ligation

LP-935509 is highly brain-penetrant and reverses fully established pain behavior following the SNL procedure. LP-935509 is also an effective inhibitor of BIKE (IC50=14 nM) and a modest inhibitor of GAK (IC50=320 nM). LP-935509 is a selective, ATP-competit

Astragaloside IV (AS-IV), an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells. Astragaloside IV is a bioactive saponin first isolated from the dried plant roots of the genus Astragalus, which is used in traditional Chinese medicine.1 It dose-dependently inhibits human adenovirus type 3 (HAdV-3) in A549 cells (IC50 = 23 μM; LC50 = 865 μM).It inhibits replication of HAdV-3 and decreases HAdV-3-induced apoptosis. It has diverse protective effects for the cardiovascular, immune, digestive, and nervous systems. In particular, it reduces myocardial infarct size in dogs when administered prior to coronary ligation and reduces reperfusion arrhythmias in isolated rat hearts.

Dermorphin TFA is a new class of opioids-like peptides

The impact of spleen tyrosine kinase (Syk) signaling might be prominent in lupus because (i) Syk is a shared downstream signaling molecule among circulating immune complex, LPS, and (1→3)-β-D-glucan (BG), and (ii) all of these factors are detectable in the serum of Fc gamma receptor IIb-deficient (FcgRIIb-/-) mice with sepsis. Syk inhibition downregulated several inflammatory pathways in FcgRIIb-/- macrophages activated with BG + LPS suggesting the potential anti-inflammatory impact of Syk inhibitors in lupus. Indeed, administration of a Syk inhibitor prior to cecal ligation and puncture (CLP) sepsis in FcgRIIb-/- mice reduced baseline lupus-induced proinflammatory cytokines and attenuated sepsis severity as evaluated by mortality, organ injury, serum LPS, and post-sepsis serum cytokines.

Sivopixant (S-600918) (S-600918) is a potent and selective antagonist of P2X3 receptor (P2X3 IC 50 =4.2 nM; P2X2/3 IC 50 =1100 nM). Sivopixant shows strong analgesic effect .

AM 281, a cannabinoid antagonist, reduces neurologic dysfunction and mortality rate after cecal ligation and puncture in rats.

AC-099 (compound 3) serves as a selective full agonist at NPFF2R (EC50 = 1189 nM) and a partial agonist at NPFF1R (EC50 = 2370 nM). It has been shown to mitigate hypersensitivity induced by spinal nerve ligation in rats [1] [2].

Taurocholic acid 3-sulfate (TCA3S) is a metabolite of the conjugated bile acid taurocholic acid .1Plasma levels of TCA3S are elevated in wild-type andSortilin 1(Sort1) knockout mice at 6 hours following bile duct ligation (BDL) and are further elevated inSort1knockout mice at 24 hours post-BDL.2 1.Lefebvre, P., Cariou, B., Lien, F., et al.Role of bile acids and bile acid receptors in metabolic regulationPhysiol. Rev.89(1)147-191(2009) 2.Li, J., Woolbright, B.L., Zhao, W., et al.Sortilin 1 loss-of-function protects against cholestatic liver injury by attenuating hepatic bile acid accumulation in bile duct ligated miceToxicol. Sci.161(1)34-47(2018)

Etoposide phosphate disodium (BMY-40481 disodium), a phosphate ester prodrug of etoposide, functions as a potent chemotherapeutic agent by selectively inhibiting topoisomerase II, hindering the re-ligation of DNA strands. It is regarded as the active equivalent of etoposide, effectively inducing cell cycle arrest, apoptosis, and autophagy in cancer cells.

5’-O-DMT-Ri can be used in the synthesis of oligoribonucleotides[1]. [1]. Kadokura M. Synthesis of 4-thiouridine, 6-thioinosine, and 6-thioguanosine 3’,5’-O-bisphosphates as donor molecules for RNA ligation and their application to the synthesis of photoactivatable TMG-capped U1 snRNA fragments. J Org Chem. 2000 Aug 25;65(17):5104-13.

Dermorphin is agonist of μ-opioid receptor (MOR) agonist.

Z-LLY-FMK (Calpain Inhibitor IV) serves as an inhibitor of calpain, a family of proteases implicated in the apoptosis of various cell systems. Specifically, this compound suppresses intestinal cell apoptosis following common bile duct ligation [1].

δ14-Triamcinolone acetonide is a potential impurity found in commercial preparations of triamcinolone acetonide. Triamcinolone acetonide is a synthetic corticosteroid. It decreases cytokine levels, the firing rate of sensory neurons, and mechanical hypersensitivity in a rat spinal nerve ligation model when used at a dose of 1.5 mg/kg prior to and following surgery for three days. Triamcinolone acetonide also decreases outflow facility in a mouse model of steroid-induced glaucoma when 20 μl of a 40 mg/ml suspension is administered subconjunctivally. Formulations containing triamcinolone acetonide are used in the treatment of diabetic macular edema.

1. Tussilagone inhibits dendritic cell function through the induction of heme oxygenase-1. 2. Tussilagone has anti-cancer activity, might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer. 3. Tussilagone has anti

SIRT5 inhibitor 7 (compound 58), a selective and substrate-competitive SIRT5 inhibitor, exhibits anti-inflammatory properties by modulating protein succinylation and attenuating pro-inflammatory cytokine release. It demonstrates renal protective effects and is active in vivo, showing efficacy in AKI mouse models subjected to lipopolysaccharide (LPS) and cecal ligation/perforation (CLP)-induced sepsis-related acute kidney injury [1].

DBCO-PEG2-NHS ester is a click chemistry reagent featuring an azide group and an NHS ester, designed for copper-free Click Chemistry. It specifically and efficiently reacts with primary amines (e.g., lysine residue side chains or aminosilane-coated surfaces) under neutral or slightly basic conditions to form stable covalent bonds. The inclusion of a hydrophilic PEG spacer enhances water solubility and provides a flexible linkage, reducing steric hindrance during ligation. This compound, intended for research use only [1], is ideal for applications requiring precise and efficient bioconjugation.

BMS-986318 is a potent nonbile acid FXR agonist, displaying EC50 values of 53 nM and 350 nM in FXR Gal4 and SRC-1 recruitment assays, respectively. It exhibits a favorable ADME profile and shows effectiveness in mouse models of liver cholestasis and fibrosis caused by bile duct ligation. BMS-986318 is employed in research focusing on nonalcoholic steatohepatitis.

Pyrromecaine is a local anesthetic used for surface anesthesia. Pyromecaine has a wide spectrum of antiarrhythmic action, exerts a favorable effect on the contractility of the left ventricle, and on the myocardial blood flow following the ligation of the

T4 RNA ligase is an enzyme that facilitates the ligation of single-stranded DNA. It is utilized for the synthesis of enzymatic oligoribonucleotides and the 3′-terminal labeling of RNA [1] [2].

TC 14012, a peptidomimetic compound, acts as both an antagonist to the chemokine (C-X-C motif) receptor 4 (CXCR4; IC50 = 2.9 nM) and as an agonist for CXCR7, effectively recruiting β-arrestin in HEK293T cells that express CXCR7 (EC50 = 350 nM). Moreover, it demonstrates significant antiviral activity by reducing the cytopathic effects of HIV in MT-4 cells with an EC50 value of 0.4 nM and inhibiting HIV entry in vitro through a CXCR4-dependent pathway (IC50 = 19.3 nM). Additionally, TC 14012 suppresses chemokine (C-X-C motif) ligand 12 (CXCL12)-induced migration in MDA-MB-231 breast cancer and human umbilical vein endothelial cells (HUVECs) within the 10 to 1,000 nM concentration range. In a mouse model, administration of TC 14012 at 10 mg/kg significantly reduced infarct size following acute myocardial infarction induced by ligation of the left anterior descending (LAD) coronary artery.

11-Azidoundecanoic acid, a click chemistry reagent with an azide group, serves as a hydrophobic bioconjugation linker amenable to further modification via Staudinger ligation or Click chemistry. This compound is recognized as a substrate by lipoic acid ligase (LpIA) for labeling purposes [1] [2]. Additionally, 11-Azidoundecanoic acid can participate in copper-catalyzed azide-alkyne cycloaddition (CuAAc) with alkyne-bearing molecules and engage in strain-promoted alkyne-azide cycloaddition (SPAAC) with molecules featuring DBCO or BCN groups.

JHU-58 is a novel dipeptide MrgC agonist. JHU-58 inhibited both mechanical and heat hypersensitivity in rats after an L5 spinal nerve ligation (SNL). JHU58 attenuated the evoked excitatory postsynaptic currents in substantia gelatinosa (SG) neurons in wild-type mice, but not in Mrg knockout mice, after peripheral nerve injury.

UFP101 is a synthetic peptide that functions as an antagonist of the nociceptin receptor, demonstrating high affinity with a Ki of 0.06 nM in CHO cells expressing the human receptor. It exhibits selectivity for the nociceptin receptor over the κ-opioid receptor, with a Ki of 204 nM in CHO cells expressing the rat receptor. The compound effectively inhibits GTPγS release from the nociceptin receptor in CHO cell membranes, with an EC50 of 1.86 nM. When administered intracerebroventricularly at a dose of 10 nmol/animal, UFP101 prolongs the latency to tail withdrawal in the tail-flick test in mice, indicating its potential as an analgesic. Additionally, at doses of 0.003, 0.03, and 0.3 mg/kg, UFP101 enhances survival in a sepsis mouse model induced by cecal ligation and puncture, suggesting potential therapeutic applications in sepsis management.

LCC-12, a derivative of the biguanide metformin, acts as a copper (II) chelator. It efficiently forms a monomeric bond with copper (II) and at 20 µM, it mitigates hydrogen peroxide-induced oxidation from NADH to NAD+. At a concentration of 10 µM, LCC-12 significantly reduces the secretion of cytokines IL-1β, IL-2, IL-6, IL-8, and TNF-α, along with the downregulation of JAK2, STAT2, and IL-1 receptor-associated kinase 4 (IRAK4) in primary human cytokine-activated monocyte-derived macrophages (MDMs). Additionally, it decreases the presence of CD80+ and CD86+ within these macrophages at 10 µM. When administered at 0.3 mg/kg per day, LCC-12 enhances survival rates in mouse models exposed to sepsis, triggered either by lipopolysaccharide (LPS) or cecal ligation and puncture.

Kynurenic acid, an active metabolite of tryptophan, is synthesized through a kynurenine intermediate by kynurenine aminotransferases (KATs). It acts as an antagonist of both NMDA and AMPA receptors, as well as α7 nicotinic acetylcholine receptors (nAChRs; EC50s = 235, 101, and 7 µM, respectively), and functions as an agonist for the aryl hydrocarbon receptor (AhR) and G protein-coupled receptor 35 (GPR35; EC50s = 1.4 and 39 µM, respectively). In a neonatal rat model of cerebral hypoxic-ischemia, induced by carotid artery ligation, administration of kynurenic acid at 300 mg/kg prevents weight loss in the lesioned hemisphere. Additionally, at concentrations of 1 and 5 mg/ml, it protects against neurodegeneration in the rhabdomere of the eye in an Htt93QtransgenicDrosophila model of Huntington's disease. Elevated levels of kynurenic acid in the cerebrospinal fluid have been observed in patients with schizophrenia.

Ni(II) protoporphyrin IX is a metalloporphyrin compound characterized by its limited propensity for axial ligation and its distortion upon binding to ferrochelatase.

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.