pde4a

ML-030 是 PDE4抑制剂，对 PDE4A (IC50=6.7 nM)，PDE4A1 (IC50=12.9 nM)，PDE4B1 (IC50=48.2 nM)，PDE4B2 (IC50=37.2 nM)，PDE4C1 (IC50=452 nM) 和 PDE4D2 (IC50=49.2 nM)。

Enoximone 是一种选择性的，具有口服活性的磷酸二酯酶 III 抑制剂，也是正性肌力血管舒张剂。它通过抑制 cGMP 抑制的 PDE 来诱导血管舒张并增加细胞内 cAMP 水平。它还表现出 PDE4抑制作用，对心肌 PDE4A 的 IC50为 21.1 μM。它用于充血性心力衰竭的研究，并具有支气管扩张，抗哮喘和抗炎作用。

GSK356278 是一种有效的特异性磷酸二酯酶 4 (PDE4) 抑制剂，对人 PDE4A、PDE4B 和 PDE4D 的 pIC50 分别为 8.6、8.8 和 8.7。 GSK356278 具有抗炎、抗焦虑和增强认知的作用。

Rolipram (SB 95952) 是一种磷酸二酯酶 PDE4的选择性抑制剂，抑制 PDE4A，PDE4B 和 PDE4D 的 IC50分别为 3 nM，130 nM 和 240 nM。

PF-06445974 has good selectivity for PDE4D, excellent brain permeability, and has a high level of specific binding in the cold tracer study.

LASSBio-1632 is a novel anti-asthmatic lead candidate that selectively inhibits PDE4A and PDE4D isoenzymes, leading to the suppression of airway hyper-reactivity (AHR) and TNF-α production in lung tissue. With high experimental BBB permeability, LASSBio-1632 (7j) efficiently crosses the blood-brain barrier through passive diffusion [1].

LEO 39652 is a dual-soft PDE4 inhibitor with IC50s of 1.2 nM, 1.2 nM, 3.0 nM and 3.8 nM for PDE4A, PDE4B, PDE4C and PDE4D, respectively. LEO 39652 also inhibits TNF-α with an IC50 value of 6.0 nM. LEO 39652 is used for topical research of Atopic dermatitis (AD) [1]. LEO 39652 shows unbound in vitro potency when measured as LPS induced TNF-α release in human peripheral blood mononuclear cells (PBMC), incubated in serum free medium. LEO 39652 shows a relatively high binding to human serum albumin[2]. LEO 39652 is inactivated both in blood and liver (dual-soft) while stabled in the skin[1].Pharmacokinetic AnalysisLEO 39652 exhibits total clearance (rats 930, minipigs 200 and monkey 300 mL min kg) and ratio to total AUC (rats 4, minipigs 6 and monkey 6 %) following intravenous administration (rats 0.075, minipigs 0.5 and monkeys 2.0 mg kg)[1]. [1]. Jens Larsen, et al. Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3 H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5- a]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel Dual-Soft PDE4 Inhibitor for Topical Treatment of Atopic Dermatitis. J Med Chem. 2020 Dec 10;63(23):14502-14521.[2]. Stefan Eirefelt