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更新于：2025-01-23

PDE1C

更新于：2025-01-23

基本信息

别名

3',5'-cyclic-AMP phosphodiesterase、3',5'-cyclic-GMP phosphodiesterase、Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C

+ [7]

简介

Calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:8557689, PubMed:29860631). Has a high affinity for both cAMP and cGMP (PubMed:8557689). Modulates the amplitude and duration of the cAMP signal in sensory cilia in response to odorant stimulation, hence contributing to the generation of action potentials. Regulates smooth muscle cell proliferation. Regulates the stability of growth factor receptors, including PDGFRB (Probable).

关联

项与 PDE1C 相关的药物

BBB-022

靶点

PDE1C

作用机制

PDE1C抑制剂

在研机构-

原研机构

Eisai Co., Ltd.

在研适应症-

非在研适应症

脑卒中

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

AP-155

靶点

PDE1C

作用机制

PDE1C抑制剂 [+1]

在研机构-

原研机构

University of Genova

在研适应症-

非在研适应症

心肌缺血 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PDE1C 相关的临床结果

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100 项与 PDE1C 相关的转化医学

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0 项与 PDE1C 相关的专利（医药）

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162

项与 PDE1C 相关的文献（医药）

2024-11-05·ACS Omega

Development of a Candidate ¹¹C-Labeled Selective Phosphodiesterase 1 Radioligand for Positron Emission Tomography

Article

作者: Zhang, Yiding ; Patel, Jimmy S. ; Hu, Kuan ; Gao, Yabiao ; Zhou, Xin ; Li, Yinlong ; Kumata, Katsushi ; Chaudhary, Ahmad F. ; Xie, Lin ; Chen, Jiahui ; Zhang, Wei ; Fujinaga, Masayuki ; Yamasaki, Tomoteru ; Haider, Achi ; Yuan, Hongjie ; Zhang, Kuo ; Zhao, Chunyu ; Ran, Chongzhao ; Song, Zhendong ; Liang, Steven ; Zhang, Ming-Rong ; Collier, Thomas L. ; Mori, Wakana ; Rong, Jian

Phosphodiesterases (PDEs) constitute a superfamily of phosphohydrolytic enzymes that regulate intracellular second messenger signaling by hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate. Among the 11 subfamilies of PDEs, phosphodiesterase 1 (PDE1) stands out due to its broad implications in central and peripheral pathologies. There are three subtypes of PDE1: PDE1A, PDE1B, and PDE1C. While PDE1A and PDE1C are distributed in both the brain and peripheral organs, PDE1B is predominantly expressed in the brain, rendering it an attractive drug target for neurological and psychological disorders. Despite continuous efforts dedicated to the development of novel PDE1 inhibitors, a suitable PDE1 radioligand for human use is currently lacking. In this study, we present the identification and preclinical evaluation of [¹¹C]PF-04822163, a selective radioligand candidate for imaging PDE1 with positron emission tomography. PF-04822163 exhibits excellent potency toward PDE1 and demonstrates great target selectivity over other PDEs. Then, PF-04822163 was labeled with carbon-11 (half-life, 20 min) in favorable radiochemical yields (25 ± 10%, decay-corrected) and high molar activities (106-194 GBq/μmol). Further, in vitro and in vivo evaluations in rodents suggested that [¹¹C]PF-04822163 displayed good brain penetration and a rapid washout. Despite these promising performance characteristics of [¹¹C]PF-04822163, only marginal specific binding was observed in vivo. Further optimization of the scaffold is warranted to obtain favorable pharmacological and ADME properties.

2024-09-04·Antimicrobial Agents and Chemotherapy

Pharmacogenetic determinants of tenofovir diphosphate and lamivudine triphosphate concentrations in people with HIV/HBV coinfection

Article

作者: Tantawy, Marwa ; Bae, Jihyun ; Anderson, Peter L. ; Kwara, Awewura ; Gong, Yan ; Ganu, Vincent ; Yang, Hongmei ; Tachi, Kenneth ; Boamah, Isaac ; Bushman, Lane R. ; Ojewale, Oluwayemisi ; Lartey, Margaret ; Ellison, Lucas ; Obo-Akwa, Adjoa ; Langaee, Taimour

ABSTRACT The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by ABCC2 rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by SLC28A2 ) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations ( ABCC2 rs717620 and PDE1C rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3–547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified ABCC2 SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.

2024-06-01·Journal of Applied Physiology

Fetal sex and the relative reactivity of human umbilical vein and arteries are key determinants in potential beneficial effects of phosphodiesterase inhibitors

Article

作者: Tolsa, Jean-François ; Beaumann, Manon ; Peyter, Anne-Christine ; Baud, David ; Delhaes, Flavien ; Menétrey, Steeve ; Joye, Sébastien

The effects of phosphodiesterase inhibition on the umbilical circulation depend on the presence of intrauterine growth restriction, the fetal sex, vessel type, and vasoconstrictors implicated. The human umbilical vascular tone regulation is complex and depends on the amount and activity of specific proteins but also probably on the subcellular organization mediating protein interactions. Therefore, therapeutic interventions using phosphodiesterase inhibitors to improve the placental-fetal circulation should consider fetal sex and both umbilical vein and artery reactivity.

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