PDE10
PDE10A (phosphodiesterase 10A) is a dual-substrate phosphodiesterase that hydrolyzes both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby regulating intracellular cyclic nucleotide signaling in neurons[1][2]. The enzyme is highly enriched in striatal medium spiny neurons and functions as a key regulator of signal integration downstream of dopaminergic and glutamatergic neurotransmission within basal ganglia circuits[2][3]. Mechanistically, PDE10A controls cAMP/PKA-dependent signaling and modulates phosphorylation events associated with neuronal responsiveness, corticostriatal transmission, and striatal output pathways[3]. In experimental systems, inhibition of PDE10A elevates cyclic nucleotide signaling in both striatonigral and striatopallidal neurons, influencing dopamine D1- and D2-receptor-associated signaling networks[3]. Disease relevance has been established primarily in neuropsychiatric and neurodegenerative disorders involving striatal dysfunction, including schizophrenia and Huntington’s disease, where altered PDE10A signaling has been linked to abnormalities in corticostriatal function and neuronal activity[4][5]. Compared with other phosphodiesterase isoforms such as PDE4, PDE10A exhibits a distinctive expression pattern concentrated in medium spiny neurons and predominantly regulates cyclic nucleotide signaling within these cells rather than at dopaminergic terminals[3]. For experimental applications, selective PDE10A inhibitors have been widely used to investigate striatal signaling, basal ganglia circuitry, and cyclic nucleotide-dependent mechanisms, making PDE10A a valuable molecular target for mechanistic neuroscience research[3][4].
References:
- [1]. Sciencedirect.topics.
- [2]. Russwurm C, et al. Phosphodiesterase 10A Is Tethered to a Synaptic Signaling Complex in Striatum. J Biol Chem. 2015 May 8;290(19):11936-47. [Content Brief]
- [3]. Nishi A, et al. Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neurosci. 2008 Oct 15;28(42):10460-71. [Content Brief]
- [4]. Beaumont V, et al. Phosphodiesterase 10A Inhibition Improves Cortico-Basal Ganglia Function in Huntington's Disease Models. Neuron. 2016 Dec 21;92(6):1220-1237. [Content Brief]
- [5]. Menniti FS, et al. PDE10A Inhibitors-Clinical Failure or Window Into Antipsychotic Drug Action? Front Neurosci. 2021 Jan 20;14:600178. [Content Brief]
All Product Categories
-
PDE10 Related Products (53)
Related Products (53)
-
PDE2A-IN-3
0 ImagesPDE2A-IN-3 (Example Ic1) is a selective phosphodiesterase 2A (PDE2A) inhibitor with IC50s of 69 nM and 1762 nM for PDE2A and PDE10, respectively. PDE2A-IN-3 can be used for the study of neurological and psychiatric disorders.
-
THPP-1
0 ImagesTHPP-1, a SGC chemical probe, is a potent and orally bioavailable phosphodiesterase 10A (PDE10A) inhibitor, with Ki values of 1 nM and 1.3 nM for human and rat PDE10A, respectively. THPP-1 has excellent pharmacokinetic properties in preclinical species.
-
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.
-
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.
-
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.
-
MT-3014
0 ImagesCat. No.: HY-128349CAS No.: 1332727-40-8MT-3014 is a potent, highly selective and brain-penetrated phosphodiesterase 10A (PDE 10A) inhibitor, with IC50s of 0.062 nM and 0.09 nM for human PDE 10A and bovine PDE 10A, respectively.
-
Sp-cAMPS triethylamine
0 ImagesCat. No.: HY-110005CAS No.: 93602-66-5Sp-cAMPS triethylamine, a cAMP analog, is potent activator of cAMP-dependent PKA I and PKA II. Sp-cAMPS triethylamine is also a potent, competitive phosphodiesterase (PDE3A) inhibitor with a Ki of 47.6 µM. Sp-cAMPS triethylamine binds the PDE10 GAF domain with an EC50 of 40 μM.
-
PDE10A-IN-5
0 ImagesCat. No.: HY-173360PDE10A-IN-5 (Compound A30) is an inhibitor of phosphodiesterase 10A (PDE10A) with oral activity, and its IC50 value is 3.5 nM. PDE10A-IN-5 exerts the activity of inhibiting pulmonary vascular remodeling by inhibiting PDE10A and activating the cyclic adenosine monophosphate (cAMP)-associated signaling pathway, and can be used for research in the field of pulmonary arterial hypertension.
-
Gemlapodect
0 ImagesCat. No.: HY-152838CAS No.: 1380329-87-2Synonyms: RO554965Gemlapodect (RO554965) is an inhibitor of phosphodiesterase 10A (PDE10A). Gemlapodect can be used for researching schizophrenia.
-
(1R,2R)-Elpipodect
0 ImagesCat. No.: HY-153093ACAS No.: 1424378-99-3Synonyms: (1R,2R)-MK-8189(1R,2R)-Elpipodect ((1R,2R)-MK-8189) is the (1R,2R) enantiomer of Elpipodect (HY-153093). Elpipodect (MK-8189) is an orally active and selective PDE10A inhibitor with a Ki of 29 pM. Elpipodect can be used in research of schizophrenia.
-
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.
-
PDE4-IN-12
0 ImagesCat. No.: HY-151174CAS No.: 2901084-32-8
-
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.
-
ASP9436
0 ImagesCat. No.: HY-120291CAS No.: 1401807-89-3ASP9436 is an orally active and blood-brain barrier permeable PDE10A inhibitor with an IC50 of 8 nM against human PDE10A. ASP9436 attenuates locomotor activity in mouse hyperactivity models and ameliorates visual recognition memory impairment in neonatal mice. ASP9436 is applicable to research related to schizophrenia.
-
PDE/TRPA1/CHIT1-IN-1
0 ImagesCat. No.: HY-179503PDE/TRPA1/CHIT1-IN-1 is a phosphodiesterases (PDEs), TRPA1, and hCHIT1 (KD of 37.7 μM) inhibitor. PDE/TRPA1/CHIT1-IN-1 is a broad-spectrum PDE inhibitor, potently targeting key isoforms including PDE4B, PDE7A, PDE3A, and PDE8A with IC50s of 15.54, 15.15, 8.39 and 16.46 μM. PDE/TRPA1/CHIT1-IN-1 suppresses NLRP3 inflammasome activation and inhibits NF-κB phosphorylation, downregulating the expression of pro-inflammatory genes (TNF-α and IL-6) in vivo. PDE/TRPA1/CHIT1-IN-1 can be used for chronic obstructive pulmonary disease (COPD) and related inflammatory lung disorders research.
-
PDE10A-IN-1
0 ImagesCat. No.: HY-120945CAS No.: 1354404-30-0PDE10A-IN-1 is a phosphodiesterase 10A (PDE10A) inhibitor with an IC50 of 250 nM and the ability to cross the blood-brain barrier. PDE10A-IN-1 can be used in research on neurological disorders such as schizophrenia.
-
BJH-86
0 ImagesCat. No.: HY-178987CAS No.: 3067849-10-6BJH-86 is a soluble mitochondrial complex 1 inhibitor (oxygen consumption rate inhibition IC50 = 5 μM). BJH-86 exhibits weak inhibitory activity against phosphodiesterase 10A (PDE10A) (IC50 >10 μM). BJH-86 can reduce cellular oxygen consumption and inhibit cancer cell proliferation. BJH-86 can be used for the research of cancer, such as lung cancer.
-
Phosphodiesterase-IN-2
0 ImagesCat. No.: HY-161663CAS No.: 3047610-96-5Phosphodiesterase-IN-2 (Compound C7) is a selective, orally active inhibitor for phosphodiesterase 10A (PDE10A), with an IC50 of 11.9 nM. Phosphodiesterase-IN-2 improves the stability of liver microsomes, and lowers BBB permeability. Phosphodiesterase-IN-2 exhibits good pharmacokinetic characters, and attenuates isoprenaline (HY-108353)-induced cardiac hypertrophic in mouse models.
-
Phosphodiesterase-IN-5
0 ImagesCat. No.: HY-179645Phosphodiesterase-IN-5 is a potent, orally active and selective phosphodiesterase 10A (PDE10A) inhibitor with an IC50 of 6.2 nM. Phosphodiesterase-IN-5 shows >1612-fold selectivity over other PDEs. Phosphodiesterase-IN-5 exhibits potent antifibrotic efficacy in a Bleomycin (BLM) (HY-108345)-induced murine model of pulmonary fibrosis (PF) by blocking myofibroblast differentiation via the cAMP/PKA/CREB signaling pathway. Phosphodiesterase-IN-5 can be used for the research of PF.
