Delving into the Latest Updates on Semapimod Mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Semapimod, Semapimod salt

+ [4]

Target

CRAF x Cytokines

Mechanism

CRAF inhibitors(C-Raf kinase inhibitors), Cytokines inhibitors, Nitric oxide inhibitors

Therapeutic Areas

Immune System DiseasesDigestive System DisordersSkin and Musculoskeletal Diseases+ [3]

Active Indication-

Inactive Indication

Chemotherapy-induced damageCrohn DiseaseHIV Infections+ [3]

Originator Organization

Ferring BV

Active Organization-

Inactive Organization

Cytokine PharmaSciences, Inc.

Ferring Pharmaceuticals A/S

GPC Biotech AG

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC34H52N18O2

InChIKeyPWDYHMBTPGXCSN-UHFFFAOYSA-N

CAS Registry352513-83-8

This study will be conducted in healthy male or female subjects using a double-blind, randomized, placebo-controlled, single-dose design. Up to 30 subjects will be enrolled; 3 healthy subjects in Cohorts 1 and 2 (2 active, 1 placebo) and 8 healthy subjects in Cohorts 3 to 5 (6 active, 2 placebo). The following CPSI-2364 doses are proposed: 1 mg, 10 mg, 30 mg, 90 mg, and 270 mg.Safety will be evaluated throughout the study and include physical examinations, vital signs assessments, 12-lead electrocardiograms (ECGs), routine clinical laboratory tests (including blood chemistry, hematology, coagulation, and urinalysis), and adverse event (AE) assessments. Vital sign assessments and 12-lead ECGs will be performed repeatedly over the 24-hour observation period. Venous blood samples will be taken at specified intervals and tested for the presence of CPSI-2364.

Start Date01 Jul 2009

Sponsor / Collaborator

Ferring Pharmaceuticals A/S

NCT00741910 / CompletedPhase 2

Extension Study of CNI-1493 for Treatment of Moderate to Severe Crohn's Disease

Study CNI-1493-CD06 is an open, single-arm extension studies to CD03 and CD05. CDAI is the only efficacy measure assessed in this study. The safety of multiple courses of semapimod is to be determined by the incidence of clinical and laboratory adverse events.

Start Date01 Jul 2003

Sponsor / Collaborator

Ferring Pharmaceuticals A/S

NCT00740103 / CompletedPhase 2

Long-term Study of Semapimod (CNI-1493) for Treatment of Moderate to Severe Crohn's Disease With Reference to Study CNI-1493-CD-04, 1 or 3 Days' Treatment vs. Placebo

CNI-1493-CD05 is an open-label extension study of CNI-1493-CD04. In the CD05 study, patients are eligible for up to 5 courses of semapimod 60 mg IV x 3 days every 6 - 8 weeks. Primary objective is assessment of the efficacy of cumulative doses of semapimod measured by decrease in Crohn's Disease Activity Index (CDAI).

Start Date01 Dec 2002

Sponsor / Collaborator

Ferring Pharmaceuticals A/S

100 Clinical Results associated with Semapimod Mesylate

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100 Translational Medicine associated with Semapimod Mesylate

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100 Patents (Medical) associated with Semapimod Mesylate

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91

Literatures (Medical) associated with Semapimod Mesylate

01 Apr 2024·Cell Chemical Biology

Discovery of antibiotics that selectively kill metabolically dormant bacteria

Article

Author: Wong, Felix ; Bandyopadhyay, Parijat ; Zheng, Erica J ; Lourido, Sebastian ; Anahtar, Melis N ; Valeri, Jacqueline A ; Stokes, Jonathan M ; Schulte, Fabian ; Linnehan, Brooke ; Renner, Lars D ; Herneisen, Alice ; Krishnan, Aarti ; Andrews, Ian W ; Collins, James J

There is a need to discover and develop non-toxic antibiotics that are effective against metabolically dormant bacteria, which underlie chronic infections and promote antibiotic resistance. Traditional antibiotic discovery has historically favored compounds effective against actively metabolizing cells, a property that is not predictive of efficacy in metabolically inactive contexts. Here, we combine a stationary-phase screening method with deep learning-powered virtual screens and toxicity filtering to discover compounds with lethality against metabolically dormant bacteria and favorable toxicity profiles. The most potent and structurally distinct compound without any obvious mechanistic liability was semapimod, an anti-inflammatory drug effective against stationary-phase E. coli and A. baumannii. Integrating microbiological assays, biochemical measurements, and single-cell microscopy, we show that semapimod selectively disrupts and permeabilizes the bacterial outer membrane by binding lipopolysaccharide. This work illustrates the value of harnessing non-traditional screening methods and deep learning models to identify non-toxic antibacterial compounds that are effective in infection-relevant contexts.

20 Apr 2023·Pharmaceutics

Multicomponent Lipid Nanoparticles for RNA Transfection.

Article

Author: Gretskaya, Nataliya ; Fomina-Ageeva, Elena ; Andreev, Dmitry ; Bezuglov, Vladimir ; Mikhalyov, Ilya ; Vodovozova, Elena ; Zinchenko, Galina ; Zalygin, Anton ; Akimov, Mikhail ; Belitskaya, Ekaterina

Despite the wide variety of available cationic lipid platforms for the delivery of nucleic acids into cells, the optimization of their composition has not lost its relevance. The purpose of this work was to develop multi-component cationic lipid nanoparticles (LNPs) with or without a hydrophobic core from natural lipids in order to evaluate the efficiency of LNPs with the widely used cationic lipoid DOTAP (1,2-dioleoyloxy-3-[trimethylammonium]-propane) and the previously unstudied oleoylcholine (Ol-Ch), as well as the ability of LNPs containing GM3 gangliosides to transfect cells with mRNA and siRNA. LNPs containing cationic lipids, phospholipids and cholesterol, and surfactants were prepared according to a three-stage procedure. The average size of the resulting LNPs was 176 nm (PDI 0.18). LNPs with DOTAP mesylate were more effective than those with Ol-Ch. Core LNPs demonstrated low transfection activity compared with bilayer LNPs. The type of phospholipid in LNPs was significant for the transfection of MDA-MB-231 and SW 620 cancer cells but not HEK 293T cells. LNPs with GM3 gangliosides were the most efficient for the delivery of mRNA to MDA-MB-231 cells and siRNA to SW620 cells. Thus, we developed a new lipid platform for the efficient delivery of RNA of various sizes to mammalian cells.

15 Jun 2016·The Journal of ImmunologyQ2 · MEDICINE

Experimental Anti-Inflammatory Drug Semapimod Inhibits TLR Signaling by Targeting the TLR Chaperone gp96

Q2 · MEDICINE

Article

Author: Wang, Jin ; Grishin, Anatoly V. ; Ford, Henri R.

AbstractSemapimod, a tetravalent guanylhydrazone, suppresses inflammatory cytokine production and has potential in a variety of inflammatory and autoimmune disorders. The mechanism of action of Semapimod is not well understood. In this study, we demonstrate that in rat IEC-6 intestinal epithelioid cells, Semapimod inhibits activation of p38 MAPK and NF-κB and induction of cyclooxygenase-2 by TLR ligands, but not by IL-1β or stresses. Semapimod inhibits TLR4 signaling (IC50 ≈0.3 μmol) and acts by desensitizing cells to LPS; it fails to block responses to LPS concentrations of ≥5 μg/ml. Inhibition of TLR signaling by Semapimod is almost instantaneous: the drug is effective when applied simultaneously with LPS. Semapimod blocks cell-surface recruitment of the MyD88 adapter, one of the earliest events in TLR signaling. gp96, the endoplasmic reticulum–localized chaperone of the HSP90 family critically involved in the biogenesis of TLRs, was identified as a target of Semapimod using ATP-desthiobiotin pulldown and mass spectroscopy. Semapimod inhibits ATP-binding and ATPase activities of gp96 in vitro (IC50 ≈0.2–0.4 μmol). On prolonged exposure, Semapimod causes accumulation of TLR4 and TLR9 in perinuclear space, consistent with endoplasmic reticulum retention, an anticipated consequence of impaired gp96 chaperone function. Our data indicate that Semapimod desensitizes TLR signaling via its effect on the TLR chaperone gp96. Fast inhibition by Semapimod is consistent with gp96 participating in high-affinity sensing of TLR ligands in addition to its role as a TLR chaperone.

100 Deals associated with Semapimod Mesylate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Semapimod Mesylate	-	DB12094

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Crohn Disease	Phase 2	US	Ferring Pharmaceuticals A/S	01 Jun 2002
HIV Infections	Phase 2	DE	GPC Biotech AG	-
Pancreatitis	Phase 2	NL	Cytokine PharmaSciences, Inc.	-
Psoriasis	Phase 2	US	Cytokine PharmaSciences, Inc.	-
Crohn Disease	Discovery	US	Ferring Pharmaceuticals A/S	01 Jun 2002
Chemotherapy-induced damage	Discovery	US	Cytokine PharmaSciences, Inc.	-
Inflammation	Discovery	US	Cytokine PharmaSciences, Inc.	-