septic

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.

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.

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.

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.

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)

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.

D359-0396 is an orally active NLRP3 inflammasome inhibitor that mitigates pyroptosis and reduces IL-1β release in macrophages by inhibiting the oligomerization of NLRP3, ASC, and the cleavage of GSDMD. This compound is effective in alleviating Experimental Autoimmune Encephalomyelitis (EAE) and enhances survival following septic shock in mice [1].

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 .

(+)-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.

SIRT5 Inhibitor 6 is a potent, selective, and substrate-competitive inhibitor of SIRT5, exhibiting an IC50 of 3.0 μM, and demonstrates therapeutic potential for treating septic acute kidney injury (AKI) in vivo [1].

Enibarcimab is a humanized murine monoclonal immunoglobulin G1 (IgG1) antibody, potentially applicable in the research of acute heart failure, COVID-19 infections, and septic shock [1].

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].

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].

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.

Ginsenoside Rg4 is a natural product

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)

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.

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.

HMGB1-IN-2 (compound 15) is a selective inhibitor of the highly conserved nuclear protein HMGB1, demonstrating no inhibitory effect at an IC50 of 20.2 μM in RAW264.7 cells. At a concentration of 30 μM, HMGB1-IN-2 reduces IL-1β, TNF-α, and caspase-1 p20 levels, and inhibits NF-κB p65 phosphorylation, providing anti-apoptotic effects. In vivo, HMGB1-IN-2 at a dose of 15 mg/kg administered intraperitoneally alleviates kidney injury in a mouse model of septic acute kidney injury. Furthermore, it inhibits Huh7 and A549 cells with IC50 values of 77.0 μM and 82.0 μM, respectively [1].

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

Emodin 6-O-β-D-glucoside (Glucoemodin) can protect barrier integrity and inhibit HMGB1-mediated inflammatory responses, which suggests a potential use as a therapy for sepsis or septic shock. Emodin 6-O-beta-D-glucoside has anti-inflammatory activities and also may have significant therapeutic benefits against diabetic complications and atherosclerosis.

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].

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.

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].

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