| Size | Price | Stock | Qty |
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| 5mg |
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CYM50358 HCl, the hydrochloride salt of CYM-50358, is a potent S1P4 antagonist with an IC50 of 25 nM, and is selective for S1P4 against S1P1, S1P2, S1P3 and S1P5 receptors.
CYM50358 (compound 4v) is a selective sphingosine-1-phosphate 4 (S1P4) receptor antagonist discovered through high-throughput screening and subsequent structure-activity relationship (SAR) optimization of a 5-aryl furan-2-arylcarboxamide hit compound. It was identified as one of the first reported potent and selective S1P4 antagonists with low nanomolar activity and adequate physicochemical properties. CYM50358 has been used as a pharmacological tool to elucidate the biological role of S1P4. In human platelets, it was shown to reverse the S1P-induced suppression of collagen-stimulated HSP27 phosphorylation, confirming that the inhibitory effects of S1P on platelet activation are mediated through S1PR4. [1][2]| Targets |
- Sphingosine-1-phosphate 4 receptor (S1P4): CYM50358 is a selective S1P4 antagonist. [1][2]
- In vitro potency (IC50) at S1P4: 256 nM (antagonist activity). [1]
- Selectivity: No significant activity at S1P1, S1P2, S1P3, or S1P5 receptors at concentrations up to 25 μM. [1]
- S1P1: 5% inhibition at 25 μM. [1]
- S1P2: 95% inhibition at 25 μM (IC50 = 3900 nM). [1]
- S1P3: Not active at concentrations up to 25 μM (showed 30% inhibition at 25 μM). [1]
- S1P5: 90% inhibition at 25 μM (IC50 = 5500 nM). [1]
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| ln Vitro |
- S1P4 Antagonist Activity: CYM50358 (compound 4v) showed potent S1P4 antagonist activity with an IC50 of 256 nM in a functional assay. It demonstrated high selectivity against other S1P receptor subtypes (S1P1-3,5), with no significant activity at S1P1 and S1P3 up to 25 μM. [1]
- Physicochemical Properties: The compound has a calculated Log P (cLog P) of 4.7 and a total polar surface area (tPSA) of 47.6. [1] - Effect on Platelet HSP27 Phosphorylation (as an antagonist): In human platelets, CYM50358 (10 μM) alone had no effect on collagen-induced HSP27 (Ser-78) phosphorylation. However, it markedly reversed the suppressive effect of S1P (30 μM) on collagen-induced HSP27 phosphorylation, almost restoring it to the levels of collagen alone. This confirms that S1P's inhibitory effect is mediated through S1PR4. [2] |
| Enzyme Assay |
- S1P4 Functional Assay (Tango™ EDG6-bla U2OS cells): The activity was measured using Tango™ EDG6-bla U2OS cells which contain the human Endothelial Differentiation Gene 6 (S1P4) linked to a GAL4-VP16 transcription factor via a TEV protease site. The cells also express a β-arrestin/TEV protease fusion protein and a β-lactamase (BLA) reporter gene under the control of a UAS response element. BLA expression is monitored by measuring fluorescence resonance energy transfer (FRET) of a cleavable, fluorogenic, cell-permeable BLA substrate. [1]
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| Cell Assay |
- Platelet Aggregation and Activation Studies (Human Platelets): Human platelets were prepared from blood drawn from healthy volunteers. Platelet-rich plasma (PRP) was obtained by centrifugation. To study the antagonist effect, PRP was pretreated with CYM50358 (10 μM) or vehicle for 1 minute, then pretreated with S1P (30 μM) or vehicle for 15 minutes, and finally stimulated with collagen for 90 seconds. The reaction was terminated by adding ice-cold EDTA, and platelet extracts were subjected to SDS-PAGE and Western blot analysis using antibodies against phospho-specific HSP27 (Ser-78) and GAPDH. [2]
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| ADME/Pharmacokinetics |
The calculated physicochemical properties (cLog P = 4.7, tPSA = 47.6) were reported as part of the lead optimization process to assess drug-like properties. [1]
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| References |
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| Additional Infomation |
- Chemical Identity: CYM50358 is the designated name for compound 4v in the structure-activity relationship study. Its structure is based on a 5-aryl furan-2-arylcarboxamide scaffold. [1]
- Discovery: It was discovered through high-throughput screening of the Molecular Libraries-Small Molecule Repository (MLSMR) collection, followed by systematic SAR optimization to improve potency and reduce lipophilicity from the initial hit compound. [1] - Use as a Pharmacological Tool: CYM50358 is the first reported potent and selective S1P4 antagonist. It serves as a valuable tool for elucidating the biological and pharmacological functions of the S1P4 receptor, particularly in studies where blocking S1P4 signaling is required. [1][2] - Role in Platelet Studies: In human platelets, CYM50358 was used to demonstrate that the inhibitory effect of exogenous S1P on collagen-induced platelet activation (specifically HSP27 phosphorylation) is mediated specifically through the S1P4 receptor, not S1P1. [2] |
| Molecular Formula |
C20H19CL3N2O2
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|---|---|
| Molecular Weight |
425.73
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| Exact Mass |
424.051
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| CAS # |
1781750-72-8
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| Related CAS # |
1314212-39-9;1781750-72-8 (HCl);
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| PubChem CID |
78243726
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
480
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1C1=C([H])C([H])=C(C(N([H])C2C(C([H])([H])[H])=C([H])C(C([H])([H])N([H])[H])=C([H])C=2C([H])([H])[H])=O)O1)Cl.Cl[H]
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| InChi Key |
OFDSTJOMVDAKCS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H18Cl2N2O2.ClH/c1-11-7-13(10-23)8-12(2)19(11)24-20(25)18-6-5-17(26-18)15-9-14(21)3-4-16(15)22/h3-9H,10,23H2,1-2H3,(H,24,25)1H
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| Chemical Name |
N-(4-(aminomethyl)-2,6-dimethylphenyl)-5-(2,5-dichlorophenyl)furan-2-carboxamide hydrochloride
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| Synonyms |
CYM50358 HCl; CYM50358 HCl; CYM50358 hydrochloride; 1781750-72-8; CYM50358 HCl; CYM50358 (hydrochloride); N-(4-(aminomethyl)-2,6-dimethylphenyl)-5-(2,5-dichlorophenyl)furan-2-carboxamide hydrochloride; CYM-50358 HCl; CYM-50358 hydrochloride
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3489 mL | 11.7445 mL | 23.4891 mL | |
| 5 mM | 0.4698 mL | 2.3489 mL | 4.6978 mL | |
| 10 mM | 0.2349 mL | 1.1745 mL | 2.3489 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.
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