Colistin adjuvant-1 is a mucin adjuvant with enhanced mucin-enhancing activity against gram-negative bacteria. colistin adjuvant-1 exhibits inhibition of NF-κB (IC50: 0.209 μM).

Colistin adjuvant-2 is a compound that acts as a potentiation agent for colistin, effectively enhancing its activity against Gram-negative bacteria [1].

Aluminum Hydroxide is an orally active main form of aluminum used as an adjuvant. Aluminum hydroxide-based adjuvant researches including the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway.

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.

RS09 2TFA (1449566-36-2 free base) is a TLR4 agonist. Promotes NF-κB nuclear translocation and induces inflammatory cytokine secretion in RAW264.7 macrophages in vitro. It acts as an adjuvant in vivo and enhances X-15 specific antibody serum concentrations.

Semustine, a DNA alkylating agent, is a cancer chemotherapy compound that is nephrotoxic in patients with malignant melanoma receiving adjuvant chemotherapy for the adjuvant treatment of leukemia.

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).

1. Cinnamaldehyde (Cinnamic Aldehyde) has antipyretic activity. 2. Cinnamaldehyde is a sedative agent. 3. Cinnamaldehyde inhibits invasive capabilities of MDA-MB-435S cells was correlated with down-regulating the expression of miR-27a. 4. Cinnamaldehyde induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects. 5. Cinnamaldehyde appears to be a promising candidate as an adjuvant in combination therapy with 5-fluorouracil (5-FU) and oxaliplatin (OXA), two chemotherapeutic agents used in CRC treatment. The possible mechanisms of its action may involve the regulation of drugmetabolizing genes. 6. Cinnamaldehyde plays a certain role in inhibiting the occurrence and progression of melanoma and its action mechanism may be manifested by inhibiting expression of VEGF and HIF-α, thus blood vessel simulation and formation of new blood vessels of melanoma cells, and growth of tumors accordingly.

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.

Polyinosinic-polycytidylic acid potassium (Poly(I:C) potassium), a synthetic double-stranded RNA analog, serves as an agonist for toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I)-like receptors (RIG-I and MDA5), offering applications in immunotherapy. Its sodium variant enhances both innate and adaptive immune responses when used as a vaccine adjuvant, and is instrumental in modifying the tumor microenvironment. Additionally, Poly(I:C) potassium can directly induce apoptosis in cancer cells [1] [2] [3].

RS 09 TFA, a TLR4 agonist, promotes NF-κB nuclear translocation and induces the secretion of inflammatory cytokines in RAW264.7 macrophages in vitro. Additionally, as an adjuvant in vivo, RS 09 TFA enhances serum concentrations of X-15 specific antibodies when co-administered with X-15-KLH in mice.

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)

α-Carotene is isolated from yellow-orange and dark-green vegetables. α-Carotene is used as an anti-metastatic agent or as an adjuvant for anti-cancer drugs.

QS-21, an immunostimulatory saponin, is a powerful vaccine adjuvant that stimulates both Th2 humoral and Th1 cell-mediated immune responses by interacting with antigen presenting cells (APCs) and T cells. Additionally, QS-21 activates the NLRP3 inflammasome, leading to the release of cytokines IL-1β and IL-18, which are dependent on caspase-1.

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

Poly(I:C):Kanamycin (1:1) sodium is a symmetric complex combining Poly(I:C) sodium, a synthetic double-stranded RNA analog acting as a TLR3 and RIG-I/MDA5 agonist, with Kanamycin, an antibacterial agent effective against both Gram-negative and positive bacteria by inhibiting translocation and causing miscoding on the 70S ribosomal subunit. Poly(I:C) sodium serves as a potent vaccine adjuvant, bolstering innate and adaptive immunity and prompting apoptosis in cancer cells [1] [2]. Meanwhile, Kanamycin exhibits significant efficacy against Mycobacterium tuberculosis, including drug-resistant strains, and Klebsiella pneumoniae, offering valuable insights for tuberculosis and pneumonia research [3] [4] [5] [6].

ODN 2395, a class C oligodeoxynucleotide and TLR9 agonist, serves as a vaccine adjuvant. Its sequence is 5'-tcgtcgttttcggcgc:gcgccg-3' [1].

ODN 1668 is a class B CpG oligodeoxynucleotide (ODN) and serves as a TLR-9 agonist. It acts as an immunostimulatory sequence, making it effective as a vaccine adjuvant. Its sequence is 5'-tccatgacgttcctgatgct-3’ [1] [2].

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)

Methyl elaidate (Elaidic Acid Methyl Ester) is a synthetic fatty acid methyl ester used as an adjuvant in the formulation of plant protection products.

alpha-Amyrin palmitate is antiarthritic in the adjuvant model of arthritis in rats. alpha-Amyrin palmitate is a potent non-competitive inhibitor of chymotrypsin (Ki=6 microM), it also shows weak cytotoxicity against the A2780 human ovarian cancer cell line.

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.

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).

cGAMP disodium is a cyclic dinucleotide (CDN) found in bacteria that acts as an endogenous second messenger affecting interferon production in response to cytoplasmic DNA. cGAMP disodium cascades signals from type I interferons and other immune mediators by activating interferon gene stimulator (STING). cGAMP disodium is a potent sublingual immune adjuvant that enables better immune function (serum anti-PA neutralization and airway secretions anti-PA SIgA response).

Cyclic diadenylate (c-di-AMP) sodium functions as a STING agonist by binding to the STING transmembrane protein, thus activating the TBK3-IRF3 signaling pathway. This activation prompts the production of type I IFN and TNF. Additionally, c-di-AMP sodium serves as a bacterial second messenger in Gram-positive bacteria, where it plays crucial roles in regulating cell growth, survival, and virulence, as well as the host immune response. It also acts as a potent mucosal adjuvant by stimulating both humoral and cellular responses [1] [2] [3] [4].

ODN 1018 (1018 ISS), an oligodeoxynucleotide and a TLR-9 agonist, serves as a synthetic immunostimulatory sequence and vaccine adjuvant. The sequence is 5′-TGACTGTGAACGTTCGAGATGA-3′ [1] [2].

ODN 2007, a class B CpG ODN (oligodeoxynucleotide) and Toll-like receptor (TLR) ligand, serves as an immunomodulator and vaccine adjuvant, promoting enhanced immune responses across mammals, fish, and humans. Its sequence is 5'-TCGTCGTTGTCGTTTTGTCGTT-3' [1] [2] [3].

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

Flunarizine is a non-selective calcium entry blocker and a histamine H1 receptor blocker. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of

Platycoside E (Platycodin E) is a platycodigenin-type saponin isolated from the root of Platycodon grandiflorum with haemolytic activity and adjuvant potential.

Germacrene D has antibacterial and antifungal activities and can be used as an adjuvant agent in the application of aminoglycosides and azoles. Germacrene D is isolated from Bursera species.

AXC-715 hydrochloride is a TLR7/TLR8 dual agonist, can be used for synthesis of antibody-adjuvant immunoconjugates, comprising an antibody construct that binds programmed death-ligand 1 (PD-L1) linked to one or more adjuvants.

Uproleselan sodium (GGI-1271) is a small molecule E-selector antagonist originally targeted at AML as an adjuvant to standard chemotherapy for hematological malignancies.

Platycoside A has hemolytic activity and adjuvant potential on the immune responses to Newcastle disease virus-based recombinant avian influenza vaccine. It induces the IgG and IgG1 antibody responses in the immunized mice.

PA3552-IN-1 is an antibiotic adjuvant that can reduce the expression of PA3552 and restore the sensitivity of MDR Pseudomonas aeruginosa DK2 strain to Polymyxin B.

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].

Cholicamideβ (compound 6), a self-assembling small molecule cancer vaccine adjuvant, forms low cytotoxicity virus-like particles and upon binding to peptide antigens, enhances dendritic cell-mediated antigen presentation and induces antigen-specific T-cell responses, with the ability to induce apoptosis and necrosis [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.

CoPoP, a liposome-based vaccine adjuvant, holds potential for application in cancer research [1].

Vitamin E succinate (D-alpha-Tocopherol Succinate) is an antioxidant tocopherol that belongs to the vitamin E class of compounds Vitamin E succinate has antitumor activity, induces apoptosis, and is used as an adjuvant in the treatment of cancer and in the synthesis of INVITE, a biocoupling compound.

TLR4 agonist. Promotes NF-κB nuclear translocation and induces inflammatory cytokine secretion in RAW264.7 macrophages in vitro. Acts as an adjuvant in vivo; enhances X-15 specific antibody serum concentrations, when administered with X-15-KLH in mice.

Levoleucovorin Calcium (CL307782), a calcium salt of the folinic acid, is used in cancer chemotherapy as an adjuvant.

Cyclic di-IMP (sodium salt) (c-di-IMP) is a synthetic second messenger structurally related to the bacterial second messengers cyclic di-GMP and cyclic di-AMP . C-di-IMP has adjuvant properties when co-administered with antigens in vitro and by mucosal routes in vivo. C-di-IMP enriches the population of MHC class I and II, CD80, CD86, CD40, and CD54 positive dendritic cells derived from murine bone marrow. It also stimulates macrophages at 500 ng/ml. Mice immunized with β-galactosidase (β-gal) plus c-di-IMP through the intranasal route show a humoral immune response, evidenced by an increase in IgG titers up to 2-fold compared to mice immunized with β-gal alone. Mice immunized with β-gal plus c-di-IMP also exhibit a Th1/Th2 response, indicating that the adjuvant activity of c-di-IMP leads to a cellular immune response as well.

IMD-biphenylA, a novel imidazoquinolinone-based dimer, functions as an NF-κB immunomodulator and enhances the adjuvant properties of small molecule immune potentiators.

Trehalose 6-behenate is a Th1/Th17 skewing vaccine adjuvant.

Gantacurium chloride is a benzylisoquinoline alkaloid, which may be used as an adjuvant in anesthesia.

BAY-1797 is an orally active and selective P2X4 antagonist (IC50: 211 nM against human P2X4) with anti-nociceptive and anti-inflammatory effects. BAY-1797 displays no or very weak activity on the other P2X ion channels.

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.