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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T-0156
0 ImagesCat. No.: HY-105349CAS No.: 324572-93-2T-0156 is a potent and selective phosphodiesterase type 5 (PDE5) inhibitor. T-0156 specifically inhibits the hydrolysis of cyclic guanosine monophosphate (cGMP) by PDE5 in a competitive manner (IC50=0.23 nM). T-0156 inhibits PDE6 (IC50=56 nM) and has low potencies against PDE1, PDE2, PDE3, and PDE4 (IC50>10 μM). T-0156 enhances the nitric oxide (NO)/cGMP pathway.
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PF-04822163
0 ImagesCat. No.: HY-120741CAS No.: 1798334-07-2PF-04822163 is an orally active, selective, and blood-brain barrier permeable PDE1 inhibitor with IC50 values of 2 nM, 2.4 nM, and 7 nM for PDE1A, PDE1B, and PDE1C respectively. PF-04822163 can be used in the research of attention deficit hyperactivity disorder or Parkinson's disease.
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Vardenafil dihydrochloride
0 ImagesCat. No.: HY-B0442CCAS No.: 224789-15-5Vardenafil dihydrochloride is a selective and orally active inhibitor of phosphodiesterase-5 (PDE5), with an IC50 of 0.7 nM. Vardenafil dihydrochloride shows inhibitory towards PDE1, PDE6 with IC50s of 180 nM, and 11 nM respectively, while IC50s are >1000 nM for PDE3 and PDE4. Vardenafil dihydrochloride competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Vardenafil dihydrochloride can be used for the research of erectile dysfunction, hepatitis, diabetes-.
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Avanafil dibenzenesulfonate
0 ImagesCat. No.: HY-18252ACAS No.: 330784-48-0Synonyms: TA1790 dibenzenesulfonateAvanafil (TA-1790) dibenzenesulfonate is a potent and selective phosphodiesterase-5 (PDE-5) inhibitor with IC50 values of 5.2 nM, 630 nM, 5700 nM, 6200 nM, 12000 nM, 27000 nM, 51000 nM and 53000 nM for PDE-5, PDE-6, PDE-4, PDE-10, PDE-8, PDE-7, PDE-2 and PDE-1, respectively. Avanafil dibenzenesulfonate activates NO/cGMP/PKG signaling-pathway to decrease loss in BMD, bone atrophy, and oxidative stress. Avanafil dibenzenesulfonate inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Avanafil dibenzenesulfonate can be used for the research of erectile dysfunction and osteoporosis.
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TPN729MA
0 ImagesSynonyms: TPN729 maleateTPN729MA (TPN729 maleate) is a selective phosphodiesterase type 5 (PDE5) inhibitor with an IC50 value of 2.28 nM. TPN729MA affects erectile function and it can be used for the research of erectile dysfunction.
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TPN729
0 ImagesCat. No.: HY-116808CAS No.: 936951-20-1TPN729 is a selective phosphodiesterase type 5 (PDE5) inhibitor with an IC50 value of 2.28 nM. TPN729 affects erectile function and it can be used for the research of erectile dysfunction.
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PDE5-IN-2
0 ImagesCat. No.: HY-112704CAS No.: 2244517-61-9PDE5-IN-2 is a potent, highly selective, and orally active PDE5 inhibitor, with an IC50 of 0.31 nM, less potently inhibits PDE2A, PDE10A, PDE4D2, and PDE6C, with IC50s of 106, 46, 43, 1.2 nM, respectively. Anti-pulmonary arterial hypertension activity.
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ID11916
0 ImagesCat. No.: HY-173640CAS No.: 2785317-21-5ID11916 is an orally active androgen receptor (AR) antagonist and a phosphodiesterase 5 (PDE5) inhibitor. ID11916 blocks androgen binding to AR, nuclear translocation, and androgen-dependent transcriptional activity of AR, while increasing intracellular cGMP levels and activating PKG via inhibition. ID11916 shows potent anti-cancer effect in prostate cancer cell lines VCaP and 22Rv1 and in AR-positive breast cancer cell lines SK-BR-3.
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OPC 33540
0 ImagesCat. No.: HY-112631CAS No.: 189362-27-4OPC-33540 is a highly selective and competitive PDE3 inhibitor with IC50 values of 0.32 nM (PDE3A) and 1.5 nM (PDE3B). OPC-33540 exhibits IC50s against PDE1, PDE2, PDE4, PDE5, and PDE7 of 42.9, 52.3, 100.8, 2.5, and 51.3 μM, respectively. OPC-33540 significantly enhances cAMP accumulation in platelets and effectively inhibits thrombin-induced platelet aggregation. OPC-33540 can be used in antithrombotic studies.
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Thioquinapiperifil
0 ImagesCat. No.: HY-119611CAS No.: 220060-39-9Synonyms: KF31327 free baseThioquinapiperifil (KF31327 free base), a potent, selective and non-competitive phosphodiesterase-5 (PDE-5, IC50 of 0.074 nM) inhibitor, is used for sexual enhancement study.
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T-1032 free base
0 ImagesCat. No.: HY-W705784CAS No.: 212500-02-2T-1032 free base is a selective phosphodiesterase 5 (PDE5) inhibitor with an IC50 value of 1.0 nM. T-1032 free base shows relaxant effect on isolated rabbit corpus cavernosum. T-1032 free base can be used for the research of erectile dysfunction.
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PDE5-IN-3
0 ImagesCat. No.: HY-131710CAS No.: 2538149-57-2PDE5-IN-3 (compound 11j) is a potent PDE5 inhibitor with an IC50 of 1.57 nM. PDE5-IN-3 shows moderate EGFR inhibition with IC50 of 5.827 µM. PDE5-IN-3 significantly inhibits the Wnt/β-catenin pathway (IC50=1286.96 ng/mL). PDE5-IN-3 induces the intrinsic apoptotic mitochondrial pathway in HepG2 cells. PDE5-IN-3 has strong antitumor activity.
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PDE5-IN-13
0 ImagesCat. No.: HY-170435PDE5-IN-13 (Compound 14b) inhibits phosphodiesterase 5 (PDE5A) with an IC50 of 3 nM. PDE5-IN-13 is a potential candidate for PAH (pulmonary arterial hypertension) research. PDE5-IN-13 has high selectivity for targets over PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11. PDE5-IN-13 is orally active.
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(R)-Xanthoanthrafil
0 ImagesCat. No.: HY-136520ACAS No.: 247568-68-9(R)-Xanthoanthrafil is a phosphodiesterase-5 (PDE5) inhibitor. (R)-Xanthoanthrafil selectively inhibits PDE5, increasing cyclic guanosine monophosphate (cGMP) levels, leading to smooth muscle relaxation and promoting penile erection. (R)-Xanthoanthrafil can be used to study erectile dysfunction.
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BMS-341400
0 ImagesCat. No.: HY-107022CAS No.: 296250-53-8BMS-341400 is an orally active selective phosphodiesterase 5 (PDE5) inhibitor with an IC50 value of 0.3 nM. BMS-341400 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 can be used to study erectile dysfunction.
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PF-03049423 free base
0 ImagesPF-03049423 (Compound PF-5) free base 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 free base can be used for the research of acute ischaemic stroke.
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PDE4-IN-12
0 ImagesCat. No.: HY-151174CAS No.: 2901084-32-8
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Multitarget AD-IN-6
0 ImagesCat. No.: HY-181762Multitarget AD-IN-6 (Compound 39) is a multi-target inhibitor, with an IC50 of 15.54 μM against PDE4B, 15.15 μM against PDE7A, 8.39 μM against PDE3A, and a Kd of 37.7 μM against CHIT1. Multitarget AD-IN-6 acts as a TRPA1 antagonist, reduces the level of the NLRP3 inflammasome multiprotein complex to inhibit its activation, while inhibiting PDE4B, PDE7A and CHIT1, and decreasing the phosphorylation of NF-κB. Multitarget AD-IN-6 improves the pathology of elastase-induced emphysema in mice. Multitarget AD-IN-6 is applicable for the research of chronic obstructive pulmonary disease.
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CM-545
0 ImagesCat. No.: HY-119316ACAS No.: 1624792-70-6
