pathogenesis

Iptacopan hydrochloride (LNP023 hydrochloride) is an orally bioavailable, highly potent and highly selective factor B inhibitor with an IC50 of 10 nM. Iptacopan hydrochloride shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM.

Patamostat mesylate (E-3123) is a potent protease inhibitor with IC50 values of 39 nM for trypsin, 950 nM for plasmin, and 1.9 μM for thrombin. This compound demonstrates promising potential in suppressing the pathogenesis and development of acute pancreatitis.

J-147 is an experimental drug with reported effects against both Alzheimer's disease and ageing in mouse models of accelerated aging. It is a curcumin derivative and a potent neurogenic and neuroprotective drug candidate initially developed for the treatment of neurodegenerative conditions associated with aging that impacts many pathways implicated in the pathogenesis of diabetic neuropathy.

Patamostat (E-3123) is a potent protease inhibitor that effectively inhibits trypsin, plasmin, and thrombin with IC50 values of 39 nM, 950 nM, and 1.9 µM, respectively. Research suggests it might suppress the pathogenesis and development of acute pancreatitis [1] [2].

β-Amyloid (1-42), human, is a 42-amino acid peptide integral to the pathogenesis of Alzheimer disease.

Uric acid sodium, scavengers of oxygen radicals, is a potent and common antioxidant that helps maintain stable blood pressure and resist oxidative stress. Uric acid sodium, which removes reactive oxygen species (ROS) such as singlet oxygen and peroxynitrite, has an inhibitory effect on lipid peroxidation and is associated with the pathogenesis of gout joint disease and the formation of calcium oxalate stones.

Biotin-β-Amyloid (1-42), human TFA, also known as Biotin-Amyloid β-Peptide (1-42) (human) TFA, is a biotin-labeled 42-amino acid peptide implicated in the pathogenesis of Alzheimer's disease.

Amyloid precursor c-terminal peptide has the amino acid sequence Gly-Tyr-Glu-Asn-Pro-Thr-Tyr-Lys-Phe-Phe-Glu-Gln-Met-Gln-Asn. APP is best known as the precursor molecule whose proteolysis generates beta-amyloid (Aβ), a 37 to 49 amino acid peptide whose am

Epsilon-(gamma-glutamyl)-lysine is an N(6)-acyl-L-lysine derivative that forms bonds between extracellular matrix (ECM) components with the assistance of the enzyme tissue transglutaminase (tTg). These bonds are implicated in the pathogenesis of diseases such as non-diabetic kidney disorders and glaucoma filtration.

Amyloid β Peptide (42-1)(human) acetate is the inactive form of Amyloid β Peptide (1-42). Amyloid β Peptide (42-1)(human) acetate is a 42-amino acid peptide which plays a key role in the pathogenesis of Alzheimer disease.

Quorum sensing is a regulatory system used by bacteria for controlling gene expression in response to increasing cell density. This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production. Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). Regulation of bacterial quorum sensing signaling systems to inhibit pathogenesis represents a new approach to antimicrobial therapy in the treatment of infectious diseases. AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group), and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family. C15-HSL is a product of Y. pseudituberculosis.

Quorum sensing is a regulatory process used by bacteria for controlling gene expression in response to increasing cell density. This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production. Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group) and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family. C14:1-δ9-cis-(L)-HSL is a long-chain AHL that functions as a signaling molecule in the quorum sensing of A. vitis. Regulating bacterial quorum sensing signaling can be used to inhibit pathogenesis and thus, represents a new approach to antimicrobial therpy in the treatment of infectious diseases.

ZHSI-1 is an EV71 (Enterovirus 71) inhibitor that blocks EV71 CVA16 replication and virus-induced pyroptosis linked to viral pathogenesis. It effectively prevents EV71 infection in neonatal and young mice in animal models and can be used to study viral infections such as hand, foot, and mouth disease (HFMD) [1].

GIP, rat TFA (glucose-dependent insulinotropic polypeptide), a 42-amino acid peptide secreted by K cells in the duodenum and jejunum, promotes insulin release from pancreatic beta cells, supports beta cell proliferation, and enhances their survival. This rat-origin bioactive peptide, along with GLP (gastric-like peptide), belongs to the intestinal insulinotropic hormone family and is implicated in lipid homeostasis and potentially in the pathogenesis of obesity. Recent research suggests GIP's multifaceted role in these metabolic processes.

Neuraminidase-IN-5 (Compound 5b), a dihydrofurocoumarin derivative, acts as a potent neuraminidase (NA) inhibitor, exhibiting significant inhibition with an IC 50 of 0.02 μM. Given NA's role in influenza pathogenesis, this compound emerges as a promising candidate for anti-influenza drug development [1].

eIF4A3-IN-17, a silvestrol analogue, disrupts the assembly of the eIF4F translation complex, exhibiting EC50 values of 0.9, 15, and 1.8 nM for myc-LUC, tub-LUC, and growth inhibition of MBA-MB-231 cells, respectively. This compound holds potential for research in human cancer pathogenesis [1].

GS-621763, a prodrug of GS-441524, exhibits antiviral activity against SARS-CoV-2 pathogenesis.

Grisnilimab (WT1), an IgG2a monoclonal antibody targeting CD7, acts as a tumor suppressor in the pathogenesis of Wilms' tumor. It modulates the transcription of various genes and may be involved in post-transcriptional RNA processing [1].

Insulin-degrading enzyme (IDE) is a thiol-sensitive zinc-metallopeptidase that acts as the major insulin-degrading protease in vivo, mediating the termination of insulin signaling. [1] In addition to regulating insulin action in diabetes pathogenesis, IDE plays a role in Varicella-Zoster virus infection and degradation of amyloid-β, a peptide implicated in Alzheimer's disease. ML-345 is a small molecule inhibitor that selectively targets cysteine819 in IDE with an EC50 value of 188 nM. [2] It demonstrates 10-fold selectivity for IDE over a panel of enzymes with reactive cysteine residues.[2] Reference:[1]. Maianti, J.P., McFedries, A., Foda, Z.H., et al. Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones. Nature 511(7507), 94-98 (2014).[2]. Bannister, T.D., Wang, H., Abdul-Hay, S.O., et al. ML345, a small-molecule inhibitor of the insulin-degrading enzyme (IDE). 1 R03 DA024888-01 (MLSCN cycle 6), 1-41 (2014).

Quorum sensing is a regulatory process used by bacteria for controlling gene expression in response to increasing cell density. This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production. Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group) and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family. C18:1-δ9 cis-(L)-HSL is a long-chain AHL that may have antimicrobial activity and thus, might be used to inhibit pathogenesis by regulating bacerial quorum sensing signaling.

TNF-α-IN-2 is a highly potent and orally bioavailable inhibitor of tumor necrosis factor alpha (TNFα), exhibiting an IC50 of 25 nM in the HTRF assay. It induces conformational changes in the TNFα trimer upon binding, disrupting signaling when the trimer interacts with TNFR1. TNF-α-IN-2 holds promise as a valuable tool for investigating the pathogenesis of rheumatoid arthritis [1].

APOL1-IN-1 is a potent inhibitor of apolipoprotein L1 (APOL1) that can be used to study the pathogenesis of focal segmental glomerulosclerosis (FSGS) and nondiabetic kidney disease (NDKD), facilitating research into these diseases.

β-Amyloid(28-35) human is a neurotoxic β-amyloid peptide fragment that contributes to Alzheimer's disease pathogenesis by interacting with neuronal membranes, modulating its secondary structure and toxicity. It also exhibits anisotropic effects on the acidic phospholipid DPH, thereby increasing the internal fluidity within lipid membrane bilayers [1].

nAChR antagonist 1 (compound B15) is a highly effective antagonist of α7 nAChR, with an IC50 value of 3.3 μM, making it an ideal candidate for investigating the pathogenesis of schizophrenia, Alzheimer's disease, and inflammatory disorders [1].