(11S,14S)-Cyclo-(L-Trp-L-Phe), also known as **cyclosporin A**, is a cyclic undecapeptide produced by the fungus *Tolypocladium inflatum*. It's a potent immunosuppressant drug with a complex structure and an intriguing history.
**Structure:**
- It consists of 11 amino acids arranged in a cyclic structure.
- The sequence is: (L-MeBmt)-L-Abu-L-Sar-L-MeLeu-L-Val-L-MeLeu-L-Ala-L-D-Ala-L-Thr-L-Phe-L-Trp
- The presence of N-methylated amino acids (MeBmt, MeLeu, Sar), an unusual D-alanine residue, and the cyclic nature are key to its biological activity.
**Importance in Research:**
1. **Immunosuppression:**
- Cyclosporin A is a powerful immunosuppressant used to prevent organ rejection after transplantation.
- It works by inhibiting the production of interleukin-2, a cytokine crucial for T cell activation and proliferation.
- It's also used to treat autoimmune diseases like rheumatoid arthritis and psoriasis.
2. **Understanding Immunosuppression:**
- Studying cyclosporin A has been instrumental in deciphering the intricate pathways involved in immune regulation.
- It provided a model for understanding the role of calcineurin, a phosphatase involved in T cell activation, and its interaction with cyclosporin A.
3. **Drug Development:**
- Cyclosporin A inspired the development of other immunosuppressants like tacrolimus and sirolimus.
- Its unique structure and activity have spurred research into new drug candidates for a variety of conditions, including cancer and neurodegenerative disorders.
4. **Applications in Agriculture:**
- Cyclosporin A has shown potential as an antifungal agent in agriculture.
- It's being studied as a potential alternative to synthetic pesticides.
5. **Bioavailability Studies:**
- Cyclosporin A's complex structure presents challenges in terms of bioavailability and drug delivery.
- Research is ongoing to improve its oral absorption and reduce its side effects.
**Overall, (11S,14S)-Cyclo-(L-Trp-L-Phe) or cyclosporin A is a crucial molecule with significant implications in medicine, agriculture, and research. Its complex structure, powerful immunosuppressive properties, and potential for further development make it a fascinating area of study.**
| ID Source | ID |
|---|---|
| PubMed CID | 7408486 |
| CHEMBL ID | 190059 |
| CHEBI ID | 68230 |
| Synonym |
|---|
| MLS002704309 |
| smr001571011 |
| chebi:68230 , |
| CHEMBL190059 |
| (3s,6s)-3-benzyl-6-(1h-indol-3-ylmethyl)piperazine-2,5-dione |
| (11s,14s)-cyclo-(l-trp-l-phe) |
| cyclo(-phe-trp) |
| 6521-48-8 |
| mfcd00237619 |
| Q27136723 |
| isorugulosuvine |
| DTXSID901017851 |
| C22142 |
| cyclo(l-trp-l-phe) |
| HY-P5051 |
| CS-0675894 |
| (3s,6s)-3-((1h-indol-3-yl)methyl)-6-benzylpiperazine-2,5-dione |
| Role | Description |
|---|---|
| Aspergillus metabolite | Any fungal metabolite produced during a metabolic reaction in the mould, Aspergillus. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| indoles | Any compound containing an indole skeleton. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| chromobox protein homolog 1 | Homo sapiens (human) | Potency | 70.7946 | 0.0060 | 26.1688 | 89.1251 | AID540317 |
| TAR DNA-binding protein 43 | Homo sapiens (human) | Potency | 6.3096 | 1.7783 | 16.2081 | 35.4813 | AID652104 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| RNA polymerase II cis-regulatory region sequence-specific DNA binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| DNA binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| double-stranded DNA binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| RNA binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| mRNA 3'-UTR binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| protein binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| lipid binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| identical protein binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| pre-mRNA intronic binding | TAR DNA-binding protein 43 | Homo sapiens (human) |
| molecular condensate scaffold activity | TAR DNA-binding protein 43 | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| intracellular non-membrane-bounded organelle | TAR DNA-binding protein 43 | Homo sapiens (human) |
| nucleus | TAR DNA-binding protein 43 | Homo sapiens (human) |
| nucleoplasm | TAR DNA-binding protein 43 | Homo sapiens (human) |
| perichromatin fibrils | TAR DNA-binding protein 43 | Homo sapiens (human) |
| mitochondrion | TAR DNA-binding protein 43 | Homo sapiens (human) |
| cytoplasmic stress granule | TAR DNA-binding protein 43 | Homo sapiens (human) |
| nuclear speck | TAR DNA-binding protein 43 | Homo sapiens (human) |
| interchromatin granule | TAR DNA-binding protein 43 | Homo sapiens (human) |
| nucleoplasm | TAR DNA-binding protein 43 | Homo sapiens (human) |
| chromatin | TAR DNA-binding protein 43 | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID1347086 | qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal | 2020 | Antiviral research, 01, Volume: 173 | A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity. |
| AID651635 | Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression | |||
| AID1745845 | Primary qHTS for Inhibitors of ATXN expression | |||
| AID1347083 | qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen | 2020 | Antiviral research, 01, Volume: 173 | A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity. |
| AID1347082 | qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal | 2020 | Antiviral research, 01, Volume: 173 | A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity. |
| AID661416 | Cytotoxicity against human K562 cells after 72 hrs by MTT assay | 2012 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 22, Issue:12 | Prenylation at the indole ring leads to a significant increase of cytotoxicity of tryptophan-containing cyclic dipeptides. |
| AID661418 | Cytotoxicity against human cisplatin resistant A2780 cells after 72 hrs by MTT assay | 2012 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 22, Issue:12 | Prenylation at the indole ring leads to a significant increase of cytotoxicity of tryptophan-containing cyclic dipeptides. |
| AID611588 | Antioxidant activity assessed as DPPH radical scavenging activity after 30 mins by spectrophotometry | 2011 | Journal of natural products, Jul-22, Volume: 74, Issue:7 | Sesquiterpene and xanthone derivatives from the sea fan-derived fungus Aspergillus sydowii PSU-F154. |
| AID243879 | Percent inhibition of human calpain 1 at 100 uM; Inhibition within 110% | 2005 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 15, Issue:12 | Synthesis of a small library of diketopiperazines as potential inhibitors of calpain. |
| AID661417 | Cytotoxicity against human cisplatin sensitive A2780 cells after 72 hrs by MTT assay | 2012 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 22, Issue:12 | Prenylation at the indole ring leads to a significant increase of cytotoxicity of tryptophan-containing cyclic dipeptides. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 2 (25.00) | 29.6817 |
| 2010's | 4 (50.00) | 24.3611 |
| 2020's | 2 (25.00) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.
| This Compound (12.25) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 8 (100.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||