Tovinontrine (IMR-687) is a highly potent and selective phosphodiesterase-9 (PDE9) inhibitor specifically for the treatment of sickle cell disease. IC50s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively[1].
NPD-001 is a potent Trypanosoma brucei phosphodiesterases TbrPDEB1 and TbrPDEB2 inhibitor, with IC50 values of 4 and 3 nM, respectively. NPD-001 also inhibits human PDEs (phosphodiesterases). NPD-001 shows good anti trypanosomal activity, with an IC50 of 80 nM[1].
PDEδ-IN-99 is a novel potent K-Ras-PDEδ inhibitor that binds to the farnesyl binding pocket of PDEδ with Kd of 8±4 nM.
BI 1015550 is an orally active inhibitor of PDE4B with an IC50 value of 7.2 nM. BI 1015550 has good safety and potential applications in inflammation, allergic diseases, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD)[1][2].
ATX inhibitor 1 is a potent ATX (IC50=1.23 nM, FS-3 and 2.18 nM, bis-pNPP) inhibitor.
cis-ent-Tadalafil (Tadalafil EP Impurity C) is a highly potent PDE5 inhibitor with an IC50 value of 5 nM and has blood pressure lowering activity[1].
CALP1 is a calmodulin (CaM) agonist (Kd of 88 µM) with binding to the CaM EF-hand/Ca2+-binding site. CALP1 blocks calcium influx and apoptosis (IC50 of 44.78 µM) through inhibition of calcium channel opening. CALP1 blocks glutamate receptor channels and blocks a store-operated nonselective cation channel. CALP1 activates CaM-dependent phosphodiesterase activity[1][2][3][4].
5,7-Diacetoxy-8-methoxyflavone is a natural product that could come from scutellaria genus plants. 5,7-Diacetoxy-8-methoxyflavone has inhibitory activity for cAMP phosphodiesterase[1].
cis-Tadalafil is a PDE5 inhibitor (IC50: 0.09 μM). cis-Tadalafil can be used for research of cardiovascular diseases[1].
1,3,5-Trihydroxy-4-prenylxanthone is a Na+/H+ exchange system (Na+/H+ Exchanger (NHE)) inhibitor with a minimum inhibitory concentration of 10 μg/mL[1]. 1,3,5-Trihydroxy-4-prenylxanthone is a phosphodiesterase type 5 (PDE5) (Phosphodiesterase (PDE)) inhibitor with an IC50 value of 3.0 μM[3]. 1,3,5-Trihydroxy-4-prenylxanthone inhibits Lipopolysaccharide (LPS) (Lipopolysaccharides (HY-D1056))-induced NO production in RAW264.7 macrophages, and has anti-inflammatory activities[2].
Irsenontrine (E2027) maleate is an orally active and selective phosphodiesterase 9 (PDE9) inhibitor. Irsenontrine maleate can be used for the research of neurological diseases[1][2].
ITI-214 (free base) is a picomolar PDE1 inhibitor with excellent selectivity against other PDE family members and against a panel of enzymes, receptors, transporters, and ion channels, exhibits potent PDE1 inhibitory activity (Ki = 58 pM).IC50 value: 58 pM (Ki)Target: PDE1in vitro: ITI-214 exhibits picomolar inhibitory potency for PDE1, demonstrates excellent selectivity against all other PDE families. ITI214 exhibits excellent selectivity over other PDE familymembers. For instance, the Ki values of ITI214 against recombinant full-length human PDE1A, PDE1B, and PDE1C are 33 pM, 380 pM, and 35 pM, respectively. ITI214 is profiled in a panel of enzymes, receptors, transporters, and ion channels from Caliper at 10 μM, which is over 170000 times higher than its Ki for PDE1, and demonstrates good selectivity. [1]in vivo: ITI214 possesses a good overall profile with balanced physicochemical properties, excellent potency and selectivity, and good pharmacokinetics. ITI214 is found to significantly enhance memory performance in the test with a minimum effective dose of 3 mg/kg. [1]
Tadalafil is a PDE5 inhibitor with an IC50 value of 1.8 nM.IC50 Value: 1.8±0.4nM [1]Target: PDE 5Tadalafil is marketed in pill form for treating erectile dysfunction(ED) under the name Cialis, and under the name Adcirca for the treatment of pulmonary arterial hypertension. Tadalafil can elevate the level of cGMP in the corpus cavernosum and effectively improve ED of various causes and degrees.in vitro: Biochemical potencies (affinities) of these compounds for PDE5 determined by IC(50), K(D) (isotherm), K(D) (dissociation rate), and K(D) ((1/2) EC(50)), respectively, were the following: sildenafil (3.7 +/- 1.4, 4.8 +/- 0.80, 3.7 +/- 0.29, and 11.7 +/- 0.70 nM), tadalafil (1.8 +/- 0.40, 2.4 +/- 0.60, 1.9 +/- 0.37, and 2.7 +/- 0.25 nM); and vardenafil (0.091 +/- 0.031, 0.38 +/- 0.07, 0.27 +/- 0.01, and 0.42 +/- 0.10 nM). Thus, absolute potency values were similar for each inhibitor, and relative potencies were vardenafil >> tadalafil > sildenafil [1]. 0.5 ml tadalafil solutions with different concentrations were added (0.2, 0.1, 0.05 and 0.025 μg ml-1, respectively) into semen samples. In both groups, samples treated with 0.2 μg ml-1 tadalafil had significant increase in sperm motility after 2 h incubation [2].in vivo: The Tadalafil-treated group showed enhanced erectile function (intracavernosal pressure/mean arterial pressure) at 0.3, 0.5, 1, 3, and 5 Hz compared with diabetic group values at the respective frequencies (P <.05) that approached control values [3]. oral administration of tadalafil (20 mg) or sildenafil (100 mg) was given. In both groups, computer-assisted semen analysis parameters showed no significant difference. After the administration of tadalafil (2 h) and sildenafil (1 h), there was no significant difference observed in premature acrosome reaction incidence rate [2].Clinical trial: Study the Safety and Effectiveness of Tadalafil in Men With Problems Getting or Maintaining an Erection When Taken Prior to Desiring an Erection. Phase 3
TPN171 is a potent, selective and oral bioavailable inhibitor of phosphodiesterase type 5 (PDE5) with an IC50 of 0.62 nM, being developed for the treatment of pulmonary arterial hypertension (PAH)[1].
Mangostanol ((+)-Mangostanol)) is a natural polyoxygenated xanthone mangostanol isolated from the shell of Garcinia mangostana which has inhibitory effect on cAMP phosphodiesterase (PDE)[1].
IBMX is a broad-spectrum phosphodiesterase (PDE) inhibitor, with IC50s of 6.5, 26.3 and 31.7 μM for PDE3, PDE4 and PDE5, respectively.
Atizoram (CP-80,633), a cyclic nucleotide phosphodiesterase (PDE4) inhibitor, elevates plasma cyclic AMP levels and decreases tumor necrosis factor-α (TNFα) production in mice[1].
Crisaborole (AN-2728) is a potent inhibitor of PDE4 and cytokine release; inhibit PDE4 with an IC50 of 0.49 μM.
ATX inhibitor 18 is a potent ATX inhibitor with an IC50 value of 24.2 nM. ATX inhibitor 18 shows antiproliferative activity and anti-fibrosis activity. ATX inhibitor 18 suppresses collagen deposition in TGF-β-mediated cardiac fibrosis[1].
Piclamilast (RP 73401) is a phosphodiesterase 4 (PDE4) inhibitor, with IC50 values of 16 nM and 2 nM in pig aorta and eosinophil soluble, respectively[1][2][3][4].
AN3199 is a PDE4 inhibitor with IC50 of 94.5 nM.IC50 value: 94.5 nM [1]Target: PDE4The detailed information please refer to Compound 11 in the reference.
Carbazeran, a potent phosphodiesterase inhibitor, is aldehyde oxidase substrate. Carbazeran can be used for the research of metabolic disease[1].
PDE4-IN-10 (compound 7a) is a potent PDE4 inhibitor, with an IC50 of 7.01 μM for PDE4B. PDE4-IN-10 shows selectivity, microsomal stability, inhibition of TNF-α and no major toxicities in vitro[1].
VP3.15 dihydrobromide is a potent, orally bioavailable and CNS-penetrant dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, with IC50s of 1.59 μM and 0.88 μM for PDE7 and GSK-3, respectively. VP3.15 dihydrobromide has neuroprotective and neuroreparative activities, thus as potential combined anti-inflammatory and pro-remyelinating therapies for multiple sclerosis (MS)[1].
CDP-840 (GR259653X) is a potent, selective and orally active phosphodiesterase IV (PDE IV) inhibitor. CDP-840 inhibits antigen-induced early and late phase bronchoconstriction in conscious squirrel monkeys[1].
Autotaxin-IN-5 (compound 63), extracted from patent WO2018212534A1, is an Autotaxin inhibitor. Autotaxin-IN-5 has the potential to treat idiopathic pulmonary fibrosis[1].
Deltasonamide 1 TFA is a PDE6δ-KRas inhibitor. Deltasonamide 1 can inhibit PDE6δ-KRas with a KD of 203 pM. Deltasonamide 1 can be used for the research of tumors[1].
Rolipram is a selective phosphodiesterases PDE4 inhibitor with IC50s of 3 nM, 130 nM and 240 nM for PDE4A, PDE4B, and PDE4D, respectively.
R 80123 is the Z-isomer of R 79595, is also a highly selective phosphodiesterase inhibitor. The fuction is similar to R 80122 (HY-100615, Revizinone).In vivo: The administration of Revizinone improved the haemodynamic profile with an increase in cardiac output, a decrease in systemic vascular resistance and a stable heart rate and mean arterial blood pressure. [1] With regard to reconstitution of contractility and cardiac function Revizinone (E-isomer) is 10 fold more potent than R 79595 and nearly 100 fold more potent than R 80123 (Z-isomer). [2] Revizinone significantly increases global LV function and systolic wall thickening in ischemic areas at doses greater than or equal to 0.16 mg/kg i.v. [3]
Homo Sildenafil, an analog of Sildenafil, acts as a phosphodiesterase inhibitor[1].