Rx00075 - Cyclosporine


Name:
Cyclosporine
Rx ID:
Rx00075
Validation Level:
Phenomic Similarity:
0.529
Reference ID:
DB00091
Primary Indications:
Kidney allogeneic transplantation rejection; liver allogeneic transplantation rejection; heart allogeneic transplantation rejection; Rheumatoid Arthritis; psoriasis; adult severe recalcitrant, plaque psoriasis; tear production; ocular inflammation; keratoconjunctivitis sicca; ophthalmic emulsion
Orphan Indications:
Mooren's ulcer; Sjogren's syndrome; allogenic lung transplantation rejection; amyotrophic lateral sclerosis; bone marrow transplantation; bronchiolitis obliterans; cornea transplantation rejection; corneal graft rejection; corneal melting syndromes; graft-versus-host disease; herpes simplex virus stromal keratitis; lung allograft rejection; penetrating keratoplasty; pulmonary rejection events; severe keratoconjunctivitis sicca; vernal keratoconjunctivitis
Rare Indications:
Kidney allogeneic transplantation rejection; liver allogeneic transplantation rejection; heart allogeneic transplantation rejection; chronic rejection
Common Indications:
Severe, active rheumatoid arthritis; Rheumatoid Arthritis; adult severe, recalcitrant, plaque psoriasis
Drug Interactions:
Acetazolamide; Aliskiren; Allopurinol; Amiodarone; Amobarbital; Amphotericin B; Amprenavir; Aprobarbital; Atazanavir; Atorvastatin; ...
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Food Interactions:
Avoid salt substitutes containing potassium. Avoid taking with grapefruit or grapefruit juice as grapefruit can significantly increase serum levels of this product. Red wine may reduce cyclosporine levels due to increased metabolism, therefore it appears prudent to avoid red wine (white wine does not appear to affect cyclosporine metabolism). When taken with a meal, AUC and Cmax of cyclosporine modified decreased.

Interactive 3D Model

Interactive Drug Target Network

Interactive Bipartite Drug Repurposing Graph

Rx00075
Primary Indication
Secondary Indication

Visualize Chemical Properties

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Disease prevalence from Electronic Health Records

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Disease A Disease B A∩B A∩¬B B∩¬A Odds-Ratio P-Value Adjusted P-Value
psoriasis adult severe, recalcitrant, plaque psoriasis 6551 9320 6551 432.932 0 0.0
adult severe recalcitrant, plaque psoriasis adult severe, recalcitrant, plaque psoriasis 6551 6551 6551 615.925 0 0.0
rheumatoid arthritis severe, active rheumatoid arthritis 7378 7378 7378 546.886 0 0.0
kidney allogeneic transplantation rejection liver allogeneic transplantation rejection 252 2697 2098 179.701 0 0.0
liver allogeneic transplantation rejection kidney allogeneic transplantation rejection 252 2098 2697 179.701 0 0.0
keratoconjunctivitis sicca severe keratoconjunctivitis sicca 1599 1599 1599 2523.405 0 0.0
heart allogeneic transplantation rejection kidney allogeneic transplantation rejection 68 592 2697 171.847 1.16E-122 3.74e-119
ocular inflammation rheumatoid arthritis 111 2723 7378 22.293 1.65E-104 5.31e-101

Shared Genetic Architectures of Disease Pairs

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Disease A Disease B Adjusted P-Value Shared Gene IDs
RHEUMATOID ARTHRITIS GRAFT-VERSUS-HOST DISEASE 3.24e-52 3807, ABCB1, ABCC1, ABCC2, ABO, ATIC, CCL2, CCL5, CCR5, CCR6, CD14, CD28, CD86, CTLA4, CYP2C19, EDN1, ESR1, ESR2, FAS, FASLG, FCGR2A, FCGR3A, FCRL3, GGH, GSTM1, GSTP1, GSTT1, GZMB, HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-G, HMHA1, HSPA1L, ICAM1, ICOS, IFNA1, IFNG, IFNGR1, IFNGR2, IL10, IL10RA, IL10RB, IL17A, IL17F, IL18, IL1A, IL1B, IL1R1, IL1RN, IL2, IL23R, IL4, IL4R, IL6, IL6R, IL7R, IRF1, ITGA4, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DP1, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KIR3DS1, LTA, MAPK14, MBD4, MBL2, MPG, MTHFR, NFKBIA, NOD2, NOS2, OGG1, PADI4, PARP1, PECAM1, PTPN22, PTPRC, RFC1, SELL, SLC19A1, SMAD3, TGFB1, TLR1, TLR10, TLR2, TLR3, TLR4, TLR5, TLR6, TLR8, TLR9, TNF, TNFRSF1A, TNFRSF1B, TNFSF13B, TYMS, UGT2B17, UNG, VDR, VEGFA, XRCC1
PSORIASIS GRAFT-VERSUS-HOST DISEASE 2.46e-43 3807, ABCB1, ABCC1, ATIC, CCL2, CCR5, CD14, CD28, CTLA4, CYP2C19, EDN1, FCGR2A, FCGR3A, FCRL3, GGH, GSTM1, GSTP1, GSTT1, HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-E, HLA-G, HSPA1L, IFNG, IL10, IL17A, IL17F, IL1A, IL1B, IL1R1, IL1RN, IL2, IL23R, IL4, IL4R, IL6, IL6R, IRF1, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DP1, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KIR3DS1, LTA, MBL2, MTHFR, NFKBIA, NOD2, NOS2, PADI4, PTPN22, RFC1, TGFB1, TLR10, TLR2, TLR4, TLR9, TNF, TNFRSF1A, TNFRSF1B, TYMS, VDR, VEGFA

Chemical, Pharmacological and Biological Annotations


ATC Code:
L04AD01 S01XA18;
Brand:
Sangcya
Categories:
Antirheumatic Agents; Dermatologic Agents; Immunosuppressive Agents; Antifungal Agents; Enzyme Inhibitors
ChEBI ID:
4031
KEGG Drug ID:
D00184
SMILE:
CCC1NC(=O)C(C(O)C(C)C\C=C\C)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C
InChI:
1/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+
Classification:
Kingdom:
Organic Compounds
Superclass:
Organic Acids and Derivatives
Class:
Carboxylic Acids and Derivatives
Subclass:
Amino Acids, Peptides, and Analogues
Indication:
For treatment of transplant (kidney, liver, and heart) rejection, rheumatoid arthritis, severe psoriasis.
Pharmacodynamics:
Used in immunosuppression for prophylactic treatment of organ transplants, cyclosporine exerts specific and reversible inhibition of immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhib...
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Description:
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Cyclosporine is produced...
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Mechanism:
Cyclosporine binds to cyclophilin. The complex then inhibits calcineurin which is normally responsible for activating transcription of interleukin 2. Cyclosporine also inhibits lymphokine production and interleukin release. In ophthalmic ap...
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Adsorption, Distribution, Metabolism, Excretion and Toxicity


Human Intestinal Absorption:
+
Blood Brain Barrier:
-
Caco-2 permeable:
-
P-glycoprotein substrate:
Substrate
P-glycoprotein inhibitor I:
Inhibitor
P-glycoprotein inhibitor II:
Non-inhibitor
Renal organic cation transporter:
Non-inhibitor
CYP450 2C9 substrate:
Non-inhibitor
CYP450 2D6 substrate:
Non-inhibitor
CYP450 2C19 substrate:
Non-inhibitor
CYP450 inhibitory promiscuity:
Low CYP Inhibitory Promiscuity
Ames test:
Non AMES toxic
Carcinogenicity:
Non-carcinogens
Biodegradation:
Not ready biodegradable
Rat acute toxicity:
2.8788 LD50, mol/kg
hERG inhibition (predictor I):
Weak inhibitor
hERG inhibition (predictor II):
Non-inhibitor

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Please contact us if you have questions or comments about RepurposeDB. You can also contact us if you need help in submitting your drug repositioning investigation to RepurposeDB.


Dudley Laboratory
Department of Genetics and Genomic Sciences
Icahn Institute for Genomics and Multiscale Biology
Icahn School of Medicine at Mount Sinai
One Gustave L. Levy Place, Box 1498
Manhattan, New York City, NY
repurposedb@dudleylab.org