Delving into the Latest Updates on Uridine triphosphate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Prolucin, UTP

+ [3]

Target

P2Y2 receptor

Mechanism

P2Y2 receptor agonists(Purinergic receptor P2Y2 agonists)

Therapeutic Areas

NeoplasmsInfectious DiseasesRespiratory Diseases+ [4]

Active Indication-

Inactive Indication

BronchitisCiliary Motility DisordersCystic Fibrosis+ [3]

Originator Organization

Merck Serono SA

Active Organization-

Inactive Organization

Merck Serono SA

Inspire Pharmaceuticals, Inc.

Merck Sharp & Dohme Corp.

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC9H15N2O15P3

InChIKeyPGAVKCOVUIYSFO-XVFCMESISA-N

CAS Registry63-39-8

Previous research has identified adenosine triphosphate (ATP) as an important vasodilator that is released from red blood cells during exercise and exposure to hypoxic environments in adult humans. Further, older adults appear to have lower blood flow during both of these stressors and also have lower amounts of ATP released from their red blood cells. However, the contribution of ATP to vasodilation in response to exercise and hypoxia is currently unknown due to the lack of an effective ATP receptor antagonist. We aim to determine whether Vitamin B6 or its metabolite, Pyridoxal-5-Phosphate (PLP) is an effective ATP receptor antagonist.

Start Date07 Feb 2019

Sponsor / Collaborator

Colorado State University

NCT01381666 / TerminatedPhase 2

Evaluation of the Diagnostic Utility of INS316 in Patients With Interstitial Lung Diseases (01-701)

The objective of the present work is to explore and compare the diagnostic quality of sputum specimens obtained by BAL, induction with hypertonic saline (3%), and induction with INS316 in patients diagnosed with interstitial lung diseases.

Start Date01 Jan 2003

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT00008255 / CompletedPhase 2IIT

Evaluation Of Uridine 5-Triphosphate Solution For Inhalation (UTP) As An Adjunct In The Diagnosis Of Lung Cancer By Sputum Cytology

RATIONALE: Doctors can diagnose lung cancer by collecting mucus coughed up from the lungs and examining it under a microscope to look for cancer cells. Breathing in INS316 may make it easier for patients to cough up mucus.
PURPOSE: Randomized phase II trial to study the effectiveness of INS316 in helping to diagnose lung cancer.

Start Date01 Aug 2000

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

100 Clinical Results associated with Uridine triphosphate

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100 Translational Medicine associated with Uridine triphosphate

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100 Patents (Medical) associated with Uridine triphosphate

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346

Literatures (Medical) associated with Uridine triphosphate

01 Oct 2024·American Journal of Physiology-Lung Cellular and Molecular Physiology

Mucociliary clearance is impaired in small airways of cystic fibrosis pigs

Article

Author: Hilkin, Brieanna M. ; Sunderland, John J. ; Stewart, Carley G. ; Stoltz, David A. ; Abou Alaiwa, Mahmoud H. ; Dick, David W. ; Gansemer, Nicholas D. ; Zabner, Joseph ; Adam, Ryan J.

We developed a novel positron emission tomography scan assay with unprecedented temporal and spatial resolution to measure mucociliary clearance in the small airways. We proved a long-standing but unproven assertion that mucociliary clearance is inherently abnormal in the small airways of newborn cystic fibrosis piglets that are otherwise free of infection or inflammation. This technique can be easily extended to other airway diseases such as asthma, idiopathic pulmonary fibrosis, or chronic obstructive pulmonary disease.

01 Apr 2024·Brain Research Bulletin

NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at “Zusanli” (ST36)-induced analgesia in ankle arthritis rats

Article

Author: Ding, Guang-Hong ; Xu, Jing-Wen ; Wang, Li-Na ; Shen, Xue-Yong ; Li, Yu-Jia ; Tang, Si-Qi ; Lin, Jie ; Shen, Dan

BACKGROUNDThe efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP.METHODSA 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F₃₄₀/F₃₈₀ ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells.RESULTSThe analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca²⁺]_i rise.CONCLUSIONThese findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

01 May 2023·Journal of thrombosis and thrombolysis

Effects of uridine and nucleotides on hemostasis parameters.

Article

Author: Kilinc, Evren ; Sagdilek, Engin ; Cansev, Mehmet ; Ari, Merve ; Ozluk, Kasim

Several purinergic receptors have been identified on platelets which are involved in hemostatic and thrombotic processes. The aim of the present study was to investigate the effects of uridine and its nucleotides on platelet aggregation and hemostasis in platelet-rich plasma (PRP) and whole blood. The effects of uridine, UMP, UDP, and UTP at different final concentrations (1 to 1000 µM) on platelet aggregation were studied using an aggregometer. In PRP samples, platelet aggregation was induced by ADP, collagen and epinephrine 3 min after addition of uridine, UMP, UDP, UTP and saline (as a control). All thromboelastogram experiments were performed at 1000 µM final concentrations of uridine and its nucleotides in whole blood. UDP and UTP were also tested in thromboelastogram with PRP. Our results showed that UDP, and especially UTP, inhibited ADP- and collagen-induced aggregation in a concentration-dependent manner. In whole blood thromboelastogram experiments, UDP stimulated clot formation while UTP suppressed clot formation. When thromboelastogram experiments were repeated with PRP, UTP's inhibitory effect on platelets was confirmed, while UDP's stimulated clot forming effect disappeared. Collectively, our data showed that UTP inhibited platelet aggregation in a concentration-dependent manner and suppressed clot formation. On the other hand, UDP exhibited distinct effects on whole blood or PRP in thromboelastogram. These data suggest that the difference on effects of UTP and UDP might have arisen from the different receptors that they stimulate and warrant further investigation with regard to their in vivo actions on platelet aggregation and hemostasis.

100 Deals associated with Uridine triphosphate

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lung Cancer	Phase 3	CR	Inspire Pharmaceuticals, Inc.	-
Lung Cancer	Phase 3	-	Merck Serono SA	-
Lung Cancer	Phase 3	CA	Inspire Pharmaceuticals, Inc.	-
Lung Cancer	Phase 3	US	Inspire Pharmaceuticals, Inc.	-
Lung Cancer	Phase 3	CR	Inspire Pharmaceuticals, Inc.	-
Lung Cancer	Phase 3	-	Merck Serono SA	-
Lung Cancer	Phase 3	US	Inspire Pharmaceuticals, Inc.	-
Lung Cancer	Phase 3	CA	Inspire Pharmaceuticals, Inc.	-
Respiratory Tract Infections	Phase 3	-	Kirin Holdings Co., Ltd.	-
Respiratory Tract Infections	Phase 3	-	Merck Serono SA	-