SA-ANP(SA-ANP) - 药物靶点：Aldosterone_在研适应症：难治性高血压，慢性肾病，射血分数保留型心力衰竭_专利_临床

概要

基本信息

药物类型

生物药

别名

mANP

靶点

Aldosterone

作用方式

拮抗剂

作用机制

醛固酮拮抗剂

治疗领域

心血管疾病泌尿生殖系统疾病

在研适应症

难治性高血压慢性肾病射血分数保留型心力衰竭

非在研适应症-

原研机构

Mayo Clinic

在研机构

Mayo Clinic

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

4

项与 SA-ANP 相关的临床试验

NCT06343298

/ Recruiting临床2期

A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE TITRATION, MULTI-CENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF SUBCUTANEOUS MANP WHEN ADMINISTERED ONCE DAILY FOR 42 DAYS IN PARTICIPANTS WITH DIFFICULT TO CONTROL HYPERTENSION/RESISTANT HYPERTENSION

This is a Phase 2 dose-titration study designed to evaluate the safety and efficacy of MANP subcutaneous injection compared to placebo in reducing baseline daytime systolic blood pressure (SBP), derived from 24-hour ambulatory blood pressure monitoring (ABPM), in subjects with hypertension who are taking 3 or more antihypertensive medications with different mechanisms of action.

开始日期2024-11-17

申办/合作机构

E-Star BioTech, LLC

[+3]

NCT05279742

/ Enrolling by invitation临床1/2期IIT

Enhancing the Natriuretic Peptide System in HFpEF: a Randomized Double-Blind Placebo-Controlled Triple Crossover Study

The purpose of this study is to look at the differences in how individuals with heart failure with preserved ejection fraction in the presence of chronic kidney disease (HFpEF-CKD) and exercise induced dyspnea without objective findings of fluid retention (HFpEF-EI) bodies function using drugs Sacubatril/Valsartan (Entresto) and MANP.

开始日期2022-11-04

申办/合作机构

Mayo Clinic

NCT05247528

/ Completed临床1期

A Phase 1B, Multiple Ascending Dose Trial Examining The Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects

A randomized, double-blind, placebo-controlled multiple ascending dose study in hypertensive subjects on stable doses of at least three hypertensive drugs for at least 6 weeks prior to Screening. The study will consist of screening, PK-unit admittance, and safety follow up periods.
Subjects will be randomized at a 6:2 ratio of either MANP or placebo and will be stratified by race in each dosage cohort. The entire first Cohort will be given the lowest dosage with subsequent cohorts progressing sequentially to the higher doses depending on safety and tolerability of the previous cohort.
Endpoints not related to the safety reviews will be analyzed after the last patient last visit (LPLV).

开始日期2021-12-20

申办/合作机构

E-Star BioTech, LLC

[+2]

100 项与 SA-ANP 相关的临床结果

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100 项与 SA-ANP 相关的转化医学

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100 项与 SA-ANP 相关的专利（医药）

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13

项与 SA-ANP 相关的文献（医药）

2023-01-01·Frontiers in chemistry

Green synthesis of MgO nanoparticles and its antibacterial properties.

Article

作者: Ashgar, Sami S. ; Manjunath, Ramya ; Babalghith, Ahmad O. ; Rotti, Rajeshwari B. ; Abdulaziz, Osama ; Mayegowda, Shilpa Borehalli ; Gnanaprakash, A. P. ; Alghamdi, Saad ; Sunitha, D. V. ; El-Lateef, Amal Ezzat Abd ; Allahyani, Mamdouh ; Alsaiari, Ahad Amer ; Roy, Arpita ; Almehmadi, Mazen ; Khidir, Elshiekh B. ; Aljuaid, Abdulelah

Magnesium oxide nanostructured particles (NP) were prepared using a simple solution combustion technique using different leaf extracts such as Mangifera indica (Mango - Ma), Azadirachta indica (Neem-Ne), and Carica papaya (Papaya-Pa) as surfactants. The highly crystalline phase of MgO nanostructures was confirmed by PXRD and FTIR studies for 2 h 500°C calcined samples. To analyze the characteristics of obtained material-MaNP, NeNP, and PaNP for dosimetry applications, thermoluminescence (TL) studies were carried out for Co-60 gamma rays irradiated samples in the dose range 10-50 KGy; PaNP and NeNP exhibited well-defined glow curve when compared with MaNP samples. In addition, it was observed that the TL intensity decreases, with increase in gamma dose and the glow peak temperature is shifted towards the higher temperature with the increase in heating rate. The glow peak was segregated using glow curve deconvolution and thermal cleaning method. Kinetic parameters estimated using Chen's method, trap depth (E), and frequency factor (s) were found to be 0.699, 7.408, 0.4929, and 38.71, 11.008, and 10.71 for PaNP, NeNP, and MaNP respectively. The well-resolved glow curve, good linear behavior in the dose range of 10-50, KGy, and less fading were observed in PaNP as compared with MaNP and NeNP. Further, the antibacterial activity was checked against human pathogens such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A visible zone of clearance was observed at 200 and 100 μg/mL by the PaNP and NeNP, indicating the death of colonies by the nanoparticles. Therefore, PaNP nanomaterial is a potential phosphor material for dosimetry and antibacterial application compared to NeNP and MaNP.

2022-08-01·Hypertension

MANP Activation Of The cGMP Inhibits Aldosterone Via PDE2 And CYP11B2 In H295R Cells And In Mice

Article

作者: Pellegrini, Manuela ; Burnett, John C. ; Naro, Fabio ; Nikolaev, Viacheslav O. ; Chen, Yang ; Cardarelli, Silvia ; Lee, Hon-Chi ; Ma, Xiao ; Iyer, Seethalakshmi R.

Background:Aldosterone is a critical pathological driver for cardiac and renal diseases. We recently discovered that mutant atrial natriuretic peptide (MANP), a novel atrial natriuretic peptide (ANP) analog, possessed more potent aldosterone inhibitory action than ANP in vivo. MANP and natriuretic peptide (NP)-augmenting therapy sacubitril/valsartan are under investigations for human hypertension treatment. Understanding the elusive mechanism of aldosterone inhibition by NPs remains to be a priority. Conflicting results were reported on the roles of the pGC-A (particulate guanylyl cyclase A receptor) and NP clearance receptor in aldosterone inhibition. Furthermore, the function of PKG (protein kinase G) and PDEs (phosphodiesterases) on aldosterone regulation are not clear.Methods:In the present study, we investigated the molecular mechanism of aldosterone regulation in a human adrenocortical cell line H295R and in mice.Results:We first provided evidence to show that pGC-A, not NP clearance receptor, mediates aldosterone inhibition. Next, we confirmed that MANP inhibits aldosterone via PDE2 (phosphodiesterase 2) not PKG, with specific agonists, antagonists, siRNA silencing, and fluorescence resonance energy transfer experiments. Further, the inhibitory effect is mediated by a reduction of intracellular Ca2+ levels. We then illustrated that MANP directly reduces aldosterone synthase CYP11B2 (cytochrome p450 family 11 subfamily b member 2) expression via PDE2. Last, in PDE2 knockout mice, consistent with in vitro findings, embryonic adrenal CYP11B2 is markedly increased.Conclusions:Our results innovatively explore and expand the NP/pGC-A/3',5', cyclic guanosine monophosphate (cGMP)/PDE2 pathway for aldosterone inhibition by MANP in vitro and in vivo. In addition, our data also support the development of MANP as a novel ANP analog drug for aldosterone excess treatment.

2022-04-01·Hypertension1区 · 医学

MANP (M-Atrial Natriuretic Peptide) Reduces Blood Pressure and Furosemide-Induced Increase in Aldosterone in Hypertension

1区 · 医学

Article

作者: Dzhoyashvili, Nina A. ; Burnett, John C. ; Chen, Horng H. ; Iyer, Seethalakshmi R.

Background:cGMP MANP (M-atrial natriuretic peptide) is a best-in-class activator of the pGC-A (particulate guanylyl cyclase A) receptor. Furosemide increases the effectiveness of antihypertensive agents, but activates renin-angiotensin-aldosterone system. We aimed to investigate for the first time cardiorenal and neurohumoral actions of MANP in a genetic model of hypertension in spontaneously hypertensive rats. We also assessed how MANP would potentiate the blood pressure (BP)–lowering actions of furosemide while reducing the production of aldosterone.Methods:Spontaneously hypertensive rats (N=60) were randomized in vehicle, MANP, furosemide, or MANP+furosemide groups. Furosemide (1, 5, 10 mg/kg) was given as a single bolus which in MANP+furosemide groups was followed by a 60-minute infusion of MANP.Results: BP was reduced in MANP300 (300 pmol/[kg·min]) and MANP600 (600 pmol/[kg·min]) groups ( P <0.05) and was accompanied by significant increase in plasma cyclic guanosine monophosphate. Furosemide alone reduced BP but less compared with MANP with no change in plasma cyclic guanosine monophosphate. MANP+furosemide resulted in the greatest BP reduction and significant increase in plasma cyclic guanosine monophosphate in Fs5+MANP300, Fs10+MANP300, and Fs10+MANP600. Plasma aldosterone increased in furosemide groups, which was significantly attenuated in MANP+furosemide groups. Natriuresis and diuresis increased in all treated groups ( P <0.05) with no significant differences between furosemide and furosemide+MANP. In vitro, MANP increased cyclic guanosine monophosphate level in human vascular cells. Conclusions:We provide novel evidence that MANP potentiates the BP-lowering actions of furosemide, suppresses the activation of renin-angiotensin-aldosterone system, and preserves renal function. These data are highly relevant to clinical needs in the treatment of hypertension and heart failure.

100 项与 SA-ANP 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
难治性高血压	临床2期	美国	Mayo Clinic	2024-11-17
慢性肾病	临床2期	美国	Mayo Clinic	2022-11-04
射血分数保留型心力衰竭	临床2期	美国	Mayo Clinic	2022-11-04

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ESC2024	临床1期	难治性高血压	36	MANP	膚鹹餘網淵糧齋餘選選(壓蓋網網製繭築艱獵壓) = There were no reported drug related serious adverse events 範簾壓遞遞壓壓範壓夢 (觸壓網獵顧簾簾鬱襯淵 ) 更多	积极	2024-08-30
				Placebo
NCT03781739 (ESC2023)	临床1期	代谢综合征 \| 高血压	22	MANP	願餘襯蓋窪網獵糧夢遞(衊鑰遞蓋觸糧窪網構鹽) = 夢鏇觸餘膚膚糧糧壓醖鏇蓋觸醖鏇窪鑰鬱簾艱 (餘鬱範廠鏇網範廠構憲 ) 更多	-	2023-08-26
ESC2016	临床1期	高血压	-	ZD100	鏇願糧構窪膚製顧獵遞(構蓋製膚鬱壓鬱鹹鏇鏇) = 憲壓憲鑰鹽簾觸範餘獵獵積築願襯淵積鹹築選 (獵窪遞選鏇餘積網衊鹹 ) 更多	-	2016-08-28
				Placebo	廠齋鑰鹹壓遞膚簾憲網(築壓網鬱夢鬱鏇糧遞顧) = 網選選獵膚憲顧繭夢糧鑰構願艱製蓋遞鹹廠醖 (構製膚淵廠鹽襯餘餘窪 ) 更多