A Randomized, Double-Blind, Placebo Controlled, Multicenter 2a Study to Assess Safety, Daily Respiratory Symptoms, PK, and Biomarker Variations After Administration of Either YPL-001, or Placebo in Patients With Moderate-to-Severe COPD.

This is a Phase 2a, proof-of-concept, multicenter, randomized, double-blind, double dummy, 3-treatment, parallel study, with low and high YPL 001 doses (low dose and high dose twice daily [BID]) and a placebo control in moderate to severe Chronic Obstructive Pulmonary Disease (COPD) patients.

Start Date04 Jun 2015

Sponsor / Collaborator

Yungjin Pharm. Co., Ltd.

100 Clinical Results associated with YPL-001

100 Translational Medicine associated with YPL-001

100 Patents (Medical) associated with YPL-001

Literatures (Medical) associated with YPL-001

13 Apr 2023·International journal of molecular sciences

Verproside, the Most Active Ingredient in YPL-001 Isolated from Pseudolysimachion rotundum var. subintegrum, Decreases Inflammatory Response by Inhibiting PKCδ Activation in Human Lung Epithelial Cells.

Article

Author: Oh, Eun Sol ; Kim, Doo-Young ; Kim, Mun-Ock ; Lee, Su Ui ; Oh, Sei-Ryang ; Song, Yu Na ; Kim, Tae-Don ; Lee, Jae-Won ; Ryu, Hyung Won ; Lee, Jinhyuk ; Park, Ji-Yoon ; Ro, Hyunju ; Hong, Sung-Tae

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems.YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD.Although YPL-001 has completed clin. trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear.To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells.Here, we show that verproside among the six iridoids most strongly suppresses inflammation.Both TNF/NF-κB-induced MUC5AC expression and PMA/PKCδ/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside.Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells.The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCδ.Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCδ activation and mucus overproductionAltogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCδ activation and its downstream pathways.

01 Feb 2018·PhytomedicineQ2 · MEDICINE

Piscroside C inhibits TNF-α/NF-κB pathway by the suppression of PKCδ activity for TNF-RSC formation in human airway epithelial cells

Q2 · MEDICINE

Article

Author: Lee, Jinhyuk ; Kim, Mun-Ock ; Yuk, Heung Joo ; Lee, Su Ui ; Oh, Sei-Ryang ; Hong, Sung-Tae ; Choi, Ji-Hee ; Ro, Hyunju ; Ryu, Hyung Won ; Lee, Seoghyun

BACKGROUNDPiscroside C, isolated from Pseudolysimachion rotundum var. subintegrum, is a novel iridoid glycoside with therapeutic efficacy in a mouse model of chronic obstructive pulmonary disease (COPD). Piscroside C has been reported as a constituent of YPL-001 (under Phase 2a study, ClinicalTrials.gov identifier NCT02272634).PURPOSETo investigate the mechanisms behind piscroside C therapeutic effects on COPD in human airway epithelial NCI-H292 cells.METHODSWe tested if piscroside C effectively suppresses MUC5AC gene expression and TNF-RSC/IKK/NF-κB cascades in TNF-α-stimulated NCI-H292 cells by employing, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, luciferase reporter assays, chromatin immunoprecipitation assays and immunoprecipitation.RESULTSPiscroside C markedly suppressed the expression of TNF-α-induced MUC5AC mucus protein by inhibiting the transcriptional activity of NF-κB in NCI-H292 cells. Indeed, piscroside C negatively regulated the function of TNF receptor 1 signaling complex (TNF-RSC, an upstream regulator of the NF-κB pathway) without affecting its extracellular interaction with the TNF-α ligand. This inhibitory effect by piscroside C is mediated by the inactivation of protein kinase C (PKC), an essential regulator of TNF-RSC. PKC inactivation by piscroside C results in decreased PKCδ binding to a TRAF2 subunit of TNF-RSC and subsequent reduced IKK phosphorylation, resulting in NF-κB inactivation.CONCLUSIONWe propose that piscroside C is a promising therapeutic constituent of YPL-001 through its inhibition of PKCδ activity in the TNF-RSC/IKK/NF-κB/MUC5AC signaling cascade.

MoleculesQ3 · CHEMISTRY

Picroside II Isolated from Pseudolysimachion rotundum var. subintegrum Inhibits Glucocorticoid Refractory Serum Amyloid A (SAA) Expression and SAA-induced IL-33 Secretion

Q3 · CHEMISTRY

ArticleOA

Author: Lee, Kiram ; Oh, Sei-Ryang ; Ryu, Hyung Won ; Lee, Hyun-Jun ; Gu, Young-Mi ; Choi, Jin ; Choi, Bo Kyong

Chronic obstructive pulmonary disease (COPD) is a major inflammatory lung disease characterized by irreversible and progressive airflow obstruction. Although corticosteroids are often used to reduce inflammation, steroid therapies are insufficient in patients with refractory COPD. Both serum amyloid A (SAA) and IL-33 have been implicated in the pathology of steroid-resistant lung inflammation. Picroside II isolated from Pseudolysimachion rotundum var. subintegrum (Plantaginaceae) is a major bioactive component of YPL-001, which has completed phase-2a clinical trials in chronic obstructive pulmonary disease patients. In this study, we investigated whether picroside II is effective in treating steroid refractory lung inflammation via the inhibition of the SAA-IL-33 axis. Picroside II inhibited LPS-induced SAA1 expression in human monocytes, which are resistant to steroids. SAA induced the secretion of IL-33 without involving cell necrosis. Picroside II, but not dexamethasone effectively inhibited SAA-induced IL-33 expression and secretion. The inhibitory effect by picroside II was mediated by suppressing the mitogen-activated protein kinase (MAPK) p38, ERK1/2, and nuclear factor-κB pathways. Our results suggest that picroside II negatively modulates the SAA-IL-33 axis that has been implicated in steroid-resistant lung inflammation. These findings provide valuable information for the development of picroside II as an alternative therapeutic agent against steroid refractory lung inflammation in COPD.

100 Deals associated with YPL-001

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Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Disease, Chronic Obstructive	Phase 2	US	Yungjin Pharm. Co., Ltd.	04 Jun 2015

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02272634 (CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	61	YPL-001 80 mg (Treatment A)	gdjtvioabw(bdvndrvevb) = qnpbizmrdd pxzykfhzns (abygzgdnck, cmlxbsvjny - txuafghmkm) View more	-	25 Jun 2021
				YPL-001 160 mg (Treatment B)	gdjtvioabw(bdvndrvevb) = yqogmhifjh pxzykfhzns (abygzgdnck, fduvdxqifs - wcxumhtvsq) View more

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