| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg | |||
| Other Sizes |
| Targets |
The primary target of Cyclosporin A-Derivative 1 Free base is expected to be the calcineurin pathway, similar to cyclosporin A. Cyclosporin A binds to cyclophilin, forming a complex that inhibits calcineurin, a calcium/calmodulin-dependent serine/threonine phosphatase. This inhibition prevents the dephosphorylation of nuclear factor of activated T-cells (NFAT), thereby blocking its translocation to the nucleus and subsequent transcription of genes required for T-cell activation, such as interleukin-2 (IL-2). By targeting this pathway, cyclosporin A and its derivatives exert potent immunosuppressive effects.
|
|---|---|
| ln Vitro |
Cyclosporin A-Derivative 1 is a non-immunosuppressive cyclosporin A derivative. Cyclosporine is acylated on the butenyl-methyl-threonine side chain, followed by a ring-opening process (the ring is opened between the sarcosine and N-methyl-leucine residues). Cyclosporin A-Derivative 1 is a linear peptide intermediate [1].
In vitro, Cyclosporin A-Derivative 1 Free base is expected to exhibit immunosuppressive activity by inhibiting T-cell activation. This activity would typically be assessed using cell-based assays, such as measuring the production of IL-2 or other cytokines in activated T-cells in the presence or absence of the compound. The compound's potency (IC50) and efficacy would be compared to those of cyclosporin A to determine whether the derivative offers any advantages. The compound may also be assessed for its effects on other immune cell types and its cytotoxicity. |
| ln Vivo |
In vivo, Cyclosporin A-Derivative 1 Free base has potential applications in studying immunosuppression in animal models of organ transplantation and autoimmune diseases. Its efficacy would be evaluated by measuring its ability to prolong graft survival or to reduce disease severity in animal models. Its pharmacokinetic properties and safety profile would also be assessed in these studies. The compound's potential advantages over cyclosporin A, such as reduced nephrotoxicity or improved oral bioavailability, would be key areas of investigation.
|
| Enzyme Assay |
Cell-free assays for Cyclosporin A-Derivative 1 Free base would typically involve assessing its inhibition of calcineurin activity. A common protocol involves incubating calcineurin with a phosphopeptide substrate and the compound at various concentrations in a reaction buffer containing calmodulin and calcium. The reaction is carried out at 30degC for a specified period, and the amount of phosphate released is measured using a colorimetric assay. The IC50 value is determined by plotting the percentage of enzyme activity remaining against the compound concentration. The binding affinity of the compound to cyclophilin can be assessed using surface plasmon resonance (SPR).
|
| Cell Assay |
For in vitro cellular experiments, T-cells (e.g., Jurkat cells, primary human T-cells) are cultured in appropriate media and activated with mitogens (e.g., PHA, anti-CD3/CD28) in the presence or absence of Cyclosporin A-Derivative 1 Free base at various concentrations (typically 0.1-100 uM). T-cell activation is assessed by measuring IL-2 production using ELISA or by measuring T-cell proliferation using [3H]-thymidine incorporation or CFSE dilution. Cell viability is assessed using MTT or CCK-8 assays to ensure that observed effects are not due to cytotoxicity.
|
| Animal Protocol |
In vivo animal experiments with Cyclosporin A-Derivative 1 Free base would typically involve oral or intraperitoneal administration in mouse or rat models of organ transplantation or autoimmune disease. A common dosing regimen would be 1-50 mg/kg body weight, administered daily. For transplantation studies, animals undergo organ or tissue transplantation, and the compound is administered to prevent rejection. Graft survival is monitored, and immune cell infiltration is assessed by histology. For autoimmune disease models, animals are treated with the compound, and disease progression is monitored using clinical scores, histology, and biochemical markers.
|
| ADME/Pharmacokinetics |
Cyclosporin A-Derivative 1 Free base is a synthetic derivative of cyclosporin A. As a small molecule, its pharmacokinetic properties would need to be characterized in preclinical studies, including absorption, distribution, metabolism, and excretion profiles. Key parameters such as oral bioavailability, half-life, plasma protein binding, and tissue distribution would be determined. The compound's lipophilic nature and structural similarity to cyclosporin A suggest that it may have similar pharmacokinetic properties, but this would need to be confirmed experimentally.
|
| Toxicity/Toxicokinetics |
The toxicity profile of Cyclosporin A-Derivative 1 Free base would need to be evaluated through a series of in vitro and in vivo toxicological studies. Cyclosporin A is known to have significant toxicities, including nephrotoxicity, hepatotoxicity, and hypertension. The derivative is being studied to determine whether it offers an improved safety profile with reduced toxicity. In vitro cytotoxicity assays in mammalian cell lines and in vivo toxicity studies in animal models would be required to assess its safety. The compound should be handled with standard laboratory precautions.
|
| References | |
| Additional Infomation |
Cyclosporin A-Derivative 1 Free base (CAS 286852-20-8) is a synthetic derivative of cyclosporin A, a well-known immunosuppressive drug. Cyclosporin A and its derivatives inhibit the calcineurin pathway, blocking T-cell activation by preventing NFAT translocation and subsequent IL-2 transcription. The derivative is likely being studied for its immunosuppressive properties with potentially improved efficacy, reduced toxicity, or altered pharmacokinetic properties compared to the parent compound. Cyclosporin A-Derivative 1 Free base is intended for research use only and is not approved for clinical use.
|
| Molecular Formula |
C65H117N11O14
|
|---|---|
| Molecular Weight |
1276.68979811668
|
| Exact Mass |
1275.878
|
| CAS # |
286852-20-8
|
| Related CAS # |
Cyclosporin A-Derivative 1;1487360-85-9
|
| PubChem CID |
88979347
|
| Appearance |
White to off-white solid powder
|
| LogP |
7.7
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
15
|
| Rotatable Bond Count |
40
|
| Heavy Atom Count |
90
|
| Complexity |
2430
|
| Defined Atom Stereocenter Count |
12
|
| SMILES |
O(C(C)=O)[C@H]([C@H](C)C/C=C/C)[C@@H](C(N[C@H](C(N(C)CC(=O)OC)=O)CC)=O)N(C)C([C@H](C(C)C)N(C)C([C@H](CC(C)C)N(C)C([C@H](CC(C)C)N(C)C([C@@H](C)NC([C@H](C)NC([C@H](CC(C)C)N(C)C([C@H](C(C)C)NC([C@H](CC(C)C)NC)=O)=O)=O)=O)=O)=O)=O)=O
|
| InChi Key |
PSOOLRRRIPXEQE-VFELDGILSA-N
|
| InChi Code |
InChI=1S/C65H117N11O14/c1-27-29-30-42(15)55(90-45(18)77)54(59(82)69-46(28-2)61(84)71(20)35-51(78)89-26)76(25)65(88)53(41(13)14)75(24)63(86)50(34-39(9)10)74(23)62(85)49(33-38(7)8)73(22)60(83)44(17)68-56(79)43(16)67-58(81)48(32-37(5)6)72(21)64(87)52(40(11)12)70-57(80)47(66-19)31-36(3)4/h27,29,36-44,46-50,52-55,66H,28,30-35H2,1-26H3,(H,67,81)(H,68,79)(H,69,82)(H,70,80)/b29-27+/t42-,43+,44-,46+,47+,48+,49+,50+,52+,53+,54+,55-/m1/s1
|
| Chemical Name |
methyl 2-[[(2S)-2-[[(E,2S,3R,4R)-3-acetyloxy-4-methyl-2-[methyl-[(2S)-3-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2R)-2-[[(2S)-2-[[(2S)-4-methyl-2-[methyl-[(2S)-3-methyl-2-[[(2S)-4-methyl-2-(methylamino)pentanoyl]amino]butanoyl]amino]pentanoyl]amino]propanoyl]amino]propanoyl]amino]pentanoyl]amino]pentanoyl]amino]butanoyl]amino]oct-6-enoyl]amino]butanoyl]-methylamino]acetate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~78.33 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7833 mL | 3.9164 mL | 7.8328 mL | |
| 5 mM | 0.1567 mL | 0.7833 mL | 1.5666 mL | |
| 10 mM | 0.0783 mL | 0.3916 mL | 0.7833 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
