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Other Inhibitors: Phosphodiesterase (PDE) Inhibitors
 | | | Classification | Selected Inhibitors | Inhibitors | Related Product
cAMP and cGMP, two important second messengers molecules are hydrolyzed by phosphodiesterases (PDEs) in the cell, leading to cessation of cAMP and cGMP-dependent effects. PDEs comprise a large group of enzymes organized into 11 distinct families based on their biochemical and molecular properties. Many of these isozymes are differently expressed and regulated in different cells and exhibit distinct selectivity for cAMP and cGMP.
PDEs contain three functional domains: a regulatory N-terminus, a central catalytic domain, and a regulatory C-terminus. All isozymes exhibit significant homology in their catalytic domain. The N- and C-terminal domains also display moderate homology within families and impart specific characteristics to different subtypes. The N-terminus is involved in allosteric regulation and membrane targeting. The C-terminus is believed to be involved in dimerization and possess docking sites for PDE-specific kinases.
Due to their involvement in inflammation, asthma, and cardiovascular complications, PDEs are considered to be attractive targets for pharmacological intervention. A number of PDE inhibitors have been developed that target specific isoenzymes, thereby increasing tissue selectivity and minimizing any side effects. | | | | Classification of Phosphodiesterases | PDE | Regulatory Mechanisms | Substrate | I | Ca2+/CaM-stimulated | Heart, brain, lung, smooth muscle | II | c-GMP-stimulated | Adrenals, heart, lung, liver, platelets | III | cGMP-inhibited | Heart, lung, liver, platelets, adipose tissue | IV | cAMP-specific | Kidney, brain, liver, lung, Sertoli cells | V | cGMP-specific | Lung, platelets, smooth muscle | VI | Photoreceptor cGMP-specific | Photoreceptors | VII
| cAMP-specific, high-affinity,
rolipram-insensitive | Skeletal muscle, heart, kidney, brain, pancreas, T cells | VIII | cAMP-selective, IBMX-insensitive | Testes, eye, liver, skeletal muscle, heart, kidney, ovary, brain, T cells | IX | cGMP-selective, IBMX-
insensitive | Kidney, liver, lung, brain | X | cGMP-sensitive | Testes, brain | XI | cGMP-sensitive, dual-specificity | Skeletal muscle, prostrate, kidney, liver, pituitary, salivary glands, testes |
| | | | Phosphodiesterase (PDE) Inhibitors | | Product | Cat. No. | MW | IC50(mM) | PDE Types Inhibited | | Calmidazolium Chloride | | 687.7 | 0.01 | I | | Chlorpromazine, HCl | | 355.3 | 17.0 | I | | Cilostamide | | 342.4 | 0.07 | III | | Denbufylline | | 320.4 | 1.0 | IV | | Dipyridamole | | 504.6 | 0.9 | V | | EHNA, HCl | | 313.8 | 0.8 | II | | Etazolate, HCl | | 325.8 | 2.0 | IV | | 3-Isobutyl-1-methylxanthine (IBMX) | | 222.2 | 2-50 | Non-selective | | 8-Methoxymethyl-3-isobutyl-1-methylxanthine | | 266.3 | 4.0 | I | | 4-{[3’,4’-(Methylenedioxy)benzyl]amino}-6-methoxyquinazoline | | 309.3 | 0.23 | V | | Milrinone | | 211.2 | 0.30 | III | | MY-5445 | | 331.8 | 0.60 | V | | Pentoxifylline | | 278.3 | | Non-selective | | Phosphodiesterase 4 Inhibitor | | 289.3 | * | IV | | Phosphodiesterase V Inhibitor II | | 403.5 | 0.005 | V | | Ro-20-1724 | | 278.4 | 2.0 | IV | | Rolipram | | 275.4 | 0.8 | IV | | Trequinsin, HCl | | 442.0 | 0.0003 | III | | Vinpocetine | | 350.5 | 20.0 | I | | Zaprinast | | 271.3 | 0.45 | V |
| | | | Inhibitors: Phosphodiesterase | |
| | | | Related Product | | Product Name | Cat. No. | Comments | | Phosphodiesterase Inhibitor Set I | | Provided as a set of 4 vials. Each set contains:
- 10 mg of 8-Methoxymethyl-3-isobutyl-1-methylxanthine (Cat. No. 454202), a Ca2+/CaM-dependent PDE (PDE I) inhibitor
- 1 mg of 4-{[3,4 -(Methylenedioxy)benzyl]amino}-6-methoxyquinazoline (Cat. No. 475250), a cGMP-specific PDE (PDE V) inhibitor
- 5 mg of Rolipram (Cat. No. 557330), a cAMP-specific PDE (PDE IV) inhibitor
- 10 mg of Trequinsin, Hydrochloride (Cat. No. 382425), a cGMP-inhibited PDE (PDE III) inhibitor
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