adjuvant-induced

Fendosal (HP-129) is a non-steroidal anti-inflammatory agent. It is 6.9 to 9.5 times more active than aspirin in the prophylactic and therapeutic adjuvant-induced polyarthritis models of chronic inflammation.

AP-18 is a potent and selective TRPA1 inhibitor. AP-18 inhibits activation of TRPA1 induced by 50 μM Cinnamaldehyde with an IC50 of 3.1 μM and 4.5 μM for human and mouse TRPA1, respectively. AP-18 could reverse complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia in mice. AP-18 could attenuate Yo-Pro uptake induced by 30 μM AITC in a concentration-dependent manner (IC50= 10.3 μM).

Trametinib (GSK1120212) is a MEK inhibitor that inhibits MEK1 and MEK2 (IC50=0.7/0.9 nM) with ATP non-competitive and oral activity. Trametinib activates autophagy and induces apoptosis.

1. Flavokawain B (Flavokavain B) has potent anti-inflammatory activity, can significantly inhibit production of NO and PGE2 in LPS-induced RAW 264.7 cells. 2. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathways. 3. Flavokawain B induces apoptosis, has the potential usefulness of FKB for prevention and treatment of hormone-refractory prostate cancer in an adjuvant setting. 4. Flavokawain B acts through ROS generation and GADD153 up-regulation to regulate the expression of Bcl-2 family members, thereby inducing mitochondrial dysfunction and apoptosis in HCT116 cells.

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)

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg/ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g/animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

Cryogenine is an alkaloid originally isolated from H. salicifolia that has anti-inflammatory activity.1 It inhibits prostaglandin synthetase (IC50 = 424 μM). Cryogenine (100 mg/kg per day, p.o.) reduces paw edema and the mean arthritic index in a rat model of adjuvant-induced polyarthritis.2 |1. Lema, W.J., Blankenship, J.W., and Malone, M.H. Prostaglandin synthetase inhibition by alkaloids of Heimia salicifolia. J. Ethnopharmacol. 15(2), 161-167 (1986).|2. Kosersky, D.S., Brown, J.K., and Malone, M.H. Effects of cryogenine on adjuvant-induced arthritis and serum turbidity in rats. J. Pharm. Sci. 62(12), 1965-1971 (1973).

I-287 is a selective, orally active PAR2 inhibitor that functions as a negative allosteric modulator of Gαq and Gα12/13 activity and their downstream effectors. It has been shown to attenuate Complete Freund's adjuvant-induced inflammation in mice, suggesting its utility in inflammation/immunology research [1].

K 41498 is a selective peptide antagonist targeting both corticotropin-releasing factor receptor 2α (CRF2α) and CRF2β, demonstrating high affinity with Kis of 0.66 and 0.62 nM, respectively, in HEK293 cells expressing these human receptors. Its selectivity is evident as it exhibits a significantly reduced affinity for CRF1 receptor (Ki = 425 nM in HEK293 cells expressing the human CRF1 receptor). Additionally, K 41498, when administered intravenously at 1.84 µg/animal, effectively mitigates urocortin-induced hypotension in rats. Furthermore, its intrathecal delivery ranging from 0.075 to 0.5 µmol/animal significantly lowers the mechanical paw withdrawal threshold in a rat model, indicating its potential utility in managing nociception triggered by complete Freund's adjuvant.

Baicalein monohydrate is an inhibitor of 12-lipoxygenase, leukotriene biosynthesis and release of lysosomal enzymes. It also inhibits cellular Ca2+ uptake and mobilization and adjuvant-induced arthritis.

Body Protection Compound 157 (BPC 157) is a pentadecapeptide derived from BPC, identified in gastric juice, exhibiting diverse biological activities. At 2 µg/ml, BPC 157 enhances primary rat tendon fibroblast cell migration and F-actin formation. Furthermore, doses of 0.01 and 10 µg/kg, intraperitoneally (i.p.), mitigate paw swelling, bone erosion, and mononuclear cell infiltration in the joints of rats with rheumatoid arthritis induced by complete Freund's adjuvant (CFA). It also diminishes gastric ulcer size in rats caused by indomethacin, aspirin, or diclofenac at these doses. Additionally, BPC 157 reduces catalepsy duration and tremor severity in a mouse model of Parkinson's disease triggered by MPTP.

JC-171, a selective inhibitor of the NLRP3 inflammasome, effectively inhibits LPS/ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages with an IC50 of 8.45 μM[1].

MF-592 is a potent and selective antagonists of the EP4 receptor. MF-592 demonstrated good functional potency (hEP4 IC50 = 3 nM) and potent inhibition of PGE2 modulated TNFa release in LPS stimulated human whole blood (hWB) (IC50 = 78nM). In addition, it showed an excellent oral pharmacokinetic (PK) profile and in vivo efficacy in a rat chronic adjuvant-induced-arthritis model (ED50 = 0.1 mg/kg/day).. MF-592 has a desirable overall preclinical profile that suggests it is suitable for further development.

Folinic acid (Leucovorin) is a biofolic acid that can be used in the treatment of methotrexate, often in combination with Methotrexate (MTX) to reduce MTX-induced toxicity, and can be used as an adjuvant treatment for colon cancer.

Taraxasterol acetate has anti-inflammatory activity in bino rats against carrageenan, formaldehyde and adjuvant induced inflammations. Taraxasterol acetate also displays potential antibacterial activities.

R-130823 is a ighly selective inhibition against mitogen-activated protein kinase p38alpha (IC50=22 nM). The release of tumor necrosis factor-alpha, interleukin-1beta, -6 and -8 was inhibited in lipopolysaccharide-stimulated human blood pretreated by R-130823 , with IC50 values of 0.089, 0.066, 0.95 and 0.16 microM, respectively. R-130823 reduced the established hind paw swelling in rat adjuvant-induced arthritis, while methotrexate showed no suppression. In the same model, R-130823 ameliorated adjuvant-induced hyperalgesia with rapid onset and long duration comparable to a cyclooxygenase-2 inhibitor, celecoxib.

Sodium D-mannuronate, derived from the seaweed Macrocystis pyrifera, shows promise as a therapeutic agent in studies of autoimmune encephalomyelitis (EAE), adjuvant-induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis [1].

Sodium thiosulfate (Pentahydrate) is an antioxidant and antifungal. Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use[3]. The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival[4]. Calciphylaxis is a potentially fatal disorder of abnormal calcium deposition. Treatment is multifaceted, and improved outcomes have been demonstrated with intravenous sodium thiosulfate; however, the use of this medication can be limited by its adverse effects[5]. TST (topical sodium thiosulfate) appears to be a relatively well-tolerated adjuvant treatment for CC(calcinosis cutis)[6]. The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effective and safe for the treatment of calciphylaxis, inducing complete remission[7].

Trametinib (DMSO solvate) (GSK-1120212 (DMSO solvate)) is a Highly Potent and Selective MEK Inhibitor that specifically inhibits MEK1/2(IC50 :2 nM)

AHR-10037 is a nonsteroidal anti-inflammatory drug with analgesic and antipyretic properties as well as a high therapeutic index and low gastric toxicity. AHR-10037 was comparable to indomethacin in suppressing acute (Evans blue-carrageenan pleural effusion) and chronic (adjuvant-induced arthritis) inflammation. Studies have shown that it is converted in vivo to a prodrug of cyclooxygenase inhibitors.