cascade

Melagatran, a direct and orally active thrombin inhibitor, specifically inhibits thrombin without affecting other enzymes in the coagulation cascade or fibrinolytic enzymes. It does not rely on endogenous co-factors to exert its antithrombin effect, and may alleviate the harmful effects of endotoxemia. As a result, Melagatran offers a promising strategy for the prevention of arterial occlusion.

Diclofenac Potassium (CGP-45840B) is a nonsteroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in certain conditions.

Jasmonic acid (JA) is a phytohormone and plant growth regulator involved in plant defense and growth and development.Jasmonic acid plays an important role in signaling, inducing the MAP kinase cascade pathway and calcium channels.

L524-0366 ([1-(3-chlorophenyl)triazol-4-yl]-thiomorpholino-methanone) is a TWEAK-Fn14 signaling cascade inhibitor.

SF5 is an inhibitor of the apoptosis pathway. Which is through the JNK-p53-caspase apoptotic cascade.

Monensin is an antiprotozoal agent produced by Streptomyces cinnamonensis. It has an inhibitory effect on the Wnt/β-catenin signaling cascade. Monensin is a prospective anticancer drug for the therapy of neoplasia with deregulated Wnt signaling.

SKF-96365 hydrochloride (SKF96365) , a SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal Y cells. SKF-96365 hydrochloride can induce cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 hydrochloride treatment inhibited the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKIIγ or AKT abolished the effects of SKF-96365 on Y cells, suggesting a critical role of the CaMKIIγ/AKT signaling pathway in SFK-96365-induced biological effects. SKF-96365 hydrochloride inhibited hERG current in a concentration-dependent manner.

Desmethylanethol trithione (ADT-OH) is a derivative of anethole dithiolethione (ADT) and synthetic hydrogen sulfide (H2S) donor. In the in vitro glucose-oxygen deprivation (OGD) model, Desmethylanethol trithione markedly attenuated tPA-enhanced Akt activation and VEGF expression in brain microvascular endothelial cells. Finally, Desmethylanethol trithione improved functional outcomes in mice subjected to MCAO and tPA infusion. H2S donors reduced tPA-induced cerebral hemorrhage by possibly inhibiting the Akt-VEGF-MMP9 cascade. Administration of H2S donors has potential as a novel modality to improve the safety of tPA following the stroke.

WH-15 is a fluorogenic phospholipase C (PLC) reporter, exhibiting Michaelis-Menten constant (Km) values of 49, 30, and 86.1 µM for PLC-γ1, PLC-δ1, and PLC-β2, respectively. It undergoes enzymatic cleavage in a cascade reaction to produce fluorescent 6-aminoquinoline. This compound enables the imaging of PLC activity in live cells [1].

Endogenous peptide GPR83 agonist. ProSAAS-derived neuropeptide. Activates phospholipase C (PLC)-mediated signaling cascade in mouse hypothalamus.

Lappaol C has antioxidant and antiaging properties, it may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade. Lappaol C also has potential chemosensitizing activity, it may be candidates for developing novel adjuvant an

SAH-SOS1A TFA is a peptide-based SOS1/KRAS protein interaction inhibitor. SAH-SOS1A TFA binds to wild-type and mutant KRAS (G12D, G12V, G12C, G12S, and Q61H) with nanomolar affinity ( EC 50 =106-175 nM). SAH-SOS1A TFA directly and independently blocks nucleotide association. SAH-SOS1A TFA impairs KRAS-driven cancer cell viability and exerts its effects by on-mechanism blockade of the ERK-MAPK phosphosignaling cascade downstream of KRAS [1] .

Urokinase peptidolytic (Urokinase-type plasminogen activator) is a serine protease, an inactive form (zymogen) of the serine protease plasminogen. Activation of plasmin triggers a proteolytic cascade reaction, which in turn participates in thrombolysis or extracellular matrix degradation, implicated in vascular disease and cancer-related research [1] .

1. Lappaol F has antioxidant and antiaging properties, it may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade.
2. Lappaol F has potential chemosensitizing activity, it may be candidates for developing novel adju

Prothrombin (coagulation factor II) is produced in the liver and is post-translationally modified in a vitamin K-dependent reaction that converts ten glutamic acids on prothrombin into gamma-carboxyglutamic acid. Prothrombin is proteolytically cleaved to

PtdIns-(3,4,5)-P3 (PIP3) serves as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains such as phosphatidylinositol 3-kinase (PI3K) or PTEN. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking and initiates an intricate signaling cascade that has been implicated in cancer. 3,5-dimethyl PIT-1 is a dimethyl analog of PIT-1, the selective inhibitor of PIP3/Akt PH domain binding, that is designed for more favorable solubility in vivo. 3,5-dimethyl PIT-1 inhibits PI3K/Akt signaling (IC50 = 27 μM), suppressing PI3K-PDK1-Akt-dependent phosphorylation, which has been shown to reduce cell viability and induce apoptosis in PTEN-deficient U87MG glioblastoma cells (IC50 = 36 μM). 4T1 breast cancer growth is significantly attenuated in BALB/c mice with a dose of 1 mg/kg of 3,5-dimethyl PIT-1 per day.

CBR-470-1 is a potent inhibitor of glycolytic phosphoglycerate kinase 1 (PGK1) that activates NRF2 by increasing methylglyoxal levels. CBR-470-1 is a non-covalent Nrf2 activator with neuroprotective activity that protects SH-SY5Y neuronal cells from MPP+-induced cytotoxicity by activating the Keap1-Nrf2 cascade. cytotoxicity induced by MPP+.

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

Z-AEVD-FMK is an irreversible inhibitor of caspase-10 and related caspases.[1] At 10 µM, it can prevent the initiation of Fas signaling by caspase-10 in Jurkat T lymphoma cells, preventing Bid cleavage into its active form, caspase cascade activation, and apoptosis.[2]

EP6 is an inhibitor of 5-lipoxygenase (5-LO), which is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) which are involved in inflammatory diseases and allergic reactions.

Sanggenol L, a compound from the root bark of Morus alba, inhibits cell growth and promotes apoptotic cell death in melanoma skin cancer cells through activation of the cysteinyl asparaginase cascade and apoptosis-inducing factors. Sanggenol L has anticancer activity and antiproliferative effects and is used in the study of prostate cancer.

cGAMP (Cyclic GMP-AMPP) diammonium serves as an intrinsic second messenger in metazoans, initiating the production of interferons upon cytosolic DNA detection. It activates the stimulator of interferon genes (STING), subsequently triggering a signaling cascade that culminates in the synthesis of type I interferons and various immune mediators [1] [2] [3] [4].

Coronatine is a plant growth regulator synthesized by Pseudomonas syringae, mimicking bioactive jasmonic acid conjugates or octadecanoid signal molecules in higher plants, which induces pathogenic symptoms. It enhances the virulence of Pseudomonas syringae by triggering a signaling cascade that suppresses salicylic acid accumulation, thereby promoting infection [1] [2] [3] [4].

Cerevisterol is a cytotoxic steroid, can inhibit the activity of DNA polymerase alpha. It can stimulate NGF-mediated neurite outgrowth on PC12 cells.

Subasumstat (TAK-981) is a selective the SUMOylation enzymatic cascade inhibitor, has potential immune-activating and antineoplastic activities.

Pimecrolimus (SDZ-ASM 981), a calcineurin inhibitor immunosuppressant, binds to the receptor macrophilin-12 (FKBP-12) forming a complex that blocks the calcium-dependent signal transduction cascade mediated by calcineurin.

RO5068760 , a substituted hydantoin, is a potent, highly selective, non-adenosine triphosphate (ATP)-competitive MEK1/2 inhibitors. RO5068760 shows significant efficacy in a broad spectrum of tumors with aberrant mitogen-activated protein kinase pathway activation. In vitro, RO5068760 demonstrates MEK1 kinase inhibitory activity with an IC50 of 0.025 μM in a cRaf/MEK/ERK cascade assay RO5068760 showed superior efficacy in tumors harboring B-RafV600E mutation.

MAP855 is a potent, selective, orally active, ATP-competitive MEK1/2 kinase inhibitor with an IC50 value of 3 nM for MEK1 ERK2 cascade and a pERKEC50 value of 5 nM. MAP855 exhibits equal inhibition of wild-type and mutant MEK1/2.

The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(1,2-dioctanoyl) is a synthetic analog of natural phosphatidylinositol (PtdIns) containing C8:0 fatty acids at the sn-1 and sn-2 positions. The compound features the same inositol and diacyl glycerol (DAG) stereochemistry as that of the natural compound. The short fatty acid chains of this analog, compared to naturally-occurring PtdIns, gives it different physical properties including high solubility in aqueous media. PtdIns are phosphorylated to mono- (PtdIns-P; PIP), di- (PtdIns-P2; PIP2), and triphosphates (PtdIns-P3; PIP3). Hydrolysis of PtdIns-(4,5)-P2 by phosphoinositide (PI)-specific phospholipase C generates inositol triphosphate (IP3) and DAG which are key second messengers in an intricate biochemical signal transduction cascade.

Angstrom6 (A-6 peptide) is an 8 amino acid peptide derived from single chain urokinase fibrinogen activator (scuPA) that interferes with the uPA/uPAR cascade and abrogates the downstream effects.Angstrom6 has antitumor activity and inhibits tumor cell migration, invasion, and metastasis by binding to CD44 and modulating CD44-mediated cell signaling.

Alloferon 3 is a natural peptide that mediates signaling by the NF-kappa B pathway to enhance the recognition of viral and tumor antigens. It is known to induce the production of endogenic interferons that promote a cascade of defense responses and also e

Methylnissolin is a natural product isolated from Astragalus membranaceus that inhibits platelet-derived growth factor (PDGF)-BB-induced cell proliferation with an IC50 of 10 μM. It inhibits PDGF-BB-induced vascular smooth muscle cell proliferation by inhibiting the ERK1/2 MAP kinase cascade. It also inhibits PDGF-BB-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERIC1/2) mitogen-activated protein (MAP) kinases and has antibacterial and anticancer effects.

Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses[3]. In C3-/- mice alcohol-induced liver steatosis is absent or strongly reduced after chronic or acute alcohol exposure. This suggests that the complement system and its component C3 contribute to the development of alcohol-induced fatty liver and its consequences[4].AMY-101 TFA (Cp40 TFA) is a peptidic inhibitor of the central complement component C3 (KD: 0.5 nM). It shows a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation[5].a daily subcutaneous dose of AMY-101 (4 mg/kg bodyweight) was protective against NHP periodontitis, suggesting that patients treated for systemic disorders (e.g., paroxysmal nocturnal hemoglobinuria) can additionally benefit in terms of improved periodontal condition[6].Plasma concentrations of both C3 and Cp40 were measured periodically and complete saturation of plasma C3 was confirmed. No differences in hematological, biochemical, or immunological parameters were identified in the blood or tissues of animals treated with Cp40 when compared to those injected with vehicle alone. Further, skin wounds showed no signs of infection in those treated with Cp40.Cp40 treatment was associated with a trend toward accelerated wound healing when compared with the control group. In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3[7].

Diclofenac (Diclofenacum) is a nonsteroidal benzeneacetic acid derivative with anti-inflammatory activity. Diclofenac binds and chelates both isoforms of cyclooxygenase (COX-1 and-2), thereby blocking the conversion of arachidonic acid to pro-inflammatory-proprostaglandins.

Vasonatrin Peptide (VNP) TFA, a chimeric compound derived from atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP), exhibits venodilating properties reminiscent of CNP, natriuretic effects akin to ANP, as well as unique arterial vasodilating capabilities not characteristic of either parent peptide. Additionally, VNP TFA confers cardioprotection in diabetic ischemia-reperfusion injury by attenuating endoplasmic reticulum (ER) stress through the cGMP-PKG signaling cascade [1] [2] [3].

Cacospongionolide B is isolated from the sponge Fasciospongia cavernosa. The marine sponge natural product cacospongionolide B (1) is one of a class of compounds bearing a g-hydroxybutenolide which are known to inhibit multiple forms of secratory phospholipase A2,1 enzymes believed to initiate a cascade of biological events leading to inflammation.

SKI-178 is a sphingosine kinase 1 (SphK1) inhibitor with IC50 of 0.1-1.8 μM. It induces prolonged mitosis followed by apoptotic cell death through the intrinsic apoptotic cascade. The sustained activation of CDK1 during prolonged mitosis, mediated by SKI-178 leads to the simultaneous phosphorylation of the prosurvival Bcl-2 family members, Bcl-2 and Bcl-xl, as well as the phosphorylation and subsequent degradation of Mcl-1.

Tenacissoside H (Tenacissimoside C) has antitumor activity on esophageal cancer through arresting cell cycle and regulating PI3K/Akt-NF-κB transduction cascade.

1. Nardosinone has inhibitory effect on Ang II-induced hypertrophy in H9c2 cells, might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways. 2. Nardosinone could protect against the neuronal injury exposed to OGD, which may be relevant to the

The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(4)-P1 (1,2-dioctanoyl) is a synthetic analog of natural phosphatidylinositol (PtdIns) featuring C8:0 fatty acids at the sn-1 and sn-2 positions. The compound contains the same inositol and diacylglycerol (DAG) stereochemistry as the natural compound. PtdIns-(4)-P1 can be phosphorylated to di- (PtdIns-P2; PIP2) and triphosphates (PtdIns-P3; PIP3). Hydrolysis of PtdIns-(4,5)-P2 by phosphoinositide (PI)-specific phospholipase C generates inositol triphosphate (IP3) and DAG which are key second messengers in an intricate biochemical signal transduction cascade.

YO-2 is a selective plasmin inhibitor. YO-2 induces thymocyte apoptosis via activation of caspase cascade.

Lappaol A has antioxidant and antiaging properties, it may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade. Lappaol A also has potential chemosensitizing activity, it may be candidates for developing novel adjuvant an

Diclofenac sodium (GP 45840) is a non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.

Phospholipase A2 (PLA2) catalyzes the hydrolysis of phospholipids at the sn-2 position leading to the production of lysophospholipids and free fatty acids. Calcium-dependent cytosolic PLA2 (cPLA2α) is a 85 kDa enzyme that plays a key role in the arachidonic cascade and the inflammatory response associated with this metabolic pathway. CAY10502 is a potent inhibitor of calcium-dependent cytosolic PLA2α (cPLA2α) with an IC50 value of 4.3 nM for the purified enzyme from human platelets. It inhibits arachidonic acid mobilization from A23187-stimulated or TPA-stimulated human platelets with IC50 values of 570 and 0.9 nM, respectively.

Amyloid-β (1-42) (Aβ42) is a neurotoxic 42-amino acid protein fragment found in amyloid plaques in postmortem cerebral cortex from patients with Alzheimer's disease.1,2,3Aggregation of Aβ42 results in the formation of neurotoxic fibrils or globular oligomers.1Aβ42 accumulates in the brain of many transgenic mouse models of Alzheimer's disease and, in many models, the onset of amyloid deposition positively correlates with deficits in spatial learning and memory.4 1.Wolfe, M.S.Therapeutic strategies for Alzheimer's diseaseNat. Rev. Drug Discov.1(11)859-866(2002) 2.Iwatsubo, T., Odaka, A., Suzuki, N., et al.Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)Neuron13(1)45-53(1994) 3.Hardy, J.A., and Higgins, G.A.Alzheimer's disease: The amyloid cascade hypothesisScience256(5054)184-185(1992) 4.Jankowsky, J.L., and Zheng, H.Practical considerations for choosing a mouse model of Alzheimer's diseaseMol. Neurodegener.12(1)89(2017)

Pep19-2.5, a synthetic antitoxin peptide, inhibits the intracellular signaling cascade triggered by endotoxins by blocking the activity of lipopeptides (LP) and lipopolysaccharides (LPS) mediated through both transmembrane and cytosolic pattern recognition receptors (PRRs). This action disrupts the signaling pathways that normally result in inflammation and cell pyroptosis [1].

Mesalamine impurity P is an impurity of Mesalamine . 5-Aminosalicylic acid (Mesalamine) acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB[1]. [1]. Kyle Dammann, et al.PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation.Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2349-60.

Fascaplysin is a cyclin D kinase 4/ cyclin D1 inhibitor (IC50 = 0.35 μM). Fascaplysin induces caspase mediated crosstalk between autophagy and apoptosis through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells.

Antiproliferative agent-23, a microtubule-destabilizing agent (MDA), disrupts the tubulin-microtubule system, leading to apoptosis through a mitochondrion-dependent pathway. This involves downregulation of Bcl-2 protein, upregulation of Bax and Cyt c proteins, and activation of the caspase cascade. Additionally, it induces reactive oxygen species (ROS)-mediated endoplasmic reticulum stress in A549/CDDP cells (cisplatin-resistant cancer cell line) through the PERK/ATF4/CHOP signaling pathway, demonstrating anti-tumor activity [1].

Diclofenac Diethylamine, a non-selective COX inhibitor, is utilized as a nonsteroidal anti-inflammatory drug (NSAID).