Delving into the Latest Updates on Decitabine/Tetrahydrouridine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Eclipse, NDec, Tetrahydrouridine/decitabine

+ [2]

Target

CDA x DNMT1

Mechanism

CDA inhibitors(Cytidine deaminase inhibitors), DNMT1 inhibitors(DNA (cytosine-5)-methyltransferase 1 inhibitors)

Therapeutic Areas

Congenital DisordersHemic and Lymphatic DiseasesOther Diseases

Active Indication

Anemia, Sickle Cell

Inactive Indication-

Originator Organization

Epic Destiny, Inc

Active Organization

Novo Nordisk A/S

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC17H28N6O10

InChIKeyXKGWHDNFUIJPAH-RLTXCRDUSA-N

CAS Registry1394942-06-3

This study will look at two different oral formulations and compare them. The medicine in the study is called NDec and it is a combination of two medicines (decitabine and tetrahydrouridine). Both medicines are new for the treatment of sickle cell disease, a rare blood disease. The purpose of the study is to compare the absorption of two different NDec versions (a tablet and a capsule). Participant will either get first the tablet and then the capsule, or the other way around. The order in which participant get them is decided by chance. The study will last for about 12 to 45 days depending on the wash-out period between the two stays in the clinic and from recruitment to the first study day.

Start Date27 Feb 2024

Sponsor / Collaborator

Novo Nordisk A/S

NCT05405114 / RecruitingPhase 2

A Multicentre Trial Evaluating the Efficacy and Safety of Oral Decitabine Tetrahydrouridine (NDec) in Patients With Sickle Cell Disease

This study examines how well a new, potential medicine called NDec works and is tolerated in people with sickle cell disease. NDec is a combination of two medicines (decitabine-tetrahydrouridine). Both medicines are new for the treatment of sickle cell disease. Participants who are not taking Hydroxyurea (HU) will get NDec, NDec and placebo, or placebo. Participants who are on HU treatment before joining the study will get NDec, NDec and placebo, or continue on HU. Which treatment participants get is decided by chance. Participants getting NDec and/or Placebo will get capsules to take twice weekly. The study will last for about a year.

Start Date07 Jul 2022

Sponsor / Collaborator

Novo Nordisk A/S

100 Clinical Results associated with Decitabine/Tetrahydrouridine

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100 Translational Medicine associated with Decitabine/Tetrahydrouridine

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100 Patents (Medical) associated with Decitabine/Tetrahydrouridine

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38

Literatures (Medical) associated with Decitabine/Tetrahydrouridine

01 Nov 2024·Microbial Pathogenesis

Epinecidin-1 and lactic acid synergistically inhibit Aeromonas hydrophila through membrane disruption

Article

Author: Wang, Yang ; Li, Yanzi ; Li, Shufang ; Luo, Yun-Long ; Wang, Yang ; Li, Yanzi ; Wei, Hongshuo ; Zhang, Guangchen ; Bai, Dong-Qing ; Wang, Jing-Ru

Epinecidin-1 (Epi-1) is an antimicrobial peptide originated from fish with various pharmacological activities but carries the risk of acquiring resistance with long-term use. In the present study, we use L-lactic acid to enhance the antibacterial activity of synthesized Epi-1 against the aquaculture and food pathogen Aeromonas hydrophila. The results showed that 5.5 mmol/L lactic acid increased the inhibitory and bactericidal activity of 25 μmol/L Epi-1 against two strains of A. hydrophila. The laser confocal images proved that lactic acid pre-treatment improved the attachment efficiency of Epi-1 in A.hydrophila cells. In addition, lactic acid enhanced the damaging effect of Epi-1 on the cell membrane of A. hydrophila, evidenced by releasing more nucleic acids, proteins, and transmembrane pH ingredients decrease and electromotive force dissipation. SEM images showed that compared with the single Epi-1 treatment, the co-treatment of Epi-1 and lactic acid caused more outer membrane vesicles (OMVs) and more severe cell deformation. These findings proved that lactic acid could enhance the efficiency of Epi-1 against A. hydrophila and shed light on new aspects to avoid resistance of pathogens against Epi-1.

01 Oct 2023·Journal of pharmaceutical sciences

In Vitro Interaction of Tetrahydrouridine with Key Human Nucleoside Transporters.

Article

Author: Klukovits, Anna ; Koncsos, Gábor ; Säll, Carolina

NDec is a novel combination of oral decitabine and tetrahydrouridine that is currently under clinical development for the treatment of sickle cell disease (SCD). Here, we investigate the potential for the tetrahydrouridine component of NDec to act as an inhibitor or substrate of key concentrative nucleoside transporters (CNT1-3) and equilibrative nucleoside transporters (ENT1-2). Nucleoside transporter inhibition and tetrahydrouridine accumulation assays were performed using Madin-Darby canine kidney strain II (MDCKII) cells overexpressing human CNT1, CNT2, CNT3, ENT1, and ENT2 transporters. Results showed that tetrahydrouridine did not influence CNT- or ENT-mediated uridine/adenosine accumulation in MDCKII cells at the concentrations tested (25 and 250 µM). Accumulation of tetrahydrouridine in MDCKII cells was initially shown to be mediated by CNT3 and ENT2. However, while time- and concentration-dependence experiments showed active accumulation of tetrahydrouridine in CNT3-expressing cells, allowing for estimation of K_m (3,140 µM) and V_max (1,600 pmol/mg protein/min), accumulation of tetrahydrouridine was not observed in ENT2-expressing cells. Potent CNT3 inhibitors are a class of drugs not generally prescribed to patients with SCD, except in certain specific circumstances. These data suggest that NDec can be administered safely with drugs that act as substrates and inhibitors of the nucleoside transporters included in this study.

01 Sep 2023·Food Science & Nutrition

Epinecidin‐1 (an active marine antimicrobial peptide): Effects on the survival of inoculated Escherichia Coli O157:H7 And Staphylococcus aureus bacteria, antioxidant, and sensory attributes in raw milk

Article

Author: Salimnejhad, Ziba ; Hassanzadazar, Hassan ; Aminzare, Majid

AbstractThis study aimed to evaluate the effects of Epinecidin‐1 (Epi‐1) on total viable count (TVC), total psychrotrophic count (TPC), sensory attributes, and the survival of Escherichia Coli O157:H7 and Staphylococcus aureus bacteria inoculated in pasteurized milk samples during cold storage (4°C). Four treatments of milk samples were prepared including milk samples containing three concentrations of Epi‐1 (0.0025, 0.005, and 0.01%) and control (without Epi‐1). The treated milk samples were evaluated in vitro (minimum inhibitory concentration, Minimum bactericidal concentration, disk diffusion test, DPPH, reducing power assays) and in vivo (TVC, TPC, sensory properties, and enumeration of inoculated E. coli and S. aureus) during 9 days at cold storage. The best antibacterial and antioxidant power of Epi‐1 was observed at a concentration of 0.01%. Based on the MICs and MBCs, the most susceptible and resistant bacteria to Epi‐1 were B. cereus and S. aureus strains, respectively. The DPPH scavenging potential of Epi‐1 was in the range of 77%–80%. Treated samples containing 0.01% Epi‐1 had the lowest TVC and TPC and reached 3.9 and 2.96 CFU log/mL at the end day of storage. A decrease of 6 and 1.4 logs CFU/g of E. coli O157:H7 and S. aureus was seen in all treatments containing Epi‐1, respectively, on the last day of storage period. There are no unpleasant sensory properties in treated samples with Epi‐1. Our results indicate that Epi‐1 has good potential as a bio‐preservative to prevent raw milk spoilage and reduction of milk‐borne pathogens.

100 Deals associated with Decitabine/Tetrahydrouridine

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Anemia, Sickle Cell	Phase 2	CA	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	LB	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	GR	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	US	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	IN	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	ZA	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	ES	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	IT	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	TR	Novo Nordisk A/S	07 Jul 2022
Anemia, Sickle Cell	Phase 2	FR	Novo Nordisk A/S	07 Jul 2022