PDE5
PDE5 is a cGMP-specific phosphodiesterase that hydrolyzes cGMP and functions as a dimeric multidomain enzyme[1]. Mechanistically, cGMP generated through nitric oxide-soluble guanylyl cyclase signaling provides the main substrate context for PDE5-dependent signal termination[1]. PDE5 activity is further regulated by cGMP binding to the GAF A domain and by phosphorylation in smooth muscle cells[2][3]. Compared with broader PDE families, PDE5 belongs to the cGMP-selective group, whereas PDE1, PDE2, PDE3, PDE10, and PDE11 hydrolyze both cAMP and cGMP[4]. The PDE5A gene encodes PDE5, and human penile cavernosum studies identified PDE5A1, PDE5A2, and PDE5A3 isoforms[5][6]. In disease-relevant studies, sildenafil improved exercise capacity, WHO functional class, and hemodynamics in symptomatic pulmonary arterial hypertension[7]. For experimental and translational applications, PDE5 inhibitors support research on erectile dysfunction, pulmonary arterial hypertension, lower urinary tract symptoms, and NO/cGMP pathway pharmacology[8][9]. GAF-domain biosensor work also supports PDE5-based tools for identifying compounds that modulate cGMP binding and catalytic regulation[10].
References:
- [1]. Ahmed WS, et al. Phosphodiesterase 5 (PDE5): Structure-function regulation and therapeutic applications of inhibitors. Biomed Pharmacother. 2021 Feb;134:111128. [Content Brief]
- [2]. Rybalkin SD, et al. PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. EMBO J. 2003 Feb 3;22(3):469-78. [Content Brief]
- [3]. Rybalkin SD, et al. Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem. 2002 Feb 1;277(5):3310-7. [Content Brief]
- [4]. Maurice DH, et al. Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov. 2014 Apr;13(4):290-314. [Content Brief]
- [5]. Kass DA, et al. Phosphodiesterase type 5: expanding roles in cardiovascular regulation. Circ Res. 2007 Nov 26;101(11):1084-95. [Content Brief]
- [6]. Lin CS, et al. Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. Biochem Biophys Res Commun. 2000 Feb 16;268(2):628-35. [Content Brief]
- [7]. Galiè N, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005 Nov 17;353(20):2148-57. [Content Brief]
- [8]. Andersson KE. PDE5 inhibitors - pharmacology and clinical applications 20 years after sildenafil discovery. Br J Pharmacol. 2018 Jul;175(13):2554-2565. doi: 10.1111/bph.14205. Epub 2018 Apr 25. PMID: 29667180; PMCID: PMC6003652. et al. PDE5 inhibitors - pharmacology and clinical applications 20 years after sildenafil discovery. Br J Pharmacol. 2018 Jul;175(13):2554-2565. [Content Brief]
- [9]. Yuan J, et al. Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction: a systematic review and network meta-analysis. Eur Urol. 2013 May;63(5):902-12. [Content Brief]
- [10]. Biswas KH, et al. The GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) is a sensor and a sink for cGMP. Biochemistry. 2008 Mar 18;47(11):3534-43. [Content Brief]
All Product Categories
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PDE5 Related Products (97)
Related Products (97)
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PDE5-IN-5
0 ImagesCat. No.: HY-147990CAS No.: 2414921-33-6PDE5-IN-5 (Compound 11) is a potent, selective phosphodiesterase 5 (PDE5) inhibitor with an IC50 of 2.0 nM.
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PF-03049423
0 ImagesCat. No.: HY-10679ACAS No.: 402955-58-2PF-03049423 (Compound PF-5) is a potent and highly selective phosphodiesterase-5A inhibitor with an IC50 of about 0.2 nM for rat and human platelet enzyme. PF-03049423 can be used for the research of acute ischaemic stroke.
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PDE4/5-IN-1
0 ImagesCat. No.: HY-181774CAS No.: 1807631-43-1PDE4/5-IN-1 is a selective phosphodiesterase 4/5 (PDE4/5) dual inhibitor. PDE4/5-IN-1 functionally inhibits PDE5, PDE4B2, and PDE4D2 activity. PDE4/5-IN-1 relaxes isolated rat prostate tissue, enhances nitric oxide-induced relaxation in isolated rat prostate tissue, and reduces alpha-1 adrenoceptor-mediated contractile responses in isolated rat prostate tissue. PDE4/5-IN-1 inhibits proliferation of human hyperplastic prostate cells. PDE4/5-IN-1 can be used for the research of benign prostatic hyperplasia.
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PDE1-IN-4
0 ImagesCat. No.: HY-147946CAS No.: 3031349-98-8PDE1-IN-4 (compound 2g) is a potent and selective PDE1 (phosphodiesterase-1) inhibitor, with IC50 values of 10, 145, and 354 nM for PDE1C, PDE1A, and PDE1B, respectively. PDE1-IN-4 inhibits myofibroblast differentiation of human lung fibroblasts induced by TGF-β1. PDE1-IN-4 shows anti-fibrosis effects through the regulation of cAMP (3′,5′-cyclic adenosine monophosphate) and cGMP (3′,5′-cyclic guanosine monophosphate). PDE1-IN-4 can be used for idiopathic pulmonary fibrosis (IPF) research.
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Girisopam
0 ImagesCat. No.: HY-187129CAS No.: 82230-53-3Girisopam is a PDE inhibitor with IC50 values of 3.2, 4.0, and 12.5 μM against PDE4, PDE2, and PDE5, respectively. Girisopam exhibits anxiolytic, antidepressant, anti-aggressive, and antipsychotic activities. The binding sites of Girisopam are enriched exclusively in the basal ganglia of rat brains, and depletion of these sites is associated with damage to the striatonigral pathway. Girisopam enhances the potency of μ-opioid receptor agonists, attenuates the antagonistic effect of low-dose Naloxone (HY-17417A), and synergistically potentiates the anti-fighting effect of Chlorpromazine (HY-12708). Girisopam can be used in studies related to psychiatric disorders such as anxiety and depression.
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BL-122
0 ImagesCat. No.: HY-114218CAS No.: 1220393-12-3BL-122 is a selective phosphodiesterase-5 (PDE-5) inhibitor. BL-122 can increase the level of cGMP in the tissue, promote the expression of nitric oxide (NO), and mediate the relaxation of smooth muscle. BL-122 can be used for the researches of inflammation, immunology and cardiovascular disease, such as asthma and hypertension.
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UK 343664
0 ImagesCat. No.: HY-105341CAS No.: 215297-27-1UK 343664 is a potent, orally active and selective PDE5 inhibitor. UK 343664 partially reverses Thromboxane-induced pulmonary hypertension.
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N-Desethyl-N-methyl vardenafil
0 ImagesCat. No.: HY-W715511CAS No.: 224785-87-9Synonyms: Demethyl-vardenafilN-Desethyl-N-methyl vardenafil (Demethyl-vardenafil), an analog of Vardenafil (HY-B0442), is a PDE5 inhibitor with an IC50 value of 0.14 μM.
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Xanthoanthrafil
0 ImagesCat. No.: HY-136520BCAS No.: 1020251-53-9Xanthoanthrafil is a potent phosphodiesterase-5 (PDE5) inhibitor, with an IC50 of 3.95 ng/mL. Xanthoanthrafil can be used for the research of erectile dysfunction.
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SCH 51866
0 ImagesCat. No.: HY-116262CAS No.: 167298-74-0SCH 51866 is a potent, selective and orally active inhibitor of PDE1 (IC50=70 nM) and PDE5 (IC50=60 nM). SCH 51866 inhibits collagen-induced aggregation of human washed platelets (IC50=10 μM), prevents neointimal formation in balloon catheter-injured carotid arteries of spontaneously hypertensive rats (SHR), and reduces blood pressure in SHR. SCH 51866 can be used in the study of hypertension.
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UK-371800
0 ImagesCat. No.: HY-19446CAS No.: 247582-13-4UK-371800 is a highly selective PDE5 inhibitor (IC50 = 4.2 nM). UK-371800 has good permeability and is not affected by the efflux of P-glycoprotein.
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UK 357903
0 ImagesCat. No.: HY-19420CAS No.: 247580-98-9UK 357903 is a selective inhibitor for phosphodiesterase 5 (PDE5), with IC50s of 1.7 and 714 nM, for PDE5 and PDE6. UK 357903 exhibits vasodilatory effects on the mesenteric and hindlimb vascular beds, and is potential for ameliorating erectile dysfunction.
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JNJ-10258859
0 ImagesCat. No.: HY-123145CAS No.: 374927-03-4JNJ-10258859 is a potent and selective phosphodiesterase type 5 inhibitor, with a Ki of 0.23 nM. JNJ-10258859 can be used for erectile dysfunction research.
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BMS-341400 mesylate
0 ImagesCat. No.: HY-107022ACAS No.: 296250-54-9BMS-341400 mesylate is a selective phosphodiesterase 5 (PDE5) inhibitor with an IC50 value of 0.3 nM. BMS-341400 mesylate reduces the degradation of cyclic guanosine monophosphate (cGMP), thereby enhancing nitric oxide (NO)-mediated relaxation of the smooth muscle of the corpus cavernosum and promoting erection. BMS-341400 mesylate can be used to study erectile dysfunction.
