Page last updated: 2024-11-11

semapimod

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

semapimod: macrophage-deactivating agent used to treat experimental autoimmune encephalomyelitis in mice; prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID5745214
CHEMBL ID2107779
SCHEMBL ID12201344
SCHEMBL ID18758868
MeSH IDM0461841

Synonyms (27)

Synonym
n,n'-bis(3-acetylphenyl)decane diamide tetrakis (amidinohydrazone)
semapimod
cni-1493
n,n'-bis(3,5-bis{(1e)-n-[amino(imino)methyl]ethanehydrazonoyl}phenyl)decanediamide
axd455
n,n'-bis[3,5-bis[(e)-n-guanidino-c-methyl-carbonimidoyl]phenyl]decanediamide
cpsi 2364
cpsi-2364 free base
axd-455
n,n'-bis(3,5-bis(1-(carbamimidoylhydrazono)ethyl)phenyl)decanediamide
n,n'-bis[3,5-bis[(e)-n-(diaminomethylideneamino)-c-methylcarbonimidoyl]phenyl]decanediamide
semapimod [inn]
9sgw2h1k8p ,
352513-83-8
n,n'-bis{3,5-bis(1-(carbamimidoylhydrazono)ethyl)phenyl}decanediamide
unii-9sgw2h1k8p
n,n'-bis(3,5-bis(1- (carbamimidoylhydrazono)ethyl)phenyl)decanediamide
CHEMBL2107779
SCHEMBL12201344
SCHEMBL18758868
NCGC00487056-01
DB12094
n1,n10-bis(3,5-bis(1-(2-carbamimidoylhydrazono)ethyl)phenyl)decanediamide
EN300-261068
n,n'-bis({3,5-bis[1-(carbamimidamidoimino)ethyl]phenyl})decanediamide
CS-0006827
HY-15509

Research Excerpts

Overview

Semapimod is a synthetic guanylhydrazone that inhibits the mitogen-activated protein kinase (MAPK) pathway, macrophage activation, and the production of several inflammatory cytokines.

ExcerptReferenceRelevance
"Semapimod is an experimental drug that strongly inhibits macrophages and stimulates the cholinergic anti-inflammatory pathway. "( Semapimod a new pretreatment modality of acute intestinal ischemia-reperfusion syndrome: experimental study in rabbits.
Kallaitzopoulou, ME; Kontopoulou, KE; Kosmidou, EK; Kotakidou, RE; Papadimitriou, DK; Pitoulias, GA; Vlachakis, IK, 2011
)
3.25
"Semapimod is a synthetic guanylhydrazone that inhibits the mitogen-activated protein kinase (MAPK) pathway, macrophage activation, and the production of several inflammatory cytokines."( Pre-ERCP infusion of semapimod, a mitogen-activated protein kinases inhibitor, lowers post-ERCP hyperamylasemia but not pancreatitis incidence.
Bruno, MJ; de Vos, AF; Dijkgraaf, MG; Fockens, P; Hommes, D; Powers, BL; Rauws, EA; van der Poll, T; van Westerloo, DJ, 2008
)
1.39

Treatment

Semapimod treatment led to a significant decrease of p38-MAPK phosphorylation in macrophages. Proinflammatory gene expression of macrophage inflammatory protein-1alpha was also reduced.

ExcerptReferenceRelevance
"Semapimod treatment led to a significant decrease of p38-MAPK phosphorylation in macrophages; proinflammatory gene expression of macrophage inflammatory protein-1alpha, interleukin-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1; and neutrophil infiltration."( Inhibition of p38 mitogen-activated protein kinase pathway as prophylaxis of postoperative ileus in mice.
de la Cruz, VF; Hirner, A; Kalff, JC; Pantelis, D; Sielecki, T; Straesser, S; Vilz, TO; Wehner, S, 2009
)
1.07
"Both Semapimod and vehicle treatments were administered by daily tail vein injections over a course of five days."( Macrophage inhibitor, semapimod, reduces tumor necrosis factor-alpha in myocardium in a rat model of ischemic heart failure.
Burkhoff, D; Fal, JM; Gu, A; Homma, S; Kherani, AR; Moss, GW; Oz, MC; Plasse, T; Rui, L; Schulman, AR; Sorabella, R; Wang, J; Zhang, G; Zhou, H, 2004
)
1.09
"pre-treatment with semapimod (1 µg·kg(-1) ) or saline."( Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus.
Bennink, RJ; Boeckxstaens, GE; Buijs, RM; Cailotto, C; de Jonge, WJ; The, F; van der Vliet, J, 2011
)
0.69

Compound-Compound Interactions

ExcerptReferenceRelevance
" In combination with high-dose IL-2, CNI-1493 at > or = 25 mg/m2 seemed to exacerbate IL-2-induced nephrotoxicity: grade 3 or 4 creatinine increases developed in 3 of 6 patients at 25 or 32 mg/m2, as compared with 1 of 16 patients at doses < or = 16 mg/m2."( A phase I study of CNI-1493, an inhibitor of cytokine release, in combination with high-dose interleukin-2 in patients with renal cancer and melanoma.
Atkins, MB; Gollob, J; MacPherson, BL; Mier, J; Plasse, T; Redman, B; Sosman, J; Weber, J, 2001
)
0.31

Bioavailability

ExcerptReferenceRelevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

ExcerptRelevanceReference
" In vivo application of this substance in Plasmodium berghei ANKA-infected C57BL/6 mice significantly reduced parasitemia after dosage of 1 mg/kg or 4 mg/kg/body weight and prevented death of mice with cerebral malaria."( The guanylhydrazone CNI-1493: an inhibitor with dual activity against malaria-inhibition of host cell pro-inflammatory cytokine release and parasitic deoxyhypusine synthase.
Bevec, D; Görbig, UF; Hauber, I; Hauber, J; Hoerauf, A; Kaiser, A; Meier, C; Sarite, SR; Specht, S, 2008
)
0.35
"Single and 3 day dosing of semapimod (< or = 180 mg) was ineffective for the treatment of moderate to severe CD."( A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease.
Bar-Meir, S; Bokemeyer, B; Buchman, AL; Dotan, I; Eliakim, R; Goldin, E; Hoffman, JC; Hommes, D; Homoky, D; Kornbluth, A; Maaser, C; Mahadevan, U; Plasse, T; Powers, B; Rachmilewitz, D; Rutgeerts, P; Schreiber, S; Seidler, U; van der Woude, CJ, 2010
)
0.9
" Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI."( The novel orally active guanylhydrazone CPSI-2364 prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling.
Hong, GS; Kalff, JC; Lysson, M; Pantelis, D; Sielecki, T; Sommer, N; Stoffels, B; Vilz, TO; Wehner, S, 2012
)
0.38
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (5)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (80)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's22 (27.50)18.2507
2000's36 (45.00)29.6817
2010's20 (25.00)24.3611
2020's2 (2.50)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 23.29

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index23.29 (24.57)
Research Supply Index4.48 (2.92)
Research Growth Index4.44 (4.65)
Search Engine Demand Index26.67 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (23.29)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials4 (4.82%)5.53%
Reviews5 (6.02%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other74 (89.16%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (5)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Extension Study of CNI-1493 for Treatment of Moderate to Severe Crohn's Disease [NCT00741910]Phase 215 participants (Actual)Interventional2003-07-31Completed
A Phase 1, Single Center, Randomized, Double-Blind, Placebo-Controlled Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetic Profiles of Oral CPSI-2364 in Healthy Subjects [NCT00950105]Phase 130 participants (Actual)Interventional2009-07-31Completed
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 [NCT00740103]Phase 2119 participants (Actual)Interventional2002-12-31Completed
A Randomized, Double-Blind, Placebo-controlled Study of CNI-1493 for Treatment of Moderate to Severe Crohn's Disease [NCT00038766]Phase 233 participants (Actual)Interventional2002-06-30Terminated(stopped due to Unable to enroll into study.)
A Randomized, Double-Blind, Placebo-controlled Study of CNI-1493 for Treatment of Moderate to Severe Crohn's Disease 1 or 3 Days' Treatment vs. Placebo [NCT00739986]Phase 2152 participants (Actual)Interventional2002-10-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]