PDE10 Inhibitor

Avanafil (TA-1790) 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 activates NO/cGMP/PKG signaling-pathway to decrease loss in BMD, bone atrophy, and oxidative stress. Avanafil inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Avanafil can be used for the research of erectile dysfunction and osteoporosis.

Mardepodect is a potent, selective orally active, and brain-penetrant PDE10A inhibitor with an IC₅₀ of 0.37 nM, with >1000-fold selectivity over other PDEs.

PF-05180999 (PF-999) is a phosphodiesterase 2A (PDE2A) inhibitor, with an IC₅₀ of 1.6 nM.

Balipodect (TAK-063) is a selective, brain-penetrant and orally active PDE10A inhibitor with an IC₅₀ of 0.30 nM. Balipodect shows >15000-fold selectivity over other PDEs. Balipodect elevates striatal cAMP and cGMP levels in mice. Balipodect can be used for the study of schizophrenia_[1].

TP-10 is a selective PDE10A inhibitor with an IC₅₀ value of 0.8 nM. TP-10 shows an antioxidant activity with IC₅₀s of 31.72 and 16.04 μg/ml for DPPH and CUPRAC, respectively. TP-10 can be used for the research of neuropathy.

Alofropodect is an orally active, blood-brain barrier permeable phosphodiesterase 10A (PDE10A) inhibitor with IC₅₀ values of 1 nM (Reference 1) and 35 nM (Reference 2). Alofropodect acts as a negative allosteric modulator of the M2 muscarinic receptor with an IC₅₀ of 9.2 μM. Alofropodect alters cyclic nucleotide levels in basal ganglia circuits, inhibits the hydrolysis of cAMP and cGMP, and suppresses hERG potassium channel tail currents. Alofropodect induces catalepsy in rats and reverses injury-induced contralateral forelimb use impairment. Alofropodect can be used in research related to schizophrenia, Parkinson's disease, and levodopa-induced dyskinesia.

Multitarget 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 K_d 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.

Elpipodect (MK-8189) is an orally active and selective PDE10A inhibitor with a K_i value of 29 pM. Elpipodect can be used in research of schizophrenia.

BC11-38 is a potent, selective, and biologically active PDE11 inhibitor, with IC₅₀s of 0.28 µM and >100 µM for PDE11 and PDE1-10, respectively. BC11-38 elevates cAMP levels, PKA-mediated ATF-1 phosphorylation, and cortisol production in H295R cells.

Naperiglipron (LY3549492) is an orally active Glucagon-like peptide 1 receptor (GLP-1R) agonist with an EC₅₀ of 1.14 nM for hGLP-1R. Naperiglipron significantly decreases the level of blood glucose in GLP-1R knock-in mouse models. Naperiglipron inhibits PDE10A1 enzyme activity (IC₅₀: 7.43 μM) with a weak hERG inhibitory activity. Naperiglipron can be used for type II diabetes mellitus (T2DM) and obesity research.

Sp-cAMPS sodium salt, a cAMP analog, is potent activator of cAMP-dependent PKA I and PKA II. Sp-cAMPS sodium salt is also a potent, competitive phosphodiesterase (PDE3A) inhibitor with a K_i of 47.6 µM. Sp-cAMPS sodium salt binds the PDE10 GAF domain with an EC₅₀ of 40 μM.

5,7-Dichloropyrazolo[1,5-a]pyrimidine is a PDE10A inhibitor with a K_i of 24 μM. 5,7-Dichloropyrazolo[1,5-a]pyrimidine serves as a key intermediate in the synthesis of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives (HIV-1 non-nucleoside reverse transcriptase inhibitors). 5,7-Dichloropyrazolo[1,5-a]pyrimidine can be used for the research of schizophrenia.

Mardepodect hydrochloride (PF-2545920 hydrochloride) is a potent, orally active and selective PDE10A inhibitor with an IC₅₀ of 0.37 nM, with >1000-fold selectivity over other PDEs. Mardepodect hydrochloride can cross the blood-brain barrier.

N-Methylbenzamide is a potent phosphodiesterase 10A (PDE10A) inhibitor. N-Methylbenzamide has anti-cancer activity.

Morcamilast (ME3183) is a potent, orally active, selective phosphodiesterase 4 (PDE4) inhibitor, with IC₅₀ values of 1.28 nM, 2.33 nM and 1.63 nM against human PDE4A1A, PDE4B1 and PDE4D2, respectively. Morcamilast inhibits the production of TNF-α, IL-12/23p40, IL-23, IL-17A, IL-4, IL-5 and IL-13 in human PBMCs and T cells, and alleviates chronic Oxazolone (HY-126360)-induced dermatitis, Substance P (HY-P0201)-induced pruritus, Imiquimod (HY-B0180)-induced psoriasis-like dermatitis and LPS (HY-D1056)-induced arthritis. Morcamilast is used for the research of psoriasis, atopic dermatitis, psoriatic arthritis and other inflammatory and immune-related diseases.

Tofisopam, a 2,3-benzodiazepine compound, is an orally active anxiolytic agent. Tofisopam can inhibit phosphodiesterase PDE isoenzyme activity, withIC₅₀ values of 2.11 μM, 1.98 μM, 0.42 μM, and 0.92 μM for PDE-2A3, PDE-3A, PDE-4A1, and PDE-10A1, respectively. Tofisopam can be used for the study of anxiety.

(S)-C33 is a potent and selective PDE9 (phosphodiesterase-9) inhibitor, with an IC₅₀ of 11 nM. (S)-C33 can be used for central nervous system diseases and diabetes research.

Sp-cAMPS, a cAMP analog, is potent activator of cAMP-dependent PKA I and PKA II. Sp-cAMPS is also a potent, competitive phosphodiesterase (PDE3A) inhibitor with a K_i of 47.6 µM. Sp-cAMPS binds the PDE10 GAF domain with an EC₅₀ of 40 μM.

PQ-10 is a potent inhibitor of Phosphodiesterase 10A (PDE10A) with IC₅₀ andED₅₀ of 4.6 nM and 13 mg/kg, respectively. PQ-10 induces patterns of brain glucose metabolism which can be a potential translational biomarker. PQ-10 has the potential for researching psychiatric disorders like schizophrenia.

PDE10A-IN-2 hydrochloride is a potent, highly selective and orally active phosphodiesterase 10A (PDE10A) inhibitor with an IC₅₀ of 2.8 nM. PDE10A-IN-2 hydrochloride shows selectivity of >3500-fold against other PDE subtypes. PDE10A-IN-2 hydrochloride can be used for pulmonary arterial hypertension (PAH) research.