Delving into the Latest Updates on Simmerafil with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

TPN171

Target

PDE5A

Action

inhibitors

Mechanism

PDE5A inhibitors(Phosphodiesterase 5A inhibitors)

Therapeutic Areas

Urogenital Diseases

Active Indication

Erectile Dysfunction

Inactive Indication

Idiopathic pulmonary arterial hypertensionPulmonary Arterial HypertensionRenal Insufficiency

Originator Organization

Topharman Shanghai Co. Ltd.

Active Organization

Suzhou Thery Pharmaceutical Co., Ltd.

Shanghai Institute of Materia Medica Chinese Academy of Sci

Suzhou Vigonvita Life Sciences Co.,Ltd

Inactive Organization

Shandong Tefaman Pharmaceutical Co Ltd.

Topharman Shanghai Co. Ltd.

License Organization-

Drug Highest PhaseNDA/BLA

First Approval Date-

RegulationSpecial Review Project (China)

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主要目的：在中国健康男性受试者中评估单次口服TPN171H片对精液质量（精子活动力、活动率、数量、密度、形态、精液粘稠度、体积）的急性影响；考察TPN171H在精浆中的暴露量。次要目的：观察健康男性受试者单次口服TPN171H片的安全性。

[Translation]

Primary objective: To evaluate the acute effects of a single oral administration of TPN171H tablets on semen quality (sperm motility, motility, number, density, morphology, semen viscosity, and volume) in healthy Chinese male subjects; to investigate the exposure of TPN171H in seminal plasma. Secondary objective: To observe the safety of a single oral administration of TPN171H tablets in healthy male subjects.

Start Date15 Nov 2022

Sponsor / Collaborator

Suzhou Vigonvita Life Sciences Co.,Ltd

[+1]

NCT05585931

/ CompletedPhase 1

Evaluate the Acute Effects of a Single Oral Dose of TPN171H on Semen Function in Healthy Male Subjects in China

This study is a phaseⅠstudy to determine the acute effects of TPN171H on semen function in healthy male subjects.

Start Date15 Nov 2022

Sponsor / Collaborator

Suzhou Vigonvita Life Sciences Co.,Ltd

100 Clinical Results associated with Simmerafil

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100 Translational Medicine associated with Simmerafil

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100 Patents (Medical) associated with Simmerafil

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11

Literatures (Medical) associated with Simmerafil

01 Feb 2025·Clinical and Translational Science

Hemodynamic and Pharmacokinetic Interactions of TPN171 with Alcohol in Healthy Male Subjects

Article

Author: Xu, Wenjing ; Yu, Chen ; Jia, Jingying ; Duan, Huaqing ; Wang, Zhen ; Qian, Hongjie ; Liu, Ye ; Chen, Qian ; Wang, Hang ; Wang, Yu ; Liang, Liyu ; Cheng, Jie

ABSTRACTThis study aimed to evaluate the effects of the concomitant administration of TPN171 and alcohol on hemodynamic and pharmacokinetic characteristics in healthy Chinese male subjects. Fifteen eligible subjects were randomly assigned to one of three sequences, each comprising three treatments: Treatment A (placebo +0.5 g/kg alcohol), Treatment B (TPN171 + 0.5 g/kg alcohol), and Treatment C (TPN171 + placebo). Enrolled subjects were administered with 10 mg TPN171 and/or 0.5 g/kg alcohol in fasting state in a randomized crossover design. Blood pressure, pulse rate (PR), blood samples, and breath alcohol test were measured at designated time points for hemodynamic and pharmacokinetic analyses. Compared with 10 mg TPN171 alone, administration of 10 mg TPN171 + 0.5 g/kg alcohol significantly lowered the area under the effect–time curve from 0 to 4 h (AUEC0‐4h) of systolic blood pressure (95% confidence interval [CI]: −29.75 to −0.83, p = 0.039) and significantly increased AUEC0–4h of PR (95% CI: 7.47–28.92, p = 0.003). Compared with 0.5 g/kg alcohol alone, administration of 10 mg TPN171 + 0.5 g/kg alcohol contributed to significantly higher maximal increase of PR (95% CI: 2.78–9.44, p = 0.002) and AUEC0‐4h of PR (95% CI: 1.08–24.52, p = 0.035). Alcohol had no influence on the pharmacokinetics of TPN171, and vice versa. Though the concomitant administration of TPN171 and alcohol induced a more pronounced increase in PR, this did not result in clinical symptoms or heart rate increase‐related adverse events, indicating that the combined use was generally safe and well‐tolerated.

01 Jan 2023·Acta Pharmacologica Sinica

Pharmacokinetics, mass balance, and metabolism of [14C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension

Article

Author: Yu, Chen ; Cheng, Huan ; Diao, Xing-Xing ; Yu, Jing-Hua ; Liu, Gang-Yi ; Wang, Zhen ; Yang, Fei-Pu ; Yao, Xiu-Mei ; Duan, Hua-Qing ; Liu, Yan-Mei ; Liu, Yin ; Yu, Cheng-Yin ; Odilov, Abdullajon ; He, Yi-Fei ; Shen, Jing-Shan ; Tian, Guang-Hui

TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED), which currently is undergoing phase II clinical trials in China. In this single-center, single-dose, nonrandomized, and open design study, radiolabeled [¹⁴C]TPN171 was used to investigate the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of TPN171 in 6 healthy Chinese male volunteers. Each volunteer was administered a single oral suspension of 10 mg (100 μCi) of [¹⁴C]TPN171. We found that TPN171 was absorbed rapidly in humans with a peak time (T_max) of 0.667 h and a half-life (t_1/2) of approximately 9.89 h in plasma. Excretion of radiopharmaceutical-related components was collected 216 h after administration, accounting for 95.21% of the dose (46.61% in urine and 48.60% in feces). TPN171 underwent extensive metabolism in humans. Twenty-two metabolites were detected in human plasma, urine, and feces using a radioactive detector combined with a high-resolution mass spectrometer. According to radiochromatograms, a glucuronide metabolite of O-dealkylated TPN171 exceeded 10% of the total drug-related components in human plasma. However, according to the Food and Drug Administration (FDA) guidelines, no further tests are needed to evaluate the safety of this metabolite because it is a phase II metabolite, but the compound is still worthy of attention. The main metabolic biotransformation of TPN171 was mono-oxidation (hydroxylation and N-oxidation), dehydrogenation, N-dealkylation, O-dealkylation, amide hydrolysis, glucuronidation, and acetylation. Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites, and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent. According to the incubation data, M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9), followed by UGT1A7 and UGT1A10.

01 Aug 2022·Vascular Pharmacology

TPN171H alleviates pulmonary hypertension via inhibiting inflammation in hypoxia and monocrotaline-induced rats

Article

Author: Wang, Zhen ; Li, Qianbin ; Wu, Chunhui ; Yin, Minghui ; Tettey, Abraham Terkpertey ; Li, Lijun ; Tang, Siyuan ; Li, Xiaohui ; He, Xiangrong ; Zhao, Congke ; Hu, Liqing ; Wang, Yu ; Shen, Jingshan

Pulmonary hypertension (PH) is a progressive and life-threatening disease with poor prognosis despite many advances in medical therapy over the past 20 years. Novel therapies which target on the underlying pathology of PH are still urgent to be met. TPN171H is a recently found new compound that exhibits potent pharmacological effects in PH via inhibiting phosphodiesterase type 5 (PDE-5). However, as one icariin derivative, the anti-inflammatory effects of TPN171H for treating PH are not clear. The present study was designed to investigate the therapeutical effect of TPN171H against inflammation in PH and reveal the underlying mechanism. Hypoxia and monocrotaline (MCT)-induced PH rat models were established, which were treated by oral administration of TPN171H (5, 25 mg/kg/d) or sildenafil (25 mg/kg/d). The right ventricle systolic pressure (RVSP), right ventricle hypertrophy index (RVHI) and vascular remodeling were measured. The results suggested that TPN171H significantly reduced RVSP and RVHI, and reversed pulmonary vascular remodeling in rats with both models. Furthermore, in in vivo and in vitro research, our data suggested that TPN171H remarkably suppressed cathepsin B-mediated NLRP3 inflammasome activation, which may contribute to its therapeutical function for PH.

100 Deals associated with Simmerafil

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Erectile Dysfunction	NDA/BLA	China	Suzhou Thery Pharmaceutical Co., Ltd.	23 Sep 2023
Erectile Dysfunction	NDA/BLA	China	Suzhou Vigonvita Life Sciences Co.,Ltd	23 Sep 2023
Idiopathic pulmonary arterial hypertension	Phase 2	China	Suzhou Vigonvita Life Sciences Co.,Ltd	16 Nov 2020
Idiopathic pulmonary arterial hypertension	Phase 2	China	Shanghai Institute of Materia Medica Chinese Academy of Sci	16 Nov 2020
Idiopathic pulmonary arterial hypertension	Phase 2	China	Topharman Shanghai Co. Ltd.	16 Nov 2020
Idiopathic pulmonary arterial hypertension	Phase 2	China	Shandong Tefaman Pharmaceutical Co Ltd.	16 Nov 2020
Pulmonary Arterial Hypertension	Phase 2	China	Suzhou Vigonvita Life Sciences Co.,Ltd	16 Nov 2020
Pulmonary Arterial Hypertension	Phase 2	China	Shanghai Institute of Materia Medica Chinese Academy of Sci	16 Nov 2020
Pulmonary Arterial Hypertension	Phase 2	China	Shandong Tefaman Pharmaceutical Co Ltd.	16 Nov 2020
Pulmonary Arterial Hypertension	Phase 2	China	Topharman Shanghai Co. Ltd.	16 Nov 2020