Delving into the Latest Updates on UR-1505 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

Cytokines inhibitors, NFATC1 inhibitors(Nuclear factor of activated T-cells cytoplasmic 1 inhibitors), Lymphocytes inhibitors

Therapeutic Areas

Immune System DiseasesCongenital DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication-

Inactive Indication

Dermatitis, AtopicGraft RejectionInflammatory Bowel Diseases+ [2]

Originator Organization

Palau Pharma SA

Active Organization-

Inactive Organization

Palau Pharma SA

Noucor Health SA

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC10H7F5O4

InChIKeyBLEWPNAUDGZWPU-UHFFFAOYSA-N

CAS Registry651331-92-9

PURPOSEUR-1505 is a new small molecule with immune modulator properties intended for the topical treatment of inflammatory skin diseases that has shown anti-inflammatory effects in models of skin inflammation. We compared the activity of UR-1505 ointment against its vehicle in the treatment of atopic dermatitis. Secondary objectives included exploring dose response, safety, and local tolerability of UR-1505.METHODSPatients with AD lesions on 2 symmetrical topographic areas (arms, leg, or trunk) were included in this unicenter randomized, double-blind, within-patient, controlled Phase II exploratory trial and received simultaneously 2 different treatments (0.5%, 1%, or 2% UR-1505 and vehicle or 0.1% tacrolimus ointment) once daily during 28 days. The primary efficacy end point was the change from baseline in the Investigator Global Assessment score at Day 28. Secondary end points were percentage of area clearance, local Eczema Area Severity Index (local EASI), and local tolerability. A linear mixed model was used, fitting treatment, body side, and group (treatment at the contralateral side) as fixed factors and the patient as a random effect.FINDINGSTwenty-eight patients were randomized and 25 patients were included in the per protocol analysis, with 50 evaluable lesions (n = 13 for vehicle, n = 8 for UR-1505 0.5%, n = 9 for 1% UR-1505, n=8 for 2% UR-1505, and n=12 for tacrolimus). The mean Investigator Global Assessment score change from baseline at Day 28 was -1.7 for vehicle, -1.0, -1.2, and -1.5 for 0.5%, 1%, and 2% UR-1505, respectively, and -2.6% for tacrolimus (P = 0.002). No serious nor causal adverse reactions were reported in this study, but patients reported numerous local symptoms after product applications, especially itching, tingling, tightness, and heat/burning sensations at frequencies that were similar for vehicle, 1% UR-1505, and 2% UR-1505; more frequent with 0.5% UR-1505; and lowest for tacrolimus.IMPLICATIONSThis study found that UR-1505 may not be a suitable option for the treatment of atopic dermatitis due to its lack of clinically relevant effect compared with its vehicle and 0.1% tacrolimus ointment.

01 Jan 2009·Journal of Pharmacological SciencesQ3 · MEDICINE

The New Salicylate Derivative UR-1505 Modulates the Th2/Humoral Response in a Dextran Sodium Sulphate Model of Colitis That Resembles Ulcerative Colitis

Q3 · MEDICINE

ArticleOA

Author: Julio Gálvez ; Isabel Ramis ; Antonio Zarzuelo ; Mònica Comalada ; Juan Román ; Manuel Merlos ; Dolors Balsa ; Pedro Michelena ; Elvira Bailón

The aim of the present study was to evaluate the inmunomodulatory effects of UR-1505, a new salicylate derivative, on the T helper (Th)2/humoral response produced during dextran sodium sulfate (DSS)-induced rat colitis. In the in vitro studies, UR-1505 (300 microM) inhibited both the production of interleukin (IL)-10 and IL-5 in concanavalin A (Con A)-activated splenocytes and the production of immunoglobulin (Ig) G and IgA by B-lymphocytes. However, in contrast to the in vitro results, the administration of UR-1505 (10 and 30 mg/kg per day) to rats with established DSS-colitis enhanced both IL-10 and IgA production, whereas it inhibited IgG production, thus ameliorating the intestinal inflammation.

01 Nov 2007·Biochemical PharmacologyQ2 · MEDICINE

The intestinal anti-inflammatory effects of the novel agent UR-1505 in the TNBS model of rat colitis are mediated by T-lymphocyte inhibition

Q2 · MEDICINE

Article

Author: Angel Concha ; Juan Román ; Ana Nieto ; Alberto Fernández de Arriba ; Desirée Camuesco ; Antonio Zarzuelo ; Julio Gálvez ; Mònica Comalada ; Elvira Bailón ; Manuel Merlos ; Isabel Ramis

UR-1505 is a novel pentafluoropropoxy derivative of salicylic acid, selected from a series of salicylate derivatives, according to their activity as inhibitors of T-lymphocyte activation. This study describes the anti-inflammatory activity of UR-1505 on trinitrobenzenesulphonic acid-induced colitis in rat, an experimental model that resembles to Crohn's disease (CD), as well as its in vitro effects on T-cells and bone marrow-derived macrophages (BMDM) activation. UR-1505 showed intestinal anti-inflammatory effect, associated with reduced colonic levels of TNFalpha and LTB(4), inhibition of the expression of IFNgamma and iNOS, and lower colonic leukocyte infiltration. The in vitro assays revealed that UR-1505 also inhibited T-lymphocyte proliferation and IL-12/IFNgamma production, two of the main pro-inflammatory cytokines involved in the pathogenesis of CD. However, UR-1505 did not modify LPS- nor IFNgamma-induced activation in BMDM. Thus, UR-1505 specifically affects T-cells without modifying the activation of BMDM. In conclusion, the intestinal anti-inflammatory activity of UR-1505 seems to be mediated by a reduction in the recruitment of immune cells to the inflammatory foci, together with the inhibition of T-cell activation. These results suggest that UR-1505 may be an interesting candidate to be explored for the treatment of CD.

100 Deals associated with UR-1505

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dermatitis, Atopic	Phase 2	FR	Palau Pharma SA	-
Dermatitis, Atopic	Phase 2	-	Noucor Health SA	-
Dermatitis, Atopic	Phase 2	ES	Palau Pharma SA	-
Graft Rejection	Phase 2	ES	Palau Pharma SA	-
Inflammatory Bowel Diseases	Phase 2	ES	Palau Pharma SA	-
Psoriasis	Phase 2	ES	Palau Pharma SA	-
Psoriasis	Phase 2	-	Noucor Health SA	-
Rheumatoid Arthritis	Phase 2	ES	Palau Pharma SA	-