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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Purity: ≥98%
IBMX is a nonspecific, broad-spectrum, competitive inhibitor of phosphodiesterase (PDE) inhibitor, with IC50s of 6.5, 26.3 and 31.7 μM for PDE3, PDE4 and PDE5, respectively. It enhances the intracellular cAMP levels and also acts as an adenosine (A1) receptor antagonist. IBMX raises intracellular cAMP, activates PKA, inhibits TNFα and leukotriene synthesis, and reduces inflammation and innate immunity. IBMX, a non-selective PDE inhibitor significantly decreases the liver glycogen storage (mg/g, IBMX 22±1.5 P<0.001). IBMX potentiates insulin release and in hepatocytes and adipocytes, they increase glycogenolysis and lipolysis. Pretreatment of CCDs (cortical collecting duct) with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels.
Targets |
PDE3 (IC50 = 6.5 μM); PDE4 (IC50 = 26.3 μM); PDE5 (IC50 = 31.7 μM)
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ln Vitro |
The most efficient concentrations for inducing airway relaxation were 100 μM for both KMUP-1 (a xanthine peptide inducer) and IBMX; there was no discernible variation in the activation of the induction response triggered by either compound [1]. Renal outer medulla K+ (ROMK) channels were activated (n=6, P<0.05) by IBMX (100 μM), while ANG II (n=6, P=NS) or cGMP could not further activate these channels. Notably, tubular cAMP content increased significantly to 1.43±0.35 pg/mm tubule length (n =14) after 20 minutes of sham-containing nutrient collecting ducts (CCDs) isolated from high K+ (HK)-fed scaffolds with IBMX (100 μM) compared to tubule length measured in vehicle-treated controls (0.61±0.13 pg/mm tubule length, n =12, P<0.05)[2].
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ln Vivo |
Liver glycogen reserves are considerably reduced by IBMX, a non-selective PDE (mg/g, IBMX 22±1.5 P<0.001). IBMX and mc5 were found to significantly increase cardiac signs (glucose, mg/dl, control=141±3, IBMX=210±17 P<0.001 and mc5=191±13 P<0.01) when compared to serum. In contrast, compounds from mc1, mc6, MCPIP, and Win 47203 did not significantly affect any of the subjects (control=141±3, mc1 160±7, mc6 175±9, MCPIP 179±8, and Win 47203 116±2 P>0.05). mc2 was not found to alter the umbilical cord scale (control=141±3 and mc2=145±5). When it comes to boosting cardiovascular core, IBMX is the most effective [3]. While apocynin and IBMX treatment did not significantly lower cold exposure in the right ventricle (RV), they did considerably minimize the cold-induced increase in systolic blood pressure (23.5 ± 1.8 and 24.2 ± 0.6 mmHg, respectively). The lumen diameter increases to 62.7 ± 4.2 and 59.5 ± 4.3 μM, respectively, while the thickness of the PA medial layer is 19.0 ± 0.9 and 16.9 ± 0.8 μM, respectively] [4].
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Enzyme Assay |
Measurement of cAMP content in single CCDs.[2]
Multiple individual CCDs were microdissected from a single kidney in cold Ringer solution within 1 h of euthanization of the rat, and total lengths of ∼10 mm were transferred to a 1.5-ml microcentrifuge tube to generate a single sample. Thereafter, fresh Ringer solution (50 μl) was added to each tube, and samples were allowed to equilibrate to room temperature for 5 min. Next, samples were centrifuged, the supernatant was removed, and Ringer solution (50 μl) with IBMX (100 μM) or vehicle (DMSO) alone was added. After incubation at room temperature for 20 min, samples were centrifuged, and the supernatant was stored at −80°C. For measurements of extracellular cAMP, samples of the supernatant were boiled 5 min at 95°C and then centrifuged, and 45 μl of the supernatant were mixed with 5 μl of the internal standard solution and then subjected to direct analysis. To extract intracellular cAMP from CCDs, 0.5 ml of ice-cold 1-propanol was added to the tissue pellet, and samples were placed in the cold room at 4°C on a shaker for 2 h; 1-propanol extracts were stored at −80°C. For analysis of intracellular cAMP, 1-propanol samples were taken to dryness, reconstituted in 100 μl pure water, and then centrifuged at 8,000 rpm for 10 min. Samples (90 μl) were mixed with 10 μl of internal standard solution, and this was subjected to direct analysis. cAMP measurements were performed by HPLC-tandem mass spectrometry using a triple quadrupole mass spectrometery as previously described in detail (37, 38). For each sample, total CCD cAMP content was calculated as the sum of the cAMP content measured in the extracts of single tubules plus that detected in the supernatant normalized to tubule length (in mm). |
Cell Assay |
Cells are grown in 24-well plates 105 cells per well. At confluence, monolayer cells are washed with phosphate buffer solution (PBS) and then incubated with KMUP-1 (0.1-100 μM) in the presence of 100 μM IBMX for 20 min. Incubation is terminated by the addition of 10% trichloroacetic acid (TCA). Cell suspensions are sonicated and then centrifuged at 2500× g for 15 min at 4°C. To remove TCA, the supernatants are extracted three times with 5 volumes of water-saturated diethyl ether. Then, the supernatants are lyophilized and the cyclic GMP or AMP of each sample is determined by using commercially available radioimmunoassay kits[2].
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Animal Protocol |
Mice[3]
Male mice (25-35 gram) were used in the experiment. The test compounds (IBMX, MCPIP, mc1, mc2, mc5 or mc6) or solvent (control) were injected subcutaneously to mice at 1 mg/kg dosage twice a day (8:00 a.m. and 8:00 p.m.) for 7 days. Rats[4] Six groups of male Sprague-Dawley rats were used (150-180g, 6 rats/group). Three groups of rats are exposed to a climate-controlled walk-in chamber maintained at moderate cold (5.0±1°C). The remaining groups are kept in an identical chamber maintained at room temperature (23.5±1°C, warm) and served as controls. After eight weeks of exposure to cold, 3 groups in each temperature condition received continuous IV infusion of IBMX (PDE-1 inhibitor, 8.5 mg/kg/day), Apocynin (NADPH oxidase inhibitor, 25 mg/kg/day) and vehicle (DMSO, 50%), respectively. The doses of drugs have been validated for effective inhibition of PDE-1 and NADPH oxidase activity, respectively. Body weight is measured weekly. After one week of drug infusion, the animals’ right ventricular systolic blood pressure (RVBP) is measured under anesthesia. The RVP is a reliable indicator of pulmonary arterial blood pressure (PAP) and has been used by numerous investigators for evaluating PH. |
References |
[1]. Wu BN, et al. KMUP-1, a xanthine derivative, induces relaxation of guinea-pig isolated trachea: the role of the epithelium, cyclic nucleotides and K+ channels. Br J Pharmacol. 2004 Aug;142(7):1105-14
[2]. Wei Y, et al. Angiotensin II type 2 receptor regulates ROMK-like K+ channel activity in the renal cortical collecting duct during high dietary K+ adaptation. Am J Physiol Renal Physiol. 2014 Oct 1;307(7):F833-43 [3]. Hosseini A, et al. Differential metabolic effects of novel cilostamide analogs, methyl carbostiryl derivatives, on mouse and hyperglycemic rat. Iran J Basic Med Sci. 2012 Jul;15(4):916-25. [4]. Crosswhite P, et al. Inhibition of phosphodiesterase-1 attenuates cold-induced pulmonary hypertension. Hypertension. 2013 Mar;61(3):585-92 |
Molecular Formula |
C10H14N4O2
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Molecular Weight |
222.25
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Exact Mass |
222.11167
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Elemental Analysis |
C, 54.04; H, 6.35; N, 25.21; O, 14.40
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CAS # |
28822-58-4
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Related CAS # |
IBMX;28822-58-4
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Appearance |
White to light yellow sosild
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LogP |
1.24
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tPSA |
72.68
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SMILES |
O=C(N1C)N(CC(C)C)C2=C(NC=N2)C1=O
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InChi Key |
APIXJSLKIYYUKG-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C10H14N4O2/c1-6(2)4-14-8-7(11-5-12-8)9(15)13(3)10(14)16/h5-6H,4H2,1-3H3,(H,11,12)
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Chemical Name |
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Synonyms |
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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 |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (7.51 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 16.7 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: 1.67 mg/mL (7.51 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), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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. View More
Solubility in Formulation 3: ≥ 1.67 mg/mL (7.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 0.71 mg/mL (3.19 mM) (saturation unknown) in 10% EtOH + 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 7.1 mg/mL clear EtOH stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 5: ≥ 0.71 mg/mL (3.19 mM) (saturation unknown) in 10% EtOH + 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 7.1 mg/mL clear EtOH 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. Solubility in Formulation 6: ≥ 0.71 mg/mL (3.19 mM) (saturation unknown) in 10% EtOH + 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 7.1 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 4.4994 mL | 22.4972 mL | 44.9944 mL | |
5 mM | 0.8999 mL | 4.4994 mL | 8.9989 mL | |
10 mM | 0.4499 mL | 2.2497 mL | 4.4994 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.
The stimulatory effect of ANG II on ROMK channel activity in HK-fed rats is mediated by phosphodiesterases (PDEs).Am J Physiol Renal Physiol.2014 Oct 1;307(7):F833-43 |
Total cAMP content in single CCDs of HK-fed rats is increased after IBMX treatment.Am J Physiol Renal Physiol.2014 Oct 1;307(7):F833-43 td> |