Cyclophilin A (CypA) binds to its ligand (domain II of the NS5A HCV protein) and interacts with the HCV replication complex on the membranous web. By blocking the interaction between CypA and NS5A, the cyclophilin inhibitors (alisporivir, NIM811, SCY-635 or sanglifehrins) abrogate HCV replication.

What do Cyclophilins do?

From PDB: 1CWA​. Cyclophilins (CYPs) are a family of proteins named after their ability to bind to ciclosporin (cyclosporin A), an immunosuppressant which is usually used to suppress rejection after internal organ transplants. They are found in all domains of life.

Where is cyclophilin present?

The 18-kDa archetypal cyclophilin CypA is cytosolic and found in all tissues, whereas other cyclophilins, whether they have a CLD alone or in combination with other domains, are found in the endoplasmic reticulum (ER), the mitochondria or the nucleus. The crystal structures of several cyclophilins have been determined.

How does cyclophilin inhibit calcineurin?

Cyclophilin A forms a ternary complex with cyclosporin A and the calcium-calmodulin-activated serine/threonine-specific protein phosphatase calcineurin; formation of this complex prevents calcineurin from regulating cytokine gene transcription.

What does FK506 mean?

Along with cyclophilin, FKBPs belong to the immunophilin family. FKBP12 is notable in humans for binding the immunosuppressant molecule tacrolimus (originally designated FK506), which is used in treating patients after organ transplant and patients suffering from autoimmune disorders.

What is the mechanism of cyclosporine?

Cyclosporine is a potent immunomodulatory agent with an increasing number of clinical applications. Its major mode of action is inhibition of the production of cytokines involved in the regulation of T-cell activation. In particular, cyclosporine inhibits the transcription of interleukin 2.

What is the role of calcineurin?

Calcineurin is a ubiquitous serine/threonine protein phosphatase. It plays many important physiological roles including T-cell activation, cell cycle control, muscle and heart functions, transcription regulation, learning and memory, and apoptosis.

What is the drug tacrolimus?

Tacrolimus is in a class of medications called immunosupressants. It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

What is the mechanism of action of tacrolimus?

Tacrolimus acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription.

What is rapamycin used for?

Rapamycin (Rapamune, Sirolimus) is a macrolide exhibiting potent antitumor and immunosuppressive activity [261,262]. Rapamycin is thus used in clinical settings to prevent rejection in organ transplantation and to treat certain types of cancer.

What should be avoided when taking cyclosporine?

Avoid drinking grapefruit juice or eating grapefruit while taking cyclosporine or cyclosporine (modified). Your doctor may tell you to limit the amount of potassium in your diet.

What is the origin of cyclosporine?

Cyclosporine was found as a natural product of an earth fungus by researchers at the pharmaceutical company Sandoz Laboratories. It is a stable cyclic peptide with powerful immunosuppressive activity affecting especially the T lymphocytes.

Is cyclosporine A chemotherapy?

RATIONALE: Some cancers become resistant to chemotherapy drugs. Combining cyclosporine with chemotherapy may prevent resistance to the drugs and allow the cancer cells to be killed. …

Condition or disease Intervention/treatment Phase
Leukemia Drug: cyclosporine Drug: etoposide Drug: mitoxantrone hydrochloride Phase 2