| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg |
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| Other Sizes |
| Targets |
N-type (Cav2.2) calcium channels (EC50 = 7.21 ± 0.86 µM)
P/Q-type (Cav2.1) calcium channels (EC50 = 8.8 ± 1.1 µM) L-type (Cav1.3) calcium channels (EC50 > 100 µM) Cyclin-dependent kinase 2 (Cdk2) (IC50 = 3.29 ± 0.43 µM) Cyclin-dependent kinase 5 (Cdk5) (IC50 = 3.03 ± 0.32 µM) Cyclin-dependent kinase 1 (Cdk1) (IC50 > 20 µM) Mitogen-activated protein kinase 1 (MAPK1) (IC50 > 20 µM) Myosin light-chain kinase (MLCK) (IC50 > 20 µM). [1] |
|---|---|
| ln Vitro |
Ca2+ channel agonist 1 (Compound 13d) has an EC50 of 3.34 μM and 14.23 μM, respectively, making it an inhibitor of Cdk2 and an agonist of N-type Ca2+ channels. A1: Ca2+ channel agonist displays ca. Agonism is increased twofold and cdk2 kinase activity is decreased twenty-twofold when compared to standard (R)-roscovitine [1].
13x is a synthetic analogue of (R)-roscovitine. [1] In whole-cell patch-clamp recordings, 13x acted as an agonist for N-type calcium channels with an EC50 of 7.21 ± 0.86 µM, representing approximately a 4-fold improvement in agonist efficacy compared to (R)-roscovitine (EC50 = 27.58 ± 1.65 µM). [1] 13x also acted as an agonist for P/Q-type calcium channels with an EC50 of 8.8 ± 1.1 µM, but showed no agonist activity on L-type calcium channels up to 100 µM, indicating selectivity for N- and P/Q-type over L-type channels. [1] In a kinase inhibition panel, 13x showed an IC50 of 3.29 ± 0.43 µM against Cdk2, which is approximately a 22-fold decrease in inhibitory activity compared to (R)-roscovitine (IC50 = 0.151 ± 0.004 µM). Its IC50 against Cdk5 was 3.03 ± 0.32 µM, against Cdk1 was >20 µM, and it showed no significant inhibition (IC50 >20 µM) of MAPK1 or MLCK. [1] |
| Enzyme Assay |
The inhibitory activities of 13x and reference compounds against Cdk1/cyclinB(h), Cdk2/cyclinA(h), Cdk5/p35(h), MAPK1(h), and MLCK(h) were determined by a commercial service. The assays were performed at three different concentrations of the agent (0.2, 2, and 20 µM), with (R)-roscovitine included as a positive control. IC50 values were derived from the results. [1]
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| Cell Assay |
The effects of 13x and other (R)-roscovitine derivatives on calcium channels were evaluated using whole-cell perforated patch-clamp recordings. The pipette solution contained Cs₂SO₄, CsCl, MgCl₂, and HEPES (pH 7.4). Cells were bathed in a saline solution containing choline chloride, TEA-Cl, CaCl₂, MgCl₂, and HEPES (pH 7.4). Patch pipettes were fabricated from borosilicate glass. Capacitive currents and passive membrane responses were subtracted. Currents were amplified, filtered at 5 kHz, and digitized at 10 kHz for analysis. A liquid junction potential was corrected during recordings. To measure effects on calcium channel tail currents, the tail current integral was measured before and after compound application, with each trace normalized to its peak. All experiments were conducted at room temperature (22°C). Compounds were dissolved in DMSO as 100 mM stocks and stored at -20°C. For recordings, compounds were diluted in saline to final concentrations of 1–100 µM and applied via bath perfusion. Control experiments with DMSO alone showed no significant effects. [1]
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| References | |
| Additional Infomation |
13x was developed by modifying the purine skeleton of (R)-roscovitine and conducting a systematic structure-activity relationship (SAR) study. Its goal is to improve the selectivity and potency of N-type and P/Q-type voltage-gated calcium channel agonists while reducing their inhibitory activity on cyclin-dependent kinases (Cdk). [1]
The synthesis of 13x started with 2,6-dichloropurine. First, alkylation was performed at the N-9 position to introduce n-propyl (R¹), and then a nucleophilic aromatic substitution reaction was carried out at the C-6 position using (2-methyl-5-thienyl)methylamine as a substituent. Finally, the chlorine atom at the C-2 position was replaced with (R)-2-amino-1-butanol to obtain the target compound. [1] In order to analyze the structural basis of the reduced inhibitory activity of the analog 13xCdk2, we conducted molecular docking studies on the Cdk2/(R)-roscovitine complex. Docking posture and binding score (MolDock score) were consistent with experimental trends, indicating reduced kinase inhibition. [1] The long-term goal of developing such selective calcium channel agonists is for the treatment of Lambert-Eaton myasthenia gravis (LEMS) and other neurological disorders. The mechanism involves a direct increase in calcium ion influx into presynaptic N-type and P/Q-type channels during action potentials, thereby enhancing neurotransmitter release and compensating for channel loss in LEMS. [1] Based on clinical experience with the indirect potassium channel blocker 3,4-diaminopyridine (DAP) in Lambert-Eaton myasthenia gravis (LEMS), selective use of dependent N-type and P/Q-type calcium channel agonists such as 13x is expected to be well-tolerated, provided they do not cross the blood-brain barrier. [1] 13x is also considered a useful experimental tool for studying the fundamental properties of P/Q-type and N-type calcium channels and the regulation of neurotransmitter release by calcium. [1] |
| Molecular Formula |
C19H26N6O
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|---|---|
| Molecular Weight |
354.4493
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| Exact Mass |
354.216
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| CAS # |
1402821-24-2
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| PubChem CID |
69472592
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
26
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| Complexity |
406
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O([H])C([H])([H])[C@@]([H])(C([H])([H])C([H])([H])[H])N([H])C1=NC(=C2C(=N1)N(C([H])=N2)C([H])([H])C([H])([H])C([H])([H])[H])N([H])C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H]
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| InChi Key |
LKXPLOHGQSEPEM-OAHLLOKOSA-N
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| InChi Code |
InChI=1S/C19H26N6O/c1-3-10-25-13-21-16-17(20-11-14-8-6-5-7-9-14)23-19(24-18(16)25)22-15(4-2)12-26/h5-9,13,15,26H,3-4,10-12H2,1-2H3,(H2,20,22,23,24)/t15-/m1/s1
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| Chemical Name |
(2R)-2-[[6-(benzylamino)-9-propylpurin-2-yl]amino]butan-1-ol
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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) |
DMSO : ~50 mg/mL (~141.06 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.05 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 (7.05 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 | 2.8213 mL | 14.1064 mL | 28.2127 mL | |
| 5 mM | 0.5643 mL | 2.8213 mL | 5.6425 mL | |
| 10 mM | 0.2821 mL | 1.4106 mL | 2.8213 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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