septic

S-Methylisothiourea sulfate ((S)-Methylisothiourea sulfate) is a potent and selective inhibitor of iNOS and exerts beneficial effects in rodent models of septic shock[1].

BD-AcAc 2 (Ketone Ester) is a ketone monoester and can be used as a source of oral nutritional ketones. BD-AcAc 2 can elevate plasma levels of acetoacetate and β-hydroxybutyrate, blood Na+, blood glucose levels and blood creatinine levels after oral administration in mice. BD-AcAc 2 can partly prevent muscle weakness in septic mice. BD-AcAc 2 exhibits potential to improve endurance and exercise performance in animal body. BD-AcAc 2 can also be used to research diabetes or Parkinson's disease.

MEG hemisulfate (Mercaptoethylguanidine hemisulfate) acts as a highly potent and selective suppressor of inducible NO synthase (iNOS), demonstrating EC50 values of 11.5 μM for iNOS, 110 μM for ecNOS, and 60 μM for bNOS in tissue homogenates. It is notably effective as a peroxynitrite scavenger and blocks peroxynitrite-triggered oxidative mechanisms. Furthermore, this compound offers protective benefits across various experimental inflammation prototypes, such as ischemia/reperfusion injury, hemorrhagic shock, periodontitis, inflammatory bowel disease, and both endotoxic and septic shock.

Ethyl gallate (gallic acid ethyl ester) obviously decreases cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner, exhibits cytotoxicity in a dose-dependent manner. Ethyl gallate can inhibit the abilities of invasion of breast cancer in vitro by inhibiting the mRNA levels of MMP-9 MMP-2, phosphorylation of Akt and protein expression of NF-κB and inhibits hydrogen peroxide signaling, may represent an alternative class of vasopressors for use in septic shock. Also, Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K Akt pathway, which may contribute to inhibiting their downstream targets such as NF-κB p-65, Bcl-2 Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells, could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy.

SIRT5 inhibitor 7 (compound 58), a substrate-competitive and selective SIRT5 inhibitor with IC 50 = 310 nM, significantly attenuated renal dysfunction and pathological damage in lipopolysaccharide (LPS)- and cecum ligation perforation (CLP)-induced septic AKI mice, and modulated proteinsuccinimidylation and proinflammatory cytokine release and pro-inflammatory cytokine release in the kidneys of acute kidney injury (AKI) mice.

RNAIII-inhibiting peptide TFA (RNAIII-inhibiting peptide(TFA))(228544-21-6 free base) inhibits S. aureus, effective in the diseases such as cellulitis, keratitis, septic arthritis, osteomylitis and mastitis.

Cl-amidine hydrochloride is an orally available PAD inhibitor that blocks histone 3 deimination and neutrophil extracellular trap formation and improves survival in septic mice. It induces apoptosis in cancer cells and induces miR-16 to cause cell cycle arrest.

Terlipressin Acetate, a highly selective vasopressin V1 receptor agonist, on oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damage in intestinal epithelial cells (IEC-6).Terlipressin acetate exerts anti-inflammatory and anti-oxidative effects. Terlipressin acetate has the potential for hepatorenal syndrome and norepinephrine-resistant septic shock research.

TNF-α IL-1β-IN-1 (compound 11a) is an anti-inflammatory agent that effectively reduces the expression of TNF-α and IL-1β, inhibits oxidative stress and myocardial cell apoptosis, and demonstrates significant activity against septic myocardial injury. Additionally, it improves myocardial blood flow in vivo.

BPD is a COX-2 and TAK1-NF-κB inhibitor with an IC50 of 18.5 μM for COX-2. It suppresses the expression of iNOS, TNF-α, IL-6, and IL-1β at the transcriptional level. BPD possesses anti-inflammatory properties and can inhibit carrageenan-induced paw edema as well as LPS-induced septic death.

Lipid A-11 is a lipid component of endotoxin that is primarily responsible for the toxic properties of gram-negative bacteria. Lipid A-11 constitutes the innermost region of the lipopolysaccharide (LPS) molecule, also known as endotoxin, and its hydrophobic nature facilitates anchoring of the LPS structure into the bacterial outer membrane. Lipid A-11 plays a critical role in host-pathogen interactions, contributing to septic shock and immunological activation during bacterial infections.

(+)-Bicuculline methiodide is a γ-aminobutyric acid type A (GABAA) receptor blocker that crosses the rat blood-brain barrier (BBB) and blocks epileptogens, which can be used to study neurological disorders such as epilepsy. (+)-Bicuculline methiodide reduces liver injury in septic rats.

Tanogitran, a coagulation factor Xa inhibitor, is used potentially for the treatment of septic shock.

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.1It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).2α-MSH (100 pM) reducesS. aureuscolony formation andC. albicansgerm tube formationin vitro.3It inhibits endotoxin-, ceramide-, TNF-α-, or okadaic acid-induced activation of NF-κB in U937 cells.1α-MSH reduces IL-6- or TNF-α-induced ear edema in mice.4It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of α-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.1 1.Catania, A., Airaghi, L., Colombo, G., et al.α-melanocyte-stimulating hormone in normal human physiology and disease statesTrends Endocrinol. Metab.11(8)304-308(2000) 2.Miwa, H., Gantz, I., Konda, Y., et al.Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptorsJ. Pharmacol. Exp. Ther.273(1)367-372(1995) 3.Cutuli, M., Cristiani, S., Lipton, J.M., et al.Antimicrobial effects of a-MSH peptidesJ. Leukoc. Biol.67(2)233-239(2000) 4.Lipton, J.M., Ceriani, G., Macaluso, A., et al.Antiiinflammatory effect of the neuropeptide a-MSH in acute, chronic, and systemic inflammationAnn. N.Y. Acad. Sci.25(741)137-148(1994)

Neuromedin U (NMU) is a neuropeptide first demonstrated to drive smooth muscle contraction.1Translated as a 174 amino acid propeptide, NMU is cleaved to different lengths in different animals. It has diverse receptor-mediated rolesin vivo, as it regulates feeding, vasoconstriction, nociception, and bone remodeling and contributes to obesity, cancer and septic shock.2,2NMU-25 is the active form of NMU in humans. It binds with high affinity to receptors on human left ventricle and coronary artery (KDs = 0.26 and 0.11 nM, respectively), eliciting endothelium-independent vasoconstriction.3NMU-25 also suppresses glucose-stimulated insulin secretion in human islets, and this effect is lost in NMU R165W mutants, resulting in early-onset obesity.4 1.Mitchell, J.D., Maguire, J.J., and Davenport, A.P.Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBritish Journal of Pharmacology15887-103(2009) 2.Greenwood, H.C., Bloom, S.R., and Murphy, K.G.Peptides and their potential role in the treatment of diabetes and obesityRev.Diabet.Stud.8(3)355-368(2011) 3.Mitchell, J.D., Maguire, J.J., Kuc, R.E., et al.Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular systemCardiovascular Research81353-361(2009) 4.Alfa, R.W., Park, S., Skelly, K.R., et al.Suppression of insulin production and secretion by a decretin hormoneCell Metabolism21(2)323-333(2015)

TLR4 inhibitor. Inhibits LPS-induced NF-κB activation in HEK293 cells (IC50 = 2.4 μg/mL). Also inhibits LPS-induced cytokine production and procoagulant effects in PBMCs and HUVECs. Prolongs survival in a mouse septic shock model.

Protein conjugates in tissue regeneration 3 (PCTR3) is a specialized pro-resolving mediator (SPM) synthesized from docosahexaenoic acid . DHA is oxidized to 16S,17S-epoxy-protectin, which is converted to PCTR1 by glutathione S-transferase and to PCTR2 and PCTR3 via peptidases. PCTR3 is found in infected mouse spleens and resolving exudate as well as isolated human spleen and septic plasma. It is also found in both M1 and M2 macrophages differentiated from isolated human monocytes.

LL-37 is a cationic and α-helical antimicrobial peptide expressed in human bone marrow, testis, granulocytes, and gingival epithelium and is upregulated in psoriatic lesions. It inhibits growth of Gram-positive E. coli D21 and Gram-negative B. megatarium in a concentration-dependent manner and LL-37 expression is induced in A549 epithelial cells, alveolar macrophages, neutrophils, and monocyte-derived macrophages following M. tuberculosis infection. LL-37 binds sheep erythrocytes coated with S. minnesota Re-LPS and induces agglutination with a minimal agglutinating concentration (MAC) of 12.1 μg/ml. It is a chemoattractant for, and can induce calcium mobilization in, human monocytes, neutrophils, and T cells that naturally express formyl peptide receptor-like 1 (FPRL1) and FPRL1-transfected HEK293 cells. LL-37 (10-15 μM) pretreatment of dengue virus type 2 (DENV-2) reduces its infectivity as well as levels of viral genomic RNA and NS1 antigen. In vivo, LL-37 inhibits cecal ligation and puncture-induced caspase-1 activation and pyroptosis of peritoneal macrophages, reduces levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α, and improves survival in polybacterial septic mice.

FPL-65447 hydrochloride is a selective D1 receptor agonist that has potential for the acute treatment of renal and cardiac failure and of sepsis and septic shock.

NOS-IN-3 is a potent, selective, imidamide derived NOS inhibitor with an IC 50 against iNOS of 4.6 µM, without inhibiting eNOS . NOS-IN-3 has little toxicity and can be studied in the treatment of inducible isoform involved diseases, such as septic shock .

Ac-FEID-CMK, a potent peptide inhibitor derived from zebrafish-specific GSDMEb, effectively reduces mortality and kidney injury during septic shock by inhibiting pyroptosis and mitigating acute kidney injury (AKI) in vivo. Additionally, it suppresses the caspy2-mediated noncanonical inflammasome pathway [1].

Ac-FEID-CMK TFA is a selective zebrafish GSDMEb-derived peptide inhibitor that reduces mortality and renal injury in infectious shock. It inhibits pyroptosis in vivo, attenuates septic AKI (acute kidney injury), and inhibits the caspy2-mediated atypical inflammatory vesicle pathway.

M62812 (free base), a Toll-like receptor 4 (TLR4) signal transduction inhibitor, suppresses activation of endothelial cells and leukocytes and prevents lethal septic shock in mice. It is utilized in sepsis research [1].

NLRP3-IN-20 (compound 11) is an orally administered inhibitor targeting the NLRP3 inflammasome, exhibiting potent inhibition with an IC50 of 25 nM against IL-1β secretion. It possesses excellent pharmacokinetic properties and has shown significant efficacy in models of non-alcoholic steatohepatitis, fatal septic shock, and colitis [1].