Name: Cyclosporin A
Brand: BOC Sciences
Price: 292 USD
Availability: MadeToOrder

Purity

98%

Solubility

Soluble in Ethanol, Methanol, Chloroform, DMF, DMSO; Poorly soluble in Water

Appearance

Solid

Storage

4°C, protect from light

Sequence

cyclo[Abu-Sar-N(Me)Leu-Val-N(Me)Leu-Ala-D-Ala-N(Me)Leu-N(Me)Leu-N(Me)Val-N(Me)Bmt(E)]

IUPACName

(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone

Synonyms

Ciclosporin; cyclosporine; Cyclosporine A; Sandimmun; Cyclosporin; Neoral; Ciclosporine; Sandimmune; Ramihyphin A

Boiling Point

1293.8 °C at 760 mmHg

Melting Point

148-151 °C

Density

1.016 g/cm3

InChI Key

PMATZTZNYRCHOR-CGLBZJNRSA-N

InChI

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

SMILES

CCC1C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1)C(C(C)CC=CC)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C

Mechanism

E3 Ligase: Cyclosporin A does not function as a conventional molecular glue that directly recruits an E3 ligase such as CRBN or VHL. Instead, it binds to cyclophilin, forming a complex that can indirectly modulate ubiquitin ligase activity and protein turnover in specific cellular contexts.

Target Protein: The primary target of Cyclosporin A is calcineurin, a calcium/calmodulin-dependent serine/threonine phosphatase. By forming a cyclophilin–calcineurin complex, it alters the activity and stability of downstream substrates, indirectly affecting proteins that are normally regulated by ubiquitin-mediated degradation.

Degradation Mechanism: Cyclosporin A mediates protein turnover indirectly via the ubiquitin-proteasome system. The cyclophilin–calcineurin complex may influence the ubiquitination and proteasomal processing of interacting proteins, leading to selective degradation without directly triggering lysosomal pathways.

Applications

• Molecular Glue-Induced Ubiquitination: Cyclosporin A acts as a molecular glue, facilitating the ubiquitination of target proteins by bridging them with E3 ubiquitin ligases. This application is pivotal in research focused on understanding protein homeostasis and the selective degradation of proteins that are otherwise challenging to target.

• Targeted Protein Degradation Pathways: Researchers utilize Cyclosporin A to study pathways involved in targeted protein degradation. By promoting the formation of ternary complexes, it helps elucidate mechanisms of protein turnover, providing insights into cellular processes and potential therapeutic strategies for protein misfolding diseases.

• Modulation of Protein-Protein Interactions: Cyclosporin A serves as a molecular glue to modulate protein-protein interactions, enhancing the degradation of specific substrates. This application is essential for investigating the dynamics of protein complexes and their role in cellular signaling pathways, offering avenues for novel drug discovery.

• Enhancing Proteolytic Targeting: By functioning as a molecular glue, Cyclosporin A enhances the proteolytic targeting of specific proteins. This application is crucial for studying the selective degradation of proteins, aiding in the identification of new molecular targets for therapeutic intervention in diseases characterized by protein aggregation.

1.Amorphous cyclosporin A nanoparticles for enhanced dermal bioavailability.

Romero GB;Arntjen A;Keck CM;Müller RH Int J Pharm. 2016 Feb 10;498(1-2):217-24. doi: 10.1016/j.ijpharm.2015.12.019. Epub 2015 Dec 11.

Cylosporin A (CyA) was formulated as amorphous nanoparticle suspension to increase dermal penetration, e.g. applicable in psoriasis. The suspension consisted of 5% CyA in water, stabilized with vitamin E polyethylene glycol succinate (TPGS, Kolliphor TPGS) and was produced by bead milling. The diameter of the bulk population was about 350 nm, laser diffraction diameter 99% was 690 nm. The suspension was physically stable over one year of storage at room temperature, and most important the amorphous state also remained stable. Despite the high dispersitivity and related large surface area in contact with water, the drug content reduced only by 5% over 1 year of storage. i.e. the formulation is feasible as commercial product with expiry date. The CyA nanoparticles and μm-sized CyA particles were incorporated into hydroxypropylcellulose (HPC) gels and the penetration studied into fresh pig ear skin applying the tape stripping method. At tape number 30, the penetrated cumulative amount of CyA from nanoparticles was 6.3 fold higher compared to the μm-sized raw drug powder (450.1 μg/cm(2) vs. 71.3 μg/cm(2)). A theoretical mechanism is presented to explain the observed superiority in penetration.

2.[The efficacy and safety of modified busulfan/fludarabine conditioning regimen in elderly or drug-intolerable patients with hematologic malignancies].

Wang FR;Huang XJ;Liu DH;Chen H;Wang Y;Tang FF;Sun YQ;Fu HX;Liu KY;Xu LP Zhonghua Nei Ke Za Zhi. 2013 Dec;52(12):1028-32.

OBJECTIVE: ;To evaluate the efficacy and safety of modified busulfan (Bu, 9.6 mg/kg)/fludarabine (Flu) conditioning regimen on malignant hematologic diseases in elderly and/or drug-intolerable patients.;METHODS: ;We utilized a new reduced intensity conditioning (RIC) containing of new dosage of intravenous Bu (9.6 mg/kg), Flu (150 mg/m(2)), cytarabine and semustine but without antithymocyte globulin (ATG) in 23 aged and/or intolerable patients with malignancies. All 23 patients, with a median age of 49 (8-66) years, received an allogeneic hematopoietic stem cell transplantation with human leukocyte antigen (HLA) identical sibling donors during January 2008 and January 2012. Stem cells were collected from granulocyte colony-stimulation factor (G-CSF) mobilized bone marrow plus G-CSF mobilized peripheral blood(G-PB) in 20 patients, G-PB alone in two, and non-mobilized BM in one. The graft had a median mononuclear cells (MNC) of 7.03 (4.04-9.9)×10(8)/kg and 1.76 (0.31-6.43)×10(6)/kg of CD(+)34 cells. Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A, mycophenolate mofetil and methotrexate.;RESULTS: ;All patients were well tolerated to the regimen without serious drug related toxicity.

3.[Penetrating keratoplasty in high-risk children: prevention of graft rejection].

Pleskova AV;Khvatova AV Vestn Oftalmol. 2014 May-Jun;130(3):17-20.

PURPOSE: ;To evaluate the efficacy of prolonged courses of systemically administered subtherapeutic Metipred and cyclosporine in prevention of graft rejection in high-risk children.;MATERIAL AND METHODS: ;The study included 27 children at high risk of graft rejection due to re-keratoplasty (n = 8), limbo-keratoplasty for corneal staphyloma (n = 4), or transplantation into vascularized corneal bed (n = 15). All patients were divided into two groups--the study group (n =11) and the control group (n = 16). In order to evaluate the efficacy of two different prevention schemes, the occurrence of graft rejection, rejection crises, and crisis-associated clouding of the transplant was analyzed.;RESULTS: ;The occurrence of transplant opacity was two times lower in the Metipred-cyclosporine group than in the conventional prevention group. Kaplan-Meier one-year survival of the transplant was 53% in the study group and 27% in the control group. Two-year survival rate difference appeared even more significant--53% and 18% correspondingly.;CONCLUSION: ;It is clinically shown that subtherapeutic use of Metipred and cyclosporine decreases the occurrence of rejection crises and transplant failure almost by half in high-risk patients as compared with topical corticosteroids; at the same time the side effects of systemic immunosuppression are not substantial.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	0.8315 mL	4.1576 mL	8.3152 mL
5 mM	0.1663 mL	0.8315 mL	1.6630 mL
10 mM	0.0832 mL	0.4158 mL	0.8315 mL
50 mM	0.0166 mL	0.0832 mL	0.1663 mL

HNMR

HPLC

What is the mechanism of action of Cyclosporin A?

Cyclosporin A reversibly selectively alters the function of T lymphocytes, prevents the transcription of the lymphetin gene, interferes with the transmission of primitive information, and inhibits the release of interleukin-2, interferon, and other immune factors.

07/10/2019

Why do H2 receptor antagonists affect Cyclosporin A metabolism?

The H2 receptor antagonist liver inhibited the activity of cytochrome P-450 enzyme in cells.

09/1/2020

What are the physical properties of Cyclosporin A?

As a white solid with solubility of 30 mg/mL in methanol, Soluble in DMSO and Insoluble in water.

18/9/2022

Stock concentration: *

Desired final volume: *

Desired concentration: *

* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂