CYCLOSPORINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C62H111N11O12
Molecular Weight	1202.6112
Optical Activity	( - )
Defined Stereocenters	12 / 12
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C

InChI

InChIKey=PMATZTZNYRCHOR-CGLBZJNRSA-N

InChI=1S/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+/t40-,41+,42-,43+,44+,45+,46+,47+,49+,50+,51+,52-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C62H111N11O12
Molecular Weight	1202.6112
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry
Defined Stereocenters	12 / 12
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description

Cyclosporins are cyclic polypeptide macrolides that were originally derived from the soil fungus Tolypocladium inflatum. Cyclosporine (also known as cyclosporine A) was discovered by Sandoz and developed for the tretment of immune disorders. The drug was approved by FDA for such diseases as Rheumatoid Arthritis, Psoriasis (Neoral), Keratoconjunctivitis sicca (Restasis) and prevention of transplant rejections (Neoral and Sandimmune). Cyclosporine’s primary immunosuppressive mechanism of action is inhibition of T-lymphocyte function. Upon administration cyclosporine binds to cyclophilin A and thus inhibits calcineurin, leading to immune system suppression.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclophilin A 1	Binding Agent 964	Psoriasis	36.8 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Psoriasis 118	Primary	Cyclophilin A	Approved 7888	NEORAL
Arthritis, Rheumatoid 146	Primary	Cyclophilin A	Approved 7888	NEORAL
Keratoconjunctivitis Sicca 2	Palliative	Cyclophilin A	Approved 7888	RESTASIS
Graft Rejection 2	Preventing	Cyclophilin A	Approved 7888	SANDIMMUNE
Atopic dermatitis 3			Approved (off-label) 8
[Fungal eye infections, Epidemic keratoconjunctivitis, Stromal keratitis, Stevens-Johnson syndrome] 1			Approved (off-label) 8

PubMed

Title	Date	PubMed
Nephrotoxicity after orthotopic liver transplantation in cyclosporin A and FK 506-treated patients.	1994	11271297
Renal complications and development of hypertension in the European study of FK 506 and cyclosporin in primary liver transplant recipients.	1994	11271207
Acute myopathy induced by colchicine in a cyclosporine treated heart transplant recipient: possible role of the multidrug resistance transporter.	1999 Aug	10455999
Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity.	1999 Dec	10565843
Relation between long-term steroid treatment after heart transplantation, hypofibrinolysis and myocardial microthrombi generation.	1999 Jul	10452346
Aplastic anemia responsive to cyclosporine complicating the evolution of polycythemia vera.	1999 May	10342591
Enhancement of low density lipoprotein catabolism by non-steroidal anti-inflammatory drugs in cultured HepG2 cells.	1999 May 21	10395027
Which calcineurin inhibitor is preferred in renal transplantation: tacrolimus or cyclosporine?	1999 Nov	10630811
Hemolytic-uremic syndrome in association with both cyclosporine and tacrolimus.	2000	11140243
Rhabdomyolysis and acute renal failure in a cardiac transplant recipient due to multiple drug interactions.	2000 Dec	11149552
Cyclosporine withdrawal in stable renal transplant recipients after azathioprine-mycophenolate mofetil conversion.	2000 Dec	11127309
Suppressive effects of cyclosporin A and FK-506 on superoxide generation in human polymorphonuclear leukocytes primed by tumor necrosis factor alpha.	2000 Dec	11121130
Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappaB activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis.	2000 Jan 21	10636889
Comparison of enalapril and valsartan in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet.	2000 Jul	10903974
Phenytoin and cyclosporin A suppress the expression of MMP-1, TIMP-1, and cathepsin L, but not cathepsin B in cultured gingival fibroblasts.	2000 Jun	10914799
Ticlopidine-induced aplastic anemia: development of chromosomal abnormalities and response to immunosuppressive therapy.	2000 Mar	10679804
Design of a Gag pentapeptide analogue that binds human cyclophilin A more efficiently than the entire capsid protein: new insights for the development of novel anti-HIV-1 drugs.	2000 May 4	10794694
Tacrolimus has less fibrogenic potential than cyclosporin A in a model of renal ischaemia-reperfusion injury.	2000 Nov	11091246
Fatal cerebral hemorrhage associated with cyclosporin-A/FK506-related encephalopathy after allogeneic bone marrow transplantation.	2000 Oct	11100753
Cyclosporine and tacrolimus-associated thrombotic microangiopathy.	2000 Oct	11007689
Toxic epidermal necrolysis in a patient with severe aplastic anemia treated with cyclosporin A and G-CSF.	2001	11321886
Renal cholesterol accumulation: a durable response after acute and subacute renal insults.	2001 Aug	11485932
Calcineurin-inhibitor related nephrotoxicity- reversibility in paediatric liver transplant recipients.	2001 Aug 27	11544444
Bone marrow aplasia after pipobroman: an immune-mediated mechanism?	2001 Dec	11736962
End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.	2001 Dec 27	11773892
Mycophenolate mofetil monotherapy in liver transplantation.	2001 Feb 24	11558493
Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy.	2001 Jul	11472356
Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis.	2001 Nov	11692113
Buerger's disease in a patient with minimal-change nephrotic syndrome.	2001 Nov	11598405
Severe neurotoxicity of tacrolimus (FK506) after renal transplantation: two case reports.	2001 Nov-Dec	11750573
Cyclosporin A-induced encephalopathy after allogeneic bone marrow transplantation with prevention of graft-versus-host disease by tacrolimus.	2001 Oct	11704797
Use of rapamycin in a transplant patient who developed cyclosporin neurotoxicity.	2001 Oct	11605780
Sirolimus and mycophenolate mofetil for calcineurin-free immunosuppression in renal transplant recipients.	2001 Oct	11583940
Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus.	2001 Oct	11583721
Sirolimus: new preparation. No tangible advance in renal transplantation.	2002 Dec	12469693
Expression of TGF-beta and fibrogenic genes in transplant recipients with tacrolimus and cyclosporine nephrotoxicity.	2002 Dec	12427154
Colchicine myoneuropathy in a renal transplant patient.	2002 Jul	12122515
Calcineurin inhibitors, cyclosporin A and tacrolimus inhibit expression of inducible nitric oxide synthase in colon epithelial and macrophage cell lines.	2002 Jul 19	12144947
Enhancement by cyclosporin A of taxol-induced apoptosis of human urinary bladder cancer cells.	2002 May	12086014
Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril.	2002 Oct	12352326
Long-term comparison of tacrolimus- and cyclosporine-induced nephrotoxicity in pediatric heart-transplant recipients.	2002 Sep	12243498

Patents

Sample Use Guides

In Vivo Use Guide

Organs transplantation: the initial oral dose of cyclosporine (Sandimmune) should be given 4 to 12 hours prior to transplantation as a single dose of 15 mg/kg. Rheumatoid Arthritis, Psoriasis: the initial dose of cyclosporine (Neoral) is 2.5 mg/kg/day, taken twice daily as a divided (BID) oral dose. Keratoconjunctivitis sicca: instill one drom twice a day in each eye, approximately 12 hours apart.

Route of Administration: Oral; Ophthalmic

In Vitro Use Guide

Human CD4+CD25+ cells isolated from healthy donors were cultured in the presence of 40 or 400 ng/mL of cyclosporine. The suppressive activity of Treg was assessed in mixed leukocyte reactions (MLR) using CD25+ and autologous activated peripheral blood mononuclear cells (PBMC). The drug inhibited the proliferative capacity of PBMC and CD4+CD25+ Treg in a dose-dependent manner.

Substance Class	Chemical Created by `admin` on `Mon Oct 21 20:41:45 UTC 2019` Edited by `admin` on `Mon Oct 21 20:41:45 UTC 2019`
Record UNII	83HN0GTJ6D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CYCLOSPORINE

Official Name

English

CYCLOSPORIN A [MI]

Common Name

English

CICLOSPORINUM [WHO-IP LATIN]

Common Name

English

EQUORAL

Common Name

English

CYCLOSPORIN

Common Name

English

CYCLOSPORINE [GREEN BOOK]

Common Name

English

CICLOSPORIN A

Common Name

English

GENGRAF

Brand Name

English

RAMIHYPHIN A

Common Name

English

(R-(R*,R*-(E)))-CYCLIC(L-ALANYL-D-ALANYL-N-METHYL-L-LEUCYL-N-METHYL-L-LEUCYL-N-METHYL-L-VALYL-3-HYDROXY-N,4-DIMETHYL-L-2-AMINO-6-OCTENOYL-L-.ALPHA.-AMINOBUTYRYL-N-METHYLGLYCYL-N-METHYL-L-LEUCYL-L-VALYL-N-METHYL-L-LEUCYL)

Common Name

English

NSC-290193

Code

English

NEOPLANTA

Common Name

English

SANDIMMUNE

Brand Name

English

NEORAL

Brand Name

English

SDZ-OXL-400

Code

English

MITOGARD

Brand Name

English

OL-27-400

Code

English

NEUROSTAT

Brand Name

English

CYCLOSPORINE [USP-RS]

Common Name

English

CICLOSPORIN [EP]

Common Name

English

ATOPICA

Brand Name

English

CYCLOSPORINE [HSDB]

Common Name

English

OPTIMMUNE

Brand Name

English

CYCLOSPORINE [USP]

Common Name

English

CYCLO(((E)-(2S,3R,4R)-3-HYDROXY-4-METHYL-2-(METHYLAMINO)-6-OCTENOYL)-L-2-AMINOBUTYRYL-N-METHYLGLYCYL-N-METHYL-L-LEUCYL-L-VALYL-N-METHYL-L-LEUCYL-L-ALANYL-D-ALANYL-N-METHYL-L-LEUCYL-N-METHYL-L-LEUCYL-N-METHYL-L-VALYL)

Common Name

English

CYCLOSPORINE MICROEMULSION

Common Name

English

CICLOSPORIN [WHO-DD]

Common Name

English

IKERVIS

Brand Name

English

CYCLOSPORINE [IARC]

Common Name

English

CYCLOSPORINE, MODIFIED

Common Name

English

CYCLOSPORINE [VANDF]

Common Name

English

ANTIBIOTIC S-7481F1

Code

English

CICLOSPORIN [JAN]

Common Name

English

CYCLOSPORINE [USAN]

Common Name

English

CICLOSPORIN

Official Name

English

CICLOSPORIN [INN]

Common Name

English

CYCLOSPORIN A

Common Name

English

SANG-35

Code

English

27-400

Code

English

CEQUA

Brand Name

English

CYCLOSPORINE [ORANGE BOOK]

Common Name

English

CYCLOSPORINE A

Common Name

English

CICLOSPORIN [WHO-IP]

Common Name

English

RESTASIS

Brand Name

English

ZINOGRAF ME

Common Name

English

SANDIMMUN

Brand Name

English

CICLOSPORIN [MART.]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QS01XA18