ADU-S100 ammonium salt (ML RR-S2 CDA ammonium salt) is an activator of stimulator of interferon genes (STING). ADU-S100 ammonium salt leads to potent and systemic tumor regression and immunity.

Paquinimod (ABR 25757) is a S100A9 inhibitor preventing S100A9 binding to TLR-4.

Imazamox ((±)-Imazamox) is a systemic herbicide with high selectivity, high activity, safety and broadspectrum activity. Imazamox inhibits the production of acetolactate synthase (ALS) in plants, which would then inhibit plant growth and ultimately lead to plant death.

4-Nonylphenol polyethoxylate (Nonoxinol-9) is a typical surfactant used as a vaginal spermicide. Spermicides are locally acting non-hormonal contraceptives. When present in the vagina during intercourse, they immobilize/inactivate/damage and/or kill sperms without eliciting systemic effects. 4-Nonylphenol polyethoxylate has been in use for more than 30 years as an over-the-counter (OTC) drug in creams, gels, foams and condom lubricants. It is the most commonly used spermicidal contraceptive in the UK and the USA. In several European countries, spermicides are no longer on the market.

Bisphenol A is an endogenous metabolic compound of phenols and is widely used in the production of epoxy resins and polycarbonate plastics. It is reproductive, developmental and systemic toxicant and is often classified as an endocrine disruptor. It has been linked to many diseases, including respiratory disease, cardiovascular disease, diabetes, kidney disease, obesity and reproductive disorders.

Osteogenic Growth Peptide, OGP acetate is a short, naturally occurring 14-mer growth factor peptide found in serum at μM concentrations. Osteogenic growth peptide OGP is a key factor in the mechanism of the systemic osteogenic response to local bone marro

Raxofelast (IRFI-016) is a hydrophilic, non-systemic, vitamin-like antioxidant that reduces ischemia-reperfusion injury in testis. Raxofelast is a good candidate compound for stopping oxidative stress after acute testicular torsion. Raxofelast has the potential to treat diabetic complications and atherosclerosis.

Methyl 2-(4-((3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propanoate is a selective herbicide, an inhibitor of fatty acid synthesis, and has a systemic effect. After the stem and leaves are treated, it is quickly absorbed by weeds and transmitted to the whole plant, hydrolyzed into acid, and inhibits the growth of root and stem meristems, resulting in death. For soybean, cotton, peanut, rape, nursery, flax, and other broad-leaved crops to control crabgrass, kangaroo, beef tendon grass, barnyard grass, foxtail, chinensis and other annual grass weeds and bermudagrass, imperatae, etc. ineffective against broadleaf grasses and sedges.

Bunazosin Hydrochloride (E 1015) is an alpha(1)-adrenoceptor antagonist used as a systemic antihypertensive and an ocular hypotensive drug.

Aminaftone, a derivative of 4-aminobenzoic acid, inhibits endothelin-1 (ET-1) production and can be used to study hypertension and systemic sclerosis.

Mefloquine (Ro 215998), a quinoline antimalarial agent, is an anti-SARS-CoV-2 entry inhibitor. Mefloquine is also a K+ channel (KvQT1/minK) antagonist with an IC50 of ~1 μM. Mefloquine can be used for malaria, systemic lupus erythematosus, and cancer research.

Bupirimate (Nimrod), an active ingredient in plant protection products, is commonly used as a systemic fungicide and finds applications in controlling powdery mildew in roses, apple plantations. It belongs to the family of pyrimidines.

An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.

Mesosulfuron-methyl (Mesosulfuronmethyl Mesosulfuron methyl) is a systemic herbicide. It is used for post-emergence control of grasses and other weeds in cereals.

TLR7/8/9 antagonist 2 is an orally active and highly bioavailable vTLR7/8/9 antagonist. TLR7/8/9 antagonist 2 inhibits HEK/hTLR7, HEK/hTLR8 and HEK/hTLR9 with IC50s of 0.011 μM, 0.029 μM and 0,052 μM, respectively. TLR7/8/9 antagonist 2 can be used to study auto-inflammatory diseases such as systemic lupus erythematosus or lupus nephritis.

Isoflupredone (Isoflupredonum) is a synthetic corticosteroid that acts in vivo by binding to glucocorticoid and corticosteroid receptors in animals (such as horses) to inhibit inflammatory cells and inhibit the expression of inflammatory mediators. Isoflupredone has anti-inflammatory and immunosuppressive effects and can be used to treat a variety of musculoskeletal, allergic and systemic inflammatory diseases.

DZ2002, an orally active, reversible, and low-cytotoxic type III SAHH inhibitor (Ki=17.9 nM), exhibits significant immunosuppressive activity. It effectively prevents experimental dermal fibrosis by reversing the profibrotic phenotype in multiple cell types, making it useful for studying autoimmune diseases like lupus syndrome and systemic sclerosis.

Nifedipine (Procardia) is a dihydropyridine calcium channel blocking agent. Nifedipine inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents.

Ensartinib (X-396) is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively. The ability of Ensartinib (X-396) to inhibit the growth of different cancer cell lines harboring ALK fusions or point mutations is tested. Ensartinib is potent in H3122 lung cancer cells harboring EML4-ALK E13;A20 (IC50: 15nM). Ensartinib is also potent in H2228 lung cancer cells harboring EML4-ALK E6a/b; A20 (IC50: 45 nM). Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC50: 9 nM). X-376 also inhibits SY5Y neuroblastoma cells harboring ALK F1174L, MKN-45 gastric carcinoma cells harboring MET dependent, HepG2 cells and PC-9 lung cancer cell lines harboring EGFR exon 19 del with IC50s of 68 nM, 156 nM, 9.644 μM and 2.989 μM, respectively[1]. The effects of Ensartinib (X-396) in vivo against H3122 xenografts are examined. A pharmacokinetic study reveals that Ensartinib shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with Ensartinib at 25mg/kg bid. Ensartinib significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, Ensartinib appears well-tolerated in vivo. Mouse weight is unaffected by Ensartinib treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of Ensartinib, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of Ensartinib at 20, 40, 80 mg/kg in SD rats, all animals survive to study termination. The no significant toxicity (NST) levels are determined to be 80mg/kg for Ensartinib. At NST levels, Ensartinib achieves an AUC of 66 μM×hr and a Cmax of 7.19 μM[1]. [1]. Lovly CM, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinaseinhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31.

Arg-Gly-Asp-Ser is an integrin-binding sequence that inhibits integrin receptor function. It decreases systemic inflammation via inhibition of collagen-triggered activation of leukocytes and attenuates expression of inflammatory cytokines, MMP-9, and iNOS

Metronidazole (Metronidazol) is a synthetic nitroimidazole derivative with antiprotozoal and antibacterial activities.

Taccalonolide AJ is a microtubule stabilizer; it has excellent and highly persistent antitumor efficacy when administered directly to the tumor, suggesting that the lack of antitumor efficacy seen with systemic administration of AJ is likely due to its sh

C12 Galactosylceramide is a bioactive sphingolipid. It inhibits IL-4 production by 53.84% in EL4 T cells when used at a concentration of 10 μM. C12 Galactosylceramide reduces the growth of human papillomavirus type 16-associated tumors in mice and reduces tumor recurrence following surgical removal or chemotherapy. It also reduces natural killer T cell activity, delays the onset of proteinuria, and improves survival in a mouse model of systemic lupus.

pBD-1 is an endogenous and constitutively expressed antimicrobial peptide (AMP) from porcine tissues, particularly expresses in pig mucosal epithelial sites with the contribution of mucosal and systemic host defenses in pigs.

Abetimus (LJP 394 free base), an immunosuppressant composed of four double-stranded DNA (dsDNA) oligonucleotides, can crosslink anti-dsDNA antibodies on B cell surfaces and reduce anti-dsDNA antibody levels, offering research potential for systemic lupus erythematosus [1].

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)

AWD-G256 is anti-arrhythmic substance.AWD-G256 had no significant effect on stroke volume, lung pressure, or systemic blood pressure.

Tricarbonyldichlororuthenium(II) dimer, a pharmacological CO donor, prevents ischemia/reperfusion (I/R)-induced oxidative damage to the gastric mucosa by enhancing gastric blood flow (GBF) and reducing DNA oxidation and systemic inflammatory response.

Nangibotide, a TREM-1 receptor inhibitor, modulates the innate immune response and has demonstrated the potential to reduce systemic and localized inflammatory reactions in rodent models of myocardial ischemia-reperfusion [1].

Auriculin A, a synthetic atrial natriuretic factor (ANF), exhibits hemodynamic properties by antagonizing renal vasoconstriction in dogs and affects arterial baroreflex regulation of heart rate, systemic blood pressure, and constant flow-perfused hind limb perfusion pressure in rabbits [1] [2].

Diclobutrazol is a potent systemic fungicide effective against rusts, powdery mildews, and other fungal phytopathogens. It exhibits high activity in controlling various crop diseases, making it a valuable pesticide option.

Flupyradifurone, a systemic nicotinic acetylcholine receptor (nAChR) agonist, disrupts signal transduction within the central nervous system of sucking pests, functioning as a butenolide insecticide [1].

BAY 41-8543 is a nitric oxide (NO)-independent stimulator of soluble guanylyl cyclase (sGC).

This LL-37 peptide is acetylated on the N-terminus and amidated on the C-terminus.It plays a key role in the first line of defense against local infection and systemic invasion of pathogens at sites of inflammation and wounds.

Frentizole, an immunosuppressive agent, is an inhibitor of the Aβ-ABAD interaction

TREM-1 inhibitory peptide M3 acts as a ligand-dependent antagonist of TREM-1, capable of suppressing systemic and pulmonary pro-inflammatory cytokine and chemokine production, thereby mitigating acute lung injury [1].

C5aR1 antagonist peptide, a biologically active linear peptide originating from the C-terminus of the chemokine complement fragment 5 anaphylatoxin (C5a), inhibits C5a binding and activity at human and rat C5a receptors. Overexpression of C5a is linked to various immunoinflammatory diseases, including arthritis, Alzheimer’s disease, cystic fibrosis, and systemic lupus erythematosus.

GSK1795091 (CRX-601) is a synthetic TLR4 agonist and immunologic stimulator with demonstrated antitumor activity. It serves as a vaccine adjuvant, enhancing both mucosal and systemic immunity to influenza virus vaccines.

Spesolimab (BI 655130) is an anti-interleukin-36 receptor antibody. IL-36 plays an important role in the immune system and is associated with a reduction in biomarkers associated with congenital Th1/Th17 and neutrophil pathways. Spesolimab can be used to study systemic pustular psoriasis, palmar and plantar impetigo (PPP), and atopic dermatitis.

ABT-281 is an ascomycin analog and a macrolactam T cell inhibitors with potent topical activity and reduced systemic exposure.

Iodoantipyrine (Arthripur) is a commonly-used indicator and is used to evaluate in rats by measuring torcular venous efflux after systemic injection of the indicator under conditions of normal and high CBF.

Triadimenol is a systemic fungicide with a broad spectrum. It inhibits the ergosterol - and gibberellin - biosynthesis, and thus the rate of cell division.

Osteogenic Growth Peptide, OGP is a short, naturally occurring 14-mer growth factor peptide found in serum at μM concentrations. Osteogenic growth peptide OGP is a key factor in the mechanism of the systemic osteogenic response to local bone marrow injury

Nangibotide TFA, a TREM-1 receptor inhibitor, modulates the innate immune response and attenuates both systemic and localized inflammatory reactions in rodent models of myocardial ischemia-reperfusion [1].

RIPK1-IN-16 is an orally active, potent RIPK1 inhibitor that mitigates excessive inflammation via inhibition of RIPK1-mediated necroptosis in vivo. It shields mice from TNF-induced systemic inflammatory response syndrome and sepsis [1].

IGF-I (24-41) is a 24-41 amino acid fragment of Insulin-like Growth Factor I (IGF-I). IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective

Anifrolumab（MEDI-546） is a potent type I interferon (IFN) receptor antagonist, a human monoclonal antibody that targets IFN.Anifrolumab inhibits the activity of type I interferon and is used for the prevention and treatment of systemic lupus erythematosus (SLE).

Prezalumab (AMG 557) is a human IgG2 monoclonal antibody against ICOSL and BAFF. Prezalumab can be used to study sjogren's syndrome cutaneous lupus erythematosus, psoriasis, systemic lupus erythematosus arthritis and systemic lupus erythematosus (SLE).

AMY-101 is a peptidic inhibitor of the central complement component C3 (KD: 0.5 nM). AMY-101 shows a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation.

Cytochrome P450 metabolites of arachidonic acid, such as 11(12)-EpETrE and 14(15)-EpETrE have been identified as endothelium derived hyperpolarizing factors with vasodilator activity. Soluble epoxide hydrolase (sEH) catalyzes the conversion of EpETrEs to the corresponding DiHETrEs thereby diminishing their activity. Inhibitors of sEH may therefore have clinical utility for treating hypertension and systemic inflammation. S-NEPC is a colorimetric substrate used to measure sEH activity. It also is a substrate for Glutathione S-transferase, microsomal epoxide hydrolase and porcine liver carboxylesterase. Hydrolysis of S-NEPC by sEH yields 4-nitrophenol which can be quantified spectrophotometrically at 405 nm. S-NEPC is adaptable for use in 96-well microwell plate readers.