PDE10A Antibodies

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A)

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.

May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. .

Gene Information

Human
Gene Name:	PDE10A
Uniprot:	Q9Y233
Entrez:	10846

Family

Belongs to:
cyclic nucleotide phosphodiesterase family

Alternative Names

cAMP and cAMP-inhibited cGMP 3'-5'-cyclic phosphodiesterase 10A; dJ416F21.1 (phosphodiesterase 10A); EC 3.1.4; EC 3.1.4.17; EC 3.1.4.35; FLJ11894; FLJ25677; HSPDE10A; phosphodiesterase 10A; phosphodiesterase 10A1 (PDE10A1)

Molecular Weight

Mass (kDA):
88.412 kDA

Genomic Context

Human
Location:	6q27
Sequence:	6; NC_000006.12 (165327287..165988115, complement)

Tissue Specificity

Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum.

Subcellular Localizations

Cytoplasm. Located mostly to soluble cellular fractions.

Diseases

• Schizophrenia
• Mental Disorders
• Huntington Disease
• Psychotic Disorders
• Pcp - Hallucinogen-related Disorder
• Anxiety Disorders
• Globus Hystericus
• Impaired Cognition
• Bipolar Disorder
• Nervousness
• Hypokinesia
• Neurobehavioral Manifestations
• Impairment (finding)

• Depressive Disorder
• Catalepsy
• Nervous System Disorder
• Down Syndrome
• Insulinoma
• Parkinson Disease
• Asthma

Pathways

• Localization
• Cognition
• Secretion
• Insulin Secretion
• Transport
• Prepulse Inhibition
• Locomotion
• Cell Adhesion
• Proteolysis
• Lung Development
• Hypersensitivity
• Cardiac Conduction
• Reflex

• Operant Conditioning
• Reverse Transcription
• Axon Guidance
• Lung Morphogenesis
• Hormone Secretion
• Righting Reflex
• Associative Learning

PTMs

• Phosphorylation

• Cleavage

• Palmitoylation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/PDE10A

Best Uses Of The PDE10A Marker

Many people have heard of the significance and importance of the PDE10A gene. Its expression in the body is essential for many physiological processes, including the production of hormones. There are a few biomarkers that can help us identify potential drug candidates. One of these markers is the gene PDE10A, which is present in the human and rat tissues. This gene can also be used to predict the binding affinity and activity of the related analogues and also their selectivity and activity.

Predicting the binding affinity of similar analogs

In the present study, we used a model of irreversible PDE inhibitors built on nucleophilic residues within the binding pocket. These residues were identified using structural and sequence alignment respectively. The binding pocket of similar analogues was used to determine the position of residues that were likely nucleophilic within PDE10A.

We found that the cAMP binding to TcrPDEB1 was 0.97 moles/mol protein. In contrast, the GAF-A domains of other PDEs connect to cAMP using a homostoichiometry of 0.5 mg/mol. These data suggest that TcrPDEB1 binds to CAMP with less affinity then TcrPDEB2.

The PDE4A complex was docked to the crystal structure of a similar ligand known as PTXm-5. We carried out MD simulations to predict the binding affinity of both ligands and PDEs and then calculated the energy of binding. The observed changes were not significant, which suggests that PTXm-5 interacts with PDE10A within the same binding pocket.

PTX binds with PDE4A, PDE4D and PDE10A. The molar dissociation constant of PTX was 306 uM and its DG was 4.79 kcal/mol at 298K. This marker is extremely specific and can be used to accurately determine the binding affinity of related analogues.

Similarly to that, a PET radioligand for PDE10A was examined. It showed high binding affinity to human PDE10A2 recombinant PDE10A2 and also superiority over other PDEs. Radiolabeled T-773that was radiolabeled in radiography and was selectively accumulated in the striatum. It also was selective to PDE10A within the striatum.

Current data show that Kinetoplastid PDE activities are present in lysates derived from various species. In addition, the genome of several Kinetoplasts suggest the presence four distinct Class I PDE families and at least two adenylate-cyclases. In addition to the kinetoplast PDE activity, T. cruzi encodes two members of the PDE family.

The new PDE10A marker also provides a better understanding of the binding pockets. PDE10A marker-based modeling has shown that the PDE10A marker is effective in predicting the binding affinity of the related analogs. The binding affinity of the PTXm-1 marker is even higher than that of PTX. It has lower DGbind.

Two human adenosomatid PDEs were employed as a standard, TcrPDEB1 & TcrPDEB2. We also utilized fluorescent CAMP analogs to test for TcrPDEB1 as well as TcRDEB2. This allowed us to determine the binding affinity of PDE inhibitors to the closely related trypanosome PDEs.

Biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines

Biochemical characterization and anti-proliferative activities of potent and selective 2-(3-azetidinyl)-quinolines were performed using MCAN/ES/92/BCN722 strain of L. infantum isolated from a dog with visceral leishmaniosis. The sulforhodamin B assay was used to test the anti-proliferative capacity of the compounds. In the 96-well plates, cells were exposed for a series of exposures to diluted compound solution and washed with PBS. The cells were fixed in 10% trichloroacetic acids for 1 h. The cells were then washed five times with 1% acetic acid and were analyzed for

8i inhibited the phosphorylation process and GSK2126458 of Akt and GSK2126458 respectively, and phosphorylation and Akt of the S6 ribosomal proteins at Ser235/236. The anti-phosphorylated S6 Ribosomal Protein was pSer235/236, and phos-4EBP1 at Thr37/46.

Biochemical analyses revealed that all of these quinolines inhibit the PI3K/mTOR pathway, and are extremely potent mTOR inhibitors. The study also demonstrated that two quinolines block mTOR in HCT116 cancer cells of colorectal cancer with IC50 values of 0.50 nM to 2.03 nM.

Biochemical the synthesis of benzimidoyl chlorines, the phenyl ketone and its derivatives has produced numerous quinolones. The cyclization of 1-azido-2-propynyl-benzenes with electrophilic reagents has produced diverse quinolones.

We have shown that it is possible to make powerful and specific azole-based quinolines as anticancer drugs. We also have demonstrated that these compounds are effective in the treatment of HIV. We conclude that quinolines have great potential to be useful in the future. They also reduce inflammation and can inhibit tumor growth.

They were made by mixing a mixture of LiAlH4 (aqueous NaH) to determine their efficacy and selectivity. The reaction mixture was allowed to stand for 30 min and was then supplemented with 6-bromoquinoline-4-carbaldehyde.

Biological evaluation of potent and selective 2-alkoxy-1-azetididinyl-quinolines is a necessary step before developing a new drug. This drug is able to be used in many ways and may aid in the fight against AIDS and tumors. In addition to being antimalarial, these drugs can improve central nervous system and cardiovascular functions and reduce the risk of bacterial and fungal infections.

In the quinoline family the thienoquinolines constitute a significant structural component in medicinal chemical. They have bioactive qualities, such as urea transporter inhibitory and anti-inflammatory effects. They also block platelet aggregation. They also inhibit platelet aggregation. GI50 values are below 0.5 mM.

In a stirred flask a solution of 6a, 25mmol in Methanol , and 2.5 N NaOH were made. The reaction was started after the plate was coated with the pre-heated NADPH solution. To check for residual products the stop solution was added to the plate at each interval. The supernatant was gathered for analysis by LC/MS/MS.

PTP1B was inhibited by compound 8i. It was a powerful inhibitor of PAM signaling and reduced three biomarkers for mTOR. The stability of its metabolism was acceptable, as was its long half-life in microsomes of the liver. This compound is able to be further improved. Its toxicity is unknown.

This research led to the discovery of a novel class of PDE10A inhibitors. The inhibitors, known as dihydroimidazoisoquinolines, showed a high biochemical potency and in vivo efficacy. Optimized compounds from this class also proved effective in animal models for schizophrenia, suggesting that they could be useful in treating schizophrenia.