sepsis

Acetylcholine Chloride is the chloride salt form of acetylcholine, a synthetic, quaternary amino alcohol with cholinergic properties. Acetylcholine chloride (Pilofrin) mimics the parasympathomimetic effect of the endogenous compound acetylcholine. Administered as an ophthalmic solution, this drug stimulates the cholinoceptors in the sphincter muscle of the iris, causing the pupil to constrict.

Fosfomycin calcium (Phosphomycin calcium salt) is a blood-brain barrier penetrating, broad-spectrum antibiotic by irreversibly inhibiting an early stage in cell wall synthesis.

An antibiotic produced by Streptomyces fradiae.

Fosfomycin sodium is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis.

Dicloxacillin Sodium hydrate is a narrow-spectrum β-Lactam antibiotic of the penicillin class, used to treat infections caused by susceptible Gram-positive bacteria.

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.

L48H37 is a chemically stable analog of Curcumin. It exhibits potent inhibitory properties against myeloid differentiation protein 2 (MD2), acting as a specific inhibitor. Its mechanism involves inhibiting the interaction and signaling transduction of LPS-TLR4/MD2. L48H37 is primarily utilized in sepsis and lung injury research [1].

Tamarixetin (4'-O-Methyl Quercetin) is a natural flavonoid derivative of quercetin exhibiting multi-target biological activities including anti-inflammatory, antioxidant, antitumor, neuroprotective, and cardiovascular protective effects. Tamarixetin exerts its biological activity through multiple mechanisms such as direct radical scavenging, signaling pathway regulation, enzyme inhibition, and receptor binding.

Torbafylline, a xanthine derivative, is a phosphodiesterase (PDE) inhibitor that attenuates burn-induced protein hydrolysis in rat skeletal muscle through activation of the PDE4/cAMP/EPAC/PI3K/Akt pathway, and inhibits the enhanced ubiquitin-proteasome-dependent protein hydrolysis in skeletal muscle of cancer- and sepsis-prone rats.

Docetaxel trihydrate (RP-56976 Trihydrate) is an antineoplastic agent that has a unique mechanism of action as an inhibitor of cellular mitosis and that currently plays a central role in the therapy of many solid tumor including breast and lung cancer. Therapy with docetaxel has been associated with a low rate of serum enzyme elevations and rarely to instances of acute hepatic necrosis generally due to severe hypersensitivity reactions or sepsis.

Dexmedetomidine hydrochloride (Precedex) is a potent, selective, orally active α2-adrenoceptor agonist with a Ki value of 1.08 nM. It shows 1620-fold selectivity over α1-adrenoceptors. Dexmedetomidine hydrochloride (Precedex) can protect against sepsis-induced acute lung injury through anti-inflammatory, anti-oxidative, and anti-apoptotic effects.

Isoegomaketone is a sesquiterpenoid isolated from the essential oil of Perilla frutescens. It exhibits a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-cancer, anti-mycobacterial, anti-arthritic, and anti-obesity effects. In immune modulation, it effectively suppresses the production of pro-inflammatory mediators. In the field of anti-infection, it has emerged as a potential novel inhibitor against drug-resistant pathogens such as Mycobacterium abscessus.

SIRT5 inhibitor 6 is a novel and potent Sirtuin 5 inhibitor with an IC50 = 310 nM for the treatment of sepsis-associated acute kidney injury (AKI) that modulates protein succinylation and pro-inflammatory cytokine release in the kidney and attenuates renal dysfunction and pathologic injury.

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.

Cl-amidine TFA is an orally active PAD inhibitor with IC₅₀ values of 0.8 μM, 6.2 μM and 5.9 μM for PAD1, PAD3 and PAD4, respectively. This compound can induce cancer cell apoptosis, and also upregulate the expression of miR-16 (miRNA-16, microRNA-16), thereby triggering cell cycle arrest. In addition, Cl-amidine TFA can block the citrullination of histone 3 and the formation of neutrophil extracellular traps, effectively improving the survival rate of mice with sepsis.

Norvancomycin hydrochloride (Desmethyl-vancomycin hydrochloride) is used as a treatment for endocarditis, osteomyelitis, pneumonia, sepsis, or soft tissue infections caused by Staphylococcus.

NU6300 is an inhibitor of the first covalent ATP-competitive CDK2.

Antimicrobial agent-34 (compound 4h), characterized by its clogP value of 9.14, effectively disrupts the integrity of bacterial cell membranes. This compound boasts a minimum inhibitory concentration (MIC) ranging from 1–4 μg/mL and shows notable plasma stability with an HC50 of 131.1 μg/mL. Additionally, it exhibits excellent membrane selectivity, as evidenced by its HC50/MIC ratio of 65.6, and possesses rapid sterilization capabilities. It not only increases intracellular reactive oxygen species but also causes the leakage of protein and DNA, culminating in bacterial death. Antimicrobial agent-34 has demonstrated significant antibacterial effectiveness in vivo, particularly in a mouse sepsis model infected with Staphylococcus aureus ATCC43300.

1-(Isothiazol-3-yl)ethan-1-one (Q11) is an inhibitor of CYP2E1. This compound is utilized in research related to rheumatoid arthritis and sepsis.

TH023 is an inhibitor of the TLR4 signaling pathway, specifically targeting the formation of TLR4 homodimers. In HEK-Blue hTLR4 cells, TH023 suppresses the secretion of embryonic alkaline phosphatase with an IC50 of 0.354 μM and inhibits NO expression in RAW264.7 cells, with an IC50 of 1.61 μM. Additionally, TH023 inhibits the activation of NF-κB and reduces the nuclear translocation of NF-κB p65. The compound demonstrates anti-inflammatory effects in a mouse model of LPS-induced acute sepsis and improves lung injury in mice.

YHS-12, a ionizable cationic lipid (pKa = 6.506), has been utilized both in vitro and in vivo for delivering siRNA and mRNA via lipid nanoparticles (LNPs). These LNPs comprise YHS-12 and a targeting peptide CRVLRSGSC aimed at macrophages, encapsulating chimeric antigen receptor mRNA targeted at methicillin-resistant Staphylococcus aureus (MRSA) and siRNA against caspase-11. The LNPs have enhanced the phagocytic efficiency against MRSA in RAW 264.7 macrophages and primary murine bone marrow-derived macrophages (BMDMs). Administered intravenously, these LNPs have reduced bacterial load in the bloodstream and increased survival rates in a sepsis model in cyclophosphamide-induced immunosuppressed mice.

Sulfazamet, a compound derived from sulfonamides, exhibits antibacterial activity against streptococcal sepsis.

Sulfazamet is a sulfonamide derivative exhibiting antibacterial activity against (Streptococci sepsis).

NF-κB/MAPK-IN-2 (compound 14) is a potent inhibitor of NF-κB and MAPK pathways. It effectively reduces the protein expression levels of p-p65, p-IκB, p-p38, p-JNK, and p-ERK. This compound decreases the release of TNF-α and IL-6 induced by LPS and inhibits the nuclear translocation of p65 and c-Fos. NF-κB/MAPK-IN-2 shows potential for research in sepsis.