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| Targets |
Cevidoplenib dimesylate targets spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase that plays a critical role in immune cell signaling. Syk is involved in the activation of B cells, mast cells, macrophages, and other immune cells through immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling. By inhibiting Syk, Cevidoplenib blocks downstream signaling pathways that lead to the production of autoantibodies and inflammatory mediators. The compound has an IC50 of 6.2 nM for Syk.
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| ln Vitro |
Cevidoplenib dimesylate demonstrates potent in vitro activity as a Syk inhibitor with an IC50 of 6.2 nM. It selectively inhibits Syk kinase activity in biochemical assays. In cell-based systems, the compound inhibits Syk-dependent signaling pathways, including B cell receptor (BCR) and Fc receptor signaling. By inhibiting both autoantibody-producing and autoantibody-sensing cells, Cevidoplenib effectively suppresses immune cell activation and the production of inflammatory cytokines.
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| ln Vivo |
Cevidoplenib dimesylate exhibits in vivo activity in animal models of autoimmune diseases. As an orally available Syk inhibitor, it attenuates the progression of autoantibody-mediated autoimmune diseases by inhibiting both autoantibody-producing and autoantibody-sensing cells. The compound has demonstrated efficacy in preclinical models of immune-mediated inflammatory conditions. Its oral bioavailability and anti-inflammatory activity make it a promising candidate for the treatment of autoimmune disorders.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for Cevidoplenib dimesylate involves assessing its inhibition of Syk kinase activity. Recombinant Syk kinase is incubated with the compound, ATP, and a substrate peptide. Kinase activity is measured by detecting phosphorylated substrate using techniques such as radiometric assays, fluorescence-based assays, or ELISA. The IC50 value of 6.2 nM is determined from dose-response curves. Selectivity profiling against other kinases is also performed to confirm its specificity.
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| Cell Assay |
The in vitro cell-based assay for Cevidoplenib dimesylate involves treating immune cells (such as B cells, mast cells, or macrophages) with the compound and measuring Syk-dependent signaling and functional responses. Cells are stimulated through immunoreceptors (e.g., BCR or Fc receptors), and downstream phosphorylation of Syk and its substrates is assessed by Western blotting or phospho-flow cytometry. Cytokine production and cell activation markers are also measured to evaluate the compound’s immunomodulatory effects.
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| Animal Protocol |
In vivo animal experiments for Cevidoplenib dimesylate are conducted in autoimmune disease models to evaluate its efficacy. Animals are administered the compound orally at various doses, and disease progression is monitored through clinical scores, histopathological analysis, and measurement of autoantibody levels. The compound’s ability to attenuate autoantibody-mediated tissue damage and inflammation is assessed. Pharmacodynamic markers such as Syk phosphorylation in immune cells may also be measured.
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| ADME/Pharmacokinetics |
Cevidoplenib dimesylate is an orally bioavailable compound. The dimesylate salt form (SKI-O-703) is designed to enhance oral absorption and bioavailability. The compound has a molecular weight of 665.74 g/mol and a molecular formula of C27H35N7O9S2. It is soluble in DMSO (100 mg/mL) and water (12 mg/mL) but insoluble in ethanol. Further pharmacokinetic studies are needed to fully characterize its half-life, clearance, and volume of distribution.
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| Toxicity/Toxicokinetics |
Toxicological data for Cevidoplenib dimesylate are not extensively documented in the available literature. As a research compound intended for preclinical studies, its safety profile is evaluated in standard toxicology assays. The compound is classified for research use only and is not intended for human therapeutic use. Comprehensive toxicological characterization would be required prior to any clinical development.
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| References | |
| Additional Infomation |
Cevidoplenib Dimesylate is the dimethylsulfonate salt of cefdopril, an orally potent spleen tyrosine kinase (SYK) inhibitor with potential anti-inflammatory and immunomodulatory activities. After oral administration, cefdopril binds to SYK and inhibits its activity, thereby blocking Fc receptor and B cell receptor (BCR)-mediated signaling in inflammatory cells, including macrophages, neutrophils, mast cells, natural killer (NK) cells, and B cells. This leads to suppression of activation of these inflammatory cells and reduces associated inflammatory responses and tissue damage. SYK is a non-receptor cytoplasmic protein tyrosine kinase widely expressed in hematopoietic cells and plays a crucial role in Fc receptor and B cell receptor signaling in inflammatory cells. It is involved in coupling activated immune receptors (such as Fc receptors and B cell receptors) to send downstream signals that mediate various cellular responses, including proliferation, differentiation, and phagocytosis, which are important for allergic diseases and antibody-mediated immune diseases (such as immune thrombocytopenic purpura (ITP)).
Cevidoplenib dimesylate (SKI-O-703 dimesylate, CAS 2043659-93-2) is an orally available, potent, and selective Syk inhibitor with anti-inflammatory and immunomodulating activities. It has a molecular weight of 665.74 g/mol and a formula of C27H35N7O9S2. The compound is primarily used in research on autoimmune diseases. It is not approved for clinical use and is available only for research purposes. The purity is ≥98%. |
| Molecular Formula |
C27H35N7O9S2
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|---|---|
| Molecular Weight |
665.738303422928
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| Exact Mass |
665.193
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| CAS # |
2043659-93-2
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| Related CAS # |
Cevidoplenib;1703788-21-9
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| PubChem CID |
137528229
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| Appearance |
Yellow to brown solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
45
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| Complexity |
862
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S(C)(=O)(=O)O.S(C)(=O)(=O)O.O=C(C1=CN(C)C2C=CC(=CC1=2)NC1N=CC=C(N=1)N1C=C(C(C)=N1)CN1C[C@@H](CO1)O)C1CC1
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| InChi Key |
KGZICKLRNSIYNH-TXEPZDRESA-N
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| InChi Code |
InChI=1S/C25H27N7O3.2CH4O3S/c1-15-17(10-31-12-19(33)14-35-31)11-32(29-15)23-7-8-26-25(28-23)27-18-5-6-22-20(9-18)21(13-30(22)2)24(34)16-3-4-16;2*1-5(2,3)4/h5-9,11,13,16,19,33H,3-4,10,12,14H2,1-2H3,(H,26,27,28);2*1H3,(H,2,3,4)/t19-;;/m0../s1
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| Chemical Name |
cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone;methanesulfonic acid
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 25 mg/mL (37.55 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.76 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5021 mL | 7.5104 mL | 15.0209 mL | |
| 5 mM | 0.3004 mL | 1.5021 mL | 3.0042 mL | |
| 10 mM | 0.1502 mL | 0.7510 mL | 1.5021 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04057118
Conditions:Rheumatoid ArthritisLink: https://clinicaltrials.gov/ct2/show/NCT04056195
Conditions:Immune ThrombocytopeniaLink: https://clinicaltrials.gov/ct2/show/NCT02717988
Conditions:Rheumatoid Arthritis
Title:Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SKI-O-703 in Healthy Volunteers
Status:Completed
updateDate:2017-10-20
Ctid:NCT03315494
Link: https://clinicaltrials.gov/ct2/show/NCT03315494
Conditions:Arthritis, RheumatoidProducts are for research use only; We do not sell to patients
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