PPI-1019(PPI-1019) - 药物靶点：APP_专利_临床

概要

基本信息

药物类型

合成多肽

别名

Apan

靶点

APP

作用方式

抑制剂

作用机制

APP抑制剂(β-淀粉状蛋白A4抑制剂)

治疗领域

神经系统疾病

在研适应症-

非在研适应症

阿尔茨海默症

原研机构

GSK Plc

在研机构-

非在研机构

Praecis Pharmaceuticals, Inc.

权益机构-

最高研发阶段无进展临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C36H54N6O5

InChIKeyTUSUWHFYKZZRIG-JQWMYKLHSA-N

CAS号290828-45-4

Sequence Code 13764991

关联

2

项与 PPI-1019 相关的临床试验

NCT00100334

/ Completed临床1/2期

Multiple Dose Safety and Preliminary Pharmacodynamic Study of PPI-1019 in Subjects With Mild-Moderate Alzheimer's Disease

This is a single-center, double-blind, inpatient study followed by an outpatient, placebo-controlled, multiple-IV injection evaluation of the safety and tolerability of PPI-1019 in subjects with mild-moderate Alzheimer's disease (AD). The primary objective of the study is to assess the safety of multiple IV injections of PPI-1019 in subjects with mild-moderate Alzheimer's disease.

开始日期2004-12-01

申办/合作机构

Praecis Pharmaceuticals, Inc.

NCT00100282

/ Completed临床1期

Single Dose Escalation Safety Study of PPI-1019 in Patients With Mild-Moderate Alzheimer's Disease

This is a multi-center, double-blind, inpatient study followed by outpatient, placebo-controlled, single-dose, dose-escalation evaluation of the safety and tolerability of PPI-1019 in patients with mild-moderate Alzheimer's disease (AD). Up to 12 sequential cohorts of 8 patients (6 active and 2 placebo) will be given a single PPI-1019 dose intravenously (IV) over 1 minute in order to determine a maximum tolerated dose (MTD). The MTD will be the dose immediately below the not-tolerated dose.

开始日期2003-05-01

申办/合作机构

Praecis Pharmaceuticals, Inc.

100 项与 PPI-1019 相关的临床结果

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100 项与 PPI-1019 相关的转化医学

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100 项与 PPI-1019 相关的专利（医药）

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13

项与 PPI-1019 相关的文献（医药）

2024-11-01·Echocardiography

Presence of Apical Aneurysm and Its Impact on Left Ventricular Mechanics and Mechano‐Energetic Coupling in Patients With Apical Hypertrophic Cardiomyopathy

Article

作者: Horvath, Sofia A. ; Guigui, Sarah A. ; Elajami, Tarec K. ; Fernandez, Rafle ; Mihos, Christos G. ; Venkataraman, Pranav

ABSTRACTBackgroundLeft ventricular (LV) apical aneurysms (ApAn+) occur in 10%–15% of apical hypertrophic cardiomyopathy (ApHCM) patients and confer considerable morbidity. We hypothesized that ApAn+ adversely impact ventricular mechanics and mechano‐energetic coupling in ApHCM.MethodsNinety‐eight ApHCM patients were identified, of which nine (9%) had ApAn+ and were compared with 89 (91%) who did not (ApAn−). 2D speckle‐tracking echocardiography assessed ventricular mechanics using LV global longitudinal strain (GLS) and torsion, and mechano‐energetic coupling as myocardial work indices. Clinical events over follow‐up were adjudicated.ResultsMean age was 64 ± 15 years, 46% were female, and 3% had an HCM family history, with similar clinical risk factors between groups. Of the nine ApAn+ patients, there were six small (<2 cm) and three moderate‐sized (2‐4 cm) aneurysms. There was no difference in LV ejection fraction (65 ± 15 vs. 67 ± 11%, p = 0.51) or GLS (−9.6 ± 3.3 vs. −11.9 ± 3.9%, p = 0.09) between ApAn+ versus ApAn−. ApAn+ patients had greater myocardial global wasted work (347 ± 112 vs. 221 ± 165 mmHg%, p = 0.03) and lower global work efficiency (GWE, 75 ± 5 vs. 82 ± 8%, p = 0.006). LV GLS (β = −0.67, p < 0.001), ApAn+ (β = −0.15, p = 0.04), and twist rate (β = −0.14, p = 0.04) were independently associated with GWE. At 3.9‐year follow‐up, cardiovascular mortality (4%) and heart failure hospitalization (14%) events were similar between groups.ConclusionApHCM patients with ApAn+ are characterized by more impaired LV mechano‐energetic coupling when compared with ApAn−. ApAn+ is independently associated with worse GWE.

2023-04-01·Apoptosis

Design and cytotoxic evaluation via apoptotic and antiproliferative activity for novel 11(4-aminophenylamino)neocryptolepine on hepatocellular and colorectal cancer cells

Article

作者: Abd Eldaim, Mabrouk Attia ; Elmongy, Elshaymaa I ; Elmadbouh, Ibrahim ; El Sayed, Ibrahim El Tantawy ; El-Gendy, Saad M ; Nagy, Esraa Tariq ; Ahmed, Abdullah A S ; El-Gokha, Ahmed A

The current study evaluated the cytotoxic activity of 11(4-Aminophenylamino)neocryptolepine (APAN), a novel derivative of neocryptolepine, on hepatocellular (HepG2) and colon (HCT-116) carcinoma cell lines as well as, the possible molecular mechanism through which it exerts its cytotoxic activity. The APAN was synthesized and characterized based on their spectral analyses. Scanning for anticancer target of APAN by Swiss software indicated that APAN had highest affinity for protein tyrosine kinase 6 enzyme. Furthermore, Super pred software indicated that APAN can be indicated in hepatic and colorectal cells with 92%. Molecular docking studies indicated that the binding affinity scores of APAN for protein PDB code: 6CZ4 of tyrosine kinase 6 recorded of - 6.6084 and RMSD value of 0.8891°A, while that for protein PDB: 7JL7 of caspase 3 was - 6.1712 and RMSD of 0.8490°A. Treatment of HepG2 and HCT-116 cells with APAN induced cytotoxicity with IC₅₀ of 2.6 and 1.82 μg/mL respectively. In addition, it induced injury and serious morphological changes in cells including, disappearance of microvilli, membrane blebbing, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin. Moreover, APAN significantly increased protein expression of annexin V (apoptotic marker). Furthermore, APAN significantly increased protein expression of caspase 3 and P53. However, it significantly reduced secretion of VEGF protein into the medium and decreased protein expression of PCNA and Ki67 in HepG2 and HCT-116 cells. This study indicated that APAN had cytotoxic activity against HepG2 and HCT-116 cells via increasing the expression of apoptotic proteins and reducing the expression of proliferative proteins.

2020-08-12·Journal of Agricultural and Food Chemistry1区 · 农林科学

APAn, a Class of ABA Receptor Agonism/Antagonism Switching Probes

1区 · 农林科学

Article

作者: Che, Chuanliang ; Qin, Zhaohai ; Lu, Huizhe ; Xu, Yanjun ; Zeng, Yuejuan ; Xu, Yefei ; Zhang, Xueqin ; Li, Jia-Qi ; Xiao, Yumei

In plants, biosynthesized ABA undergoes two important physiological processes of signal transduction and metabolism simultaneously. In this study, we described a class of ABA receptor agonist/antagonist switching probes APAn, which can regulate the agonistic activity or antagonistic activity according to the length of a 6'-alkoxyl chain. From APA1 to APA6, with the extension of the alkoxyl chain, it showed a gradually increased receptor-binding potential and decreased HAB1 inhibition activity. Theoretical analysis based on molecular docking and molecular dynamics simulation revealed that some factors outside the ligand-binding pocket in receptors could also affect the binding of the ligand to the receptor, for example, the van der Waals interaction between the alkyl chain in APAn and the 3'-tunnel of ABA receptors made it bind more tightly than iso-PhABA. This enhanced binding made it an antagonist rather than a weakened agonist.

100 项与 PPI-1019 相关的药物交易

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