A substance that augments, stimulates, activates, potentiates, or modulates the immune response at either the cellular or humoral level. A classical agent (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contains bacterial antigens. It could also be endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Its mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy is related to its antigen-specific immunoadjuvanticity.
| Member | Definition | Class |
|---|
| benphothiamine | A thioester that is a synthetic analogue of thiamine obtained by acylative cleavage of the thiazole ring and O-phospohorylation. | benfotiamine |
| krn 7000 | A glycophytoceramide having an alpha-D-galactosyl residue at the O-1 position and a hexacosanoyl group attached to the nitrogen. | 1-O-(alpha-D-galactosyl)-N-hexacosanoylphytosphingosine |
| levamisole | A 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole that has S configuration. It is used (generally as the monohydrochloride salt) to treat parasitic worm infections in pigs, sheep and cattle and was formerly used in humans as an adjuvant to chemotherapy for the treatment of various cancers. It is also widely used as an adulterant to coccaine. | levamisole |
| melatonin | A member of the class of acetamides that is acetamide in which one of the hydrogens attached to the nitrogen atom is replaced by a 2-(5-methoxy-1H-indol-3-yl)ethyl group. It is a hormone secreted by the pineal gland in humans. | melatonin |
| muramyl dipeptide | A glycopeptide that is N-propionyl-L-alanyl-D-alpha-glutamine in which the pro-R hydrogen of the propionyl group has been replaced by the oxygen at position 3 of 2-acetamido-2-deoxy-beta-D-glucopyranose. A peptidoglycan constituent of both Gram-positive and Gram-negative bacteria. | muramyl dipeptide |
| plerixafor | An azamacrocycle consisting of two cyclam rings connected by a 1,4-phenylenebis(methylene) linker. It is a CXCR4 chemokine receptor antagonist and a hematopoietic stem cell mobilizer. It is used in combination with grulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the perpheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. | plerixafor |
| plumbagin | A hydroxy-1,4-naphthoquinone that is 1,4-naphthoquinone in which the hydrogens at positions 2 and 5 are substituted by methyl and hydroxy groups, respectively. | plumbagin |
| pristane | A norterpene that is an acyclic saturated hydrocarbon derived from phytane by loss of its C-16 terminal methyl group. | pristane |
| squaric acid dibutyl ester | A cyclic ketone and diether that is a dibutyl ether derivative of squaric acid. | squaric acid dibutyl ester |
| swainsonine | An indolizidine alkaloid isolated from the plant Swainsona canescens with three hydroxy substituents at positions 1, 2 and 8. | swainsonine |
| tomatine | A steroid alkaloid that is tomatidine in which the hydroxy group at position 3 is linked to lycotetraose, a tetrasaccharide composed of two units of D-glucose, one unit of D-xylose, and one unit of D-galactose. | tomatine |
| Protein | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Drugs |
|---|
| 15-hydroxyprostaglandin dehydrogenase [NAD(+)] isoform 1 | Homo sapiens (human) | Potency | 26.6514 | 1 | 2 |
| 15-lipoxygenase, partial | Homo sapiens (human) | Potency | 3.1623 | 1 | 1 |
| 67.9K protein | Vaccinia virus | Potency | 0.7233 | 2 | 2 |
| aldehyde dehydrogenase 1 family, member A1 | Homo sapiens (human) | Potency | 31.8234 | 1 | 3 |
| AR protein | Homo sapiens (human) | Potency | 13.1187 | 6 | 7 |
| aryl hydrocarbon receptor | Homo sapiens (human) | Potency | 48.3550 | 2 | 4 |
| ATAD5 protein, partial | Homo sapiens (human) | Potency | 29.0810 | 1 | 1 |
| Ataxin-2 | Homo sapiens (human) | Potency | 1.3333 | 1 | 1 |
| ATP-dependent phosphofructokinase | Trypanosoma brucei brucei TREU927 | Potency | 8.4921 | 1 | 2 |
| ATPase family AAA domain-containing protein 5 | Homo sapiens (human) | Potency | 1.3333 | 1 | 1 |
| atrial natriuretic peptide receptor 1 precursor | Homo sapiens (human) | Potency | 3.0131 | 1 | 1 |
| Bloom syndrome protein isoform 1 | Homo sapiens (human) | Potency | 17.8592 | 2 | 4 |
| caspase 7, apoptosis-related cysteine protease | Homo sapiens (human) | Potency | 69.6372 | 1 | 1 |
| caspase-1 isoform alpha precursor | Homo sapiens (human) | Potency | 22.1060 | 1 | 2 |
| caspase-3 | Homo sapiens (human) | Potency | 69.6372 | 1 | 1 |
| Caspase-7 | Homo sapiens (human) | Potency | 19.9526 | 1 | 1 |
| Cellular tumor antigen p53 | Homo sapiens (human) | Potency | 6.1709 | 2 | 3 |
| cellular tumor antigen p53 isoform a | Homo sapiens (human) | Potency | 5.2712 | 2 | 4 |
| Chain A, 2-oxoglutarate Oxygenase | Homo sapiens (human) | Potency | 12.5364 | 1 | 3 |
| Chain A, ATP-DEPENDENT DNA HELICASE Q1 | Homo sapiens (human) | Potency | 22.3872 | 1 | 1 |
| Chain A, HADH2 protein | Homo sapiens (human) | Potency | 30.7369 | 1 | 3 |
| Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASE | Homo sapiens (human) | Potency | 28.1838 | 1 | 1 |
| Chain A, Putative fructose-1,6-bisphosphate aldolase | Giardia intestinalis | Potency | 0.1119 | 1 | 1 |
| Chain A, TYROSYL-DNA PHOSPHODIESTERASE | Homo sapiens (human) | Potency | 42.5559 | 1 | 3 |
| Chain B, HADH2 protein | Homo sapiens (human) | Potency | 30.7369 | 1 | 3 |
| chromobox protein homolog 1 | Homo sapiens (human) | Potency | 28.1838 | 1 | 1 |
| ClpP | Bacillus subtilis | Potency | 28.1838 | 1 | 1 |
| cytochrome P450 2D6 | Homo sapiens (human) | Potency | 30.1116 | 1 | 1 |
| cytochrome P450 2D6 isoform 1 | Homo sapiens (human) | Potency | 10.0000 | 1 | 1 |
| cytochrome P450 3A4 isoform 1 | Homo sapiens (human) | Potency | 25.7877 | 2 | 4 |
| cytochrome P450, family 19, subfamily A, polypeptide 1, isoform CRA_a | Homo sapiens (human) | Potency | 34.6614 | 1 | 3 |
| DNA polymerase kappa isoform 1 | Homo sapiens (human) | Potency | 10.0000 | 1 | 1 |
| dopamine D1 receptor | Homo sapiens (human) | Potency | 8.1995 | 1 | 1 |
| dual specificity mitogen-activated protein kinase kinase 1 | Homo sapiens (human) | Potency | 12.5893 | 1 | 1 |
| estrogen nuclear receptor alpha | Homo sapiens (human) | Potency | 16.5203 | 7 | 8 |
| euchromatic histone-lysine N-methyltransferase 2 | Homo sapiens (human) | Potency | 18.3398 | 1 | 2 |
| EWS/FLI fusion protein | Homo sapiens (human) | Potency | 2.6372 | 4 | 5 |
| flap endonuclease 1 | Homo sapiens (human) | Potency | 3.7686 | 1 | 1 |
| Fumarate hydratase | Homo sapiens (human) | Potency | 0.4176 | 1 | 1 |
| GABA theta subunit | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-1 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-2 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-3 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-4 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-5 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit alpha-6 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit beta-1 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit beta-2 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit beta-3 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit delta | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit epsilon | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit gamma-1 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit gamma-2 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit gamma-3 | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| Gamma-aminobutyric acid receptor subunit pi | Rattus norvegicus (Norway rat) | Potency | 25.7877 | 1 | 2 |
| geminin | Homo sapiens (human) | Potency | 0.5623 | 1 | 1 |
| GLI family zinc finger 3 | Homo sapiens (human) | Potency | 27.7231 | 1 | 1 |
| glucocorticoid receptor [Homo sapiens] | Homo sapiens (human) | Potency | 5.3680 | 3 | 3 |
| heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) | Homo sapiens (human) | Potency | 5.2276 | 1 | 2 |
| histone acetyltransferase KAT2A isoform 1 | Homo sapiens (human) | Potency | 39.8107 | 1 | 2 |
| Inositol monophosphatase 1 | Rattus norvegicus (Norway rat) | Potency | 13.5571 | 1 | 2 |
| Integrin alpha-IIb | Homo sapiens (human) | Potency | 5.1454 | 1 | 2 |
| Integrin beta-3 | Homo sapiens (human) | Potency | 5.1454 | 1 | 2 |
| interleukin 8 | Homo sapiens (human) | Potency | 74.9780 | 1 | 1 |
| lamin isoform A-delta10 | Homo sapiens (human) | Potency | 0.0008 | 1 | 1 |
| M-phase phosphoprotein 8 | Homo sapiens (human) | Potency | 0.1778 | 1 | 1 |
| Microtubule-associated protein tau | Homo sapiens (human) | Potency | 1.7169 | 2 | 4 |
| mitogen-activated protein kinase 1 | Homo sapiens (human) | Potency | 10.6639 | 3 | 4 |
| muscarinic acetylcholine receptor M1 | Rattus norvegicus (Norway rat) | Potency | 0.0631 | 1 | 1 |
| Nuclear receptor ROR-gamma | Homo sapiens (human) | Potency | 58.5706 | 1 | 2 |
| nuclear receptor ROR-gamma isoform 1 | Mus musculus (house mouse) | Potency | 8.7125 | 2 | 4 |
| nuclear receptor subfamily 1, group I, member 2 | Rattus norvegicus (Norway rat) | Potency | 3.1623 | 1 | 1 |
| nuclear receptor subfamily 1, group I, member 3 | Homo sapiens (human) | Potency | 41.4253 | 2 | 3 |
| peripheral myelin protein 22 isoform 1 | Homo sapiens (human) | Potency | 84.9214 | 1 | 1 |
| peroxisome proliferator activated receptor gamma | Homo sapiens (human) | Potency | 19.9721 | 2 | 2 |
| phosphopantetheinyl transferase | Bacillus subtilis | Potency | 37.6460 | 1 | 2 |
| polyprotein | Zika virus | Potency | 0.4176 | 1 | 1 |
| potassium voltage-gated channel subfamily H member 2 isoform d | Homo sapiens (human) | Potency | 15.8489 | 1 | 1 |
| pregnane X nuclear receptor | Homo sapiens (human) | Potency | 62.0642 | 1 | 1 |
| RAF proto-oncogene serine/threonine-protein kinase isoform b | Homo sapiens (human) | Potency | 25.1189 | 1 | 1 |
| RAR-related orphan receptor gamma | Mus musculus (house mouse) | Potency | 8.4127 | 1 | 1 |
| ras-related protein Rab-9A | Homo sapiens (human) | Potency | 14.1254 | 1 | 1 |
| regulator of G-protein signaling 4 | Homo sapiens (human) | Potency | 2.1192 | 1 | 1 |
| retinoic acid nuclear receptor alpha variant 1 | Homo sapiens (human) | Potency | 39.1599 | 1 | 1 |
| survival motor neuron protein isoform d | Homo sapiens (human) | Potency | 28.1838 | 1 | 1 |
| TDP1 protein | Homo sapiens (human) | Potency | 1.8668 | 2 | 6 |
| thioredoxin reductase | Rattus norvegicus (Norway rat) | Potency | 10.4824 | 2 | 4 |
| thyroid hormone receptor beta isoform 2 | Rattus norvegicus (Norway rat) | Potency | 2.3710 | 2 | 2 |
| Type-1A angiotensin II receptor | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1 | 1 |
| Type-1B angiotensin II receptor | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1 | 1 |
| Type-2 angiotensin II receptor | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1 | 1 |
| USP1 protein, partial | Homo sapiens (human) | Potency | 33.9508 | 1 | 2 |
| vitamin D3 receptor isoform VDRA | Homo sapiens (human) | Potency | 4.4173 | 1 | 2 |
| Protein | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Drugs |
|---|
| 10 kDa chaperonin | Escherichia coli | IC50 | 2.0450 | 2 | 2 |
| 10 kDa heat shock protein, mitochondrial | Homo sapiens (human) | IC50 | 6.3000 | 1 | 1 |
| 5'-nucleotidase | Rattus norvegicus (Norway rat) | IC50 | 20.2000 | 1 | 1 |
| 60 kDa chaperonin | Escherichia coli K-12 | IC50 | 250.0000 | 1 | 1 |
| 60 kDa chaperonin | Escherichia coli | IC50 | 2.0450 | 2 | 2 |
| 60 kDa heat shock protein, mitochondrial | Homo sapiens (human) | IC50 | 6.3000 | 1 | 1 |
| Acetylcholinesterase | Homo sapiens (human) | IC50 | 0.1000 | 1 | 2 |
| Acetylcholinesterase | Bos taurus (cattle) | IC50 | 0.1000 | 2 | 3 |
| Alkaline phosphatase, placental type | Homo sapiens (human) | IC50 | 400.0000 | 4 | 4 |
| Alkaline phosphatase, tissue-nonspecific isozyme | Homo sapiens (human) | IC50 | 16.1525 | 4 | 4 |
| Alkaline phosphatase, tissue-nonspecific isozyme | Homo sapiens (human) | Ki | 16.0000 | 1 | 1 |
| Alkaline phosphatase, tissue-nonspecific isozyme | Bos taurus (cattle) | IC50 | 19.4060 | 5 | 5 |
| Alkaline phosphatase, tissue-nonspecific isozyme | Bos taurus (cattle) | Ki | 1.8100 | 1 | 1 |
| Alpha-1,2-mannosidase | Bacteroides thetaiotaomicron VPI-5482 | Ki | 9.5000 | 2 | 6 |
| alpha-1,2-Mannosidase | Glycine max (soybean) | IC50 | 0.4000 | 1 | 1 |
| Alpha-1,2-mannosidase family protein | Bacteroides thetaiotaomicron VPI-5482 | Ki | 9.5000 | 2 | 4 |
| Alpha-1,2-mannosidase, putative | Bacteroides thetaiotaomicron VPI-5482 | Ki | 9.5000 | 2 | 6 |
| Alpha-1A adrenergic receptor | Rattus norvegicus (Norway rat) | IC50 | 0.0005 | 1 | 1 |
| Alpha-mannosidase 2 | Drosophila melanogaster (fruit fly) | Ki | 0.0030 | 1 | 1 |
| Alpha-mannosidase 2C1 | Rattus norvegicus (Norway rat) | IC50 | 1.7500 | 1 | 1 |
| Amine oxidase [flavin-containing] A | Homo sapiens (human) | IC50 | 3.0000 | 1 | 2 |
| Aromatase | Homo sapiens (human) | IC50 | 11.3000 | 1 | 1 |
| ATP-binding cassette sub-family C member 3 | Homo sapiens (human) | IC50 | 133.0000 | 1 | 2 |
| Bile salt export pump | Homo sapiens (human) | IC50 | 422.0000 | 2 | 3 |
| C-C chemokine receptor type 2 | Homo sapiens (human) | IC50 | 0.0001 | 2 | 2 |
| C-X-C chemokine receptor type 4 | Homo sapiens (human) | IC50 | 0.8234 | 37 | 37 |
| C-X-C chemokine receptor type 4 | Rattus norvegicus (Norway rat) | IC50 | 0.1080 | 1 | 1 |
| C-X-C chemokine receptor type 4 | Homo sapiens (human) | Ki | 6.1137 | 43 | 43 |
| Canalicular multispecific organic anion transporter 1 | Homo sapiens (human) | IC50 | 133.0000 | 1 | 2 |
| Carboxylic ester hydrolase | Equus caballus (horse) | IC50 | 0.1000 | 1 | 1 |
| Chain A, ALPHA-MANNOSIDASE II | Drosophila melanogaster (fruit fly) | IC50 | 0.0200 | 1 | 3 |
| Cholinesterase | Homo sapiens (human) | IC50 | 0.1000 | 1 | 2 |
| Cytochrome P450 1A1 | Homo sapiens (human) | IC50 | 2.7700 | 1 | 1 |
| Cytochrome P450 1A1 | Homo sapiens (human) | Ki | 30.7800 | 2 | 2 |
| Cytochrome P450 1A2 | Homo sapiens (human) | IC50 | 2.4600 | 1 | 1 |
| Cytochrome P450 1A2 | Homo sapiens (human) | Ki | 7.1800 | 2 | 2 |
| Cytochrome P450 1A2 | Rattus norvegicus (Norway rat) | Ki | 0.0003 | 1 | 1 |
| Cytochrome P450 1B1 | Homo sapiens (human) | IC50 | 6.1500 | 1 | 1 |
| Cytochrome P450 1B1 | Homo sapiens (human) | Ki | 14.0000 | 1 | 1 |
| Cytochrome P450 2C11 | Rattus norvegicus (Norway rat) | Ki | 0.0003 | 1 | 1 |
| Cytochrome P450 2C19 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| Cytochrome P450 2C9 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| Cytochrome P450 2D6 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| Cytochrome P450 2D6 | Homo sapiens (human) | Ki | 0.0003 | 1 | 1 |
| Cytochrome P450 3A4 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| Glycoside hydrolase family 92 | Bacteroides thetaiotaomicron VPI-5482 | Ki | 9.5000 | 2 | 4 |
| Histamine H3 receptor | Homo sapiens (human) | Ki | 0.0005 | 1 | 1 |
| Histone acetyltransferase KAT2B | Homo sapiens (human) | IC50 | 50.0000 | 3 | 3 |
| Histone acetyltransferase p300 | Homo sapiens (human) | IC50 | 15.5000 | 4 | 4 |
| Intestinal-type alkaline phosphatase | Bos taurus (cattle) | IC50 | 171.7220 | 5 | 5 |
| Intestinal-type alkaline phosphatase | Homo sapiens (human) | IC50 | 205.0420 | 5 | 5 |
| Lysosomal alpha-mannosidase | Homo sapiens (human) | IC50 | 6.6867 | 3 | 3 |
| M-phase inducer phosphatase 1 | Homo sapiens (human) | IC50 | 0.7000 | 1 | 1 |
| M-phase inducer phosphatase 2 | Homo sapiens (human) | IC50 | 3.1000 | 1 | 1 |
| Mannosyl-oligosaccharide alpha-1,2-mannosidase IA | Drosophila melanogaster (fruit fly) | IC50 | 0.0050 | 1 | 1 |
| Mannosyl-oligosaccharide alpha-1,2-mannosidase IA | Drosophila melanogaster (fruit fly) | Ki | 0.0030 | 1 | 1 |
| Melatonin receptor type 1A | Homo sapiens (human) | IC50 | 0.0025 | 18 | 18 |
| Melatonin receptor type 1A | Gallus gallus (chicken) | Ki | 0.0007 | 7 | 8 |
| Melatonin receptor type 1A | Homo sapiens (human) | Ki | 0.0003 | 67 | 69 |
| Melatonin receptor type 1B | Homo sapiens (human) | IC50 | 0.0035 | 12 | 12 |
| Melatonin receptor type 1B | Gallus gallus (chicken) | Ki | 0.0007 | 8 | 9 |
| Melatonin receptor type 1B | Homo sapiens (human) | Ki | 0.0004 | 62 | 64 |
| Melatonin receptor type 1C | Gallus gallus (chicken) | Ki | 0.0007 | 7 | 8 |
| Metabotropic glutamate receptor 1 | Rattus norvegicus (Norway rat) | IC50 | 0.0004 | 2 | 2 |
| Mitogen-activated protein kinase kinase kinase 14 | Homo sapiens (human) | IC50 | 100.0000 | 1 | 1 |
| Mu-type opioid receptor | Rattus norvegicus (Norway rat) | Ki | 0.0003 | 1 | 1 |
| Multidrug resistance-associated protein 4 | Homo sapiens (human) | IC50 | 133.0000 | 1 | 2 |
| Myeloperoxidase | Homo sapiens (human) | IC50 | 3.0000 | 1 | 1 |
| Nociceptin receptor | Mus musculus (house mouse) | Ki | 0.0003 | 1 | 1 |
| Palmitoleoyl-protein carboxylesterase NOTUM | Homo sapiens (human) | IC50 | 75.4000 | 1 | 1 |
| Phospholipase A-2-activating protein | Homo sapiens (human) | IC50 | 5.0000 | 1 | 1 |
| Putative alpha-1,2-mannosidase | Bacteroides thetaiotaomicron VPI-5482 | Ki | 9.5000 | 2 | 26 |
| Receptor tyrosine-protein kinase erbB-2 | Homo sapiens (human) | IC50 | 30.8000 | 1 | 1 |
| Replicase polyprotein 1ab | Severe acute respiratory syndrome coronavirus 2 | IC50 | 17.1000 | 1 | 1 |
| Replicase polyprotein 1ab | Severe acute respiratory syndrome-related coronavirus | IC50 | 17.1000 | 1 | 1 |
| Ribosyldihydronicotinamide dehydrogenase [quinone] | Homo sapiens (human) | IC50 | 7.3161 | 8 | 8 |
| Ribosyldihydronicotinamide dehydrogenase [quinone] | Homo sapiens (human) | Ki | 0.0422 | 2 | 2 |
| Thiosulfate sulfurtransferase | Homo sapiens (human) | IC50 | 0.0600 | 1 | 1 |
| Trypanothione reductase | Trypanosoma cruzi | IC50 | 28.0000 | 2 | 2 |