, and has an acceptable pharmacokinetic profile in rats and dogs. An X-ray structure of 33 bound to rat cyclophilin D is reported.
PDB ID: 4TOTDownload
MMDB ID: 124709
PDB Deposition Date: 2014/6/6
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 2.39  Å
Source Organism:
Similar Structures:
Biological Unit for 4TOT: dimeric; determined by author and by software (PISA)
Molecular Components in 4TOT
Label Count Molecule
Protein (1 molecule)
Peptidyl-prolyl Cis-trans Isomerase F, Mitochondrial(Gene symbol: Ppif)
Molecule annotation
Nucleotide(1 molecule)
Nonimmunosuppressive Inhibitor
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB