4-Guanidinobutanoic acid is a normal metabolite present in low concentrations.
Tandospirone citrate is a potent and selective 5-HT1A receptor partial agonist (Ki = 27 nM) that displays selectivity over SR-2, SR-1C, α1, α2, D1 and D2 receptors (Ki values ranging from 1300-41000 nM). IC50 Value: 27±5 nM(Ki) [1]Target: 5-HT1Ain vitro: Tandospirone is most potent at the 5-HT1A receptor, displaying a Ki value of 27 +/- 5 nM. The agent is approximately two to three orders of magnitude less potent at 5-HT2, 5-HT1C, alpha 1-adrenergic, alpha 2-adrenergic, and dopamine D1 and D2 receptors (Ki values ranging from 1300 to 41000 nM). Tandospirone is essentially inactive at 5-HT1B receptors; 5-HT uptake sites; beta-adrenergic, muscarinic cholinergic, and benzodiazepine receptors [1]. 3H-SM-3997 bound rapidly, reversibly and in a saturable manner with high affinity to rat brain hippocampal membranes (Kd = 9.4 nM, Bmax = 213 fmol/mg protein) [2]. in vivo: Chronic treatment with tandospirone, at 0.2 and 1.0mg/kg/day, but not 2.0mg/kg/day, attenuated footshock stress-induced eLAC elevation in the mPFC [3]. Rats were acutely administered tandospirone (0, 0.1, and 1 mg/kg, i.p.). Tandospirone decreased the number of premature responses, an index of impulsive action, in a dose-dependent manner [4].Toxicity: It is not believed to be addictive but it is known to produce mild withdrawal effects (e.g. anorexia) after abrupt discontinuation.
Atropine sulfate is a competitive muscarinic acetylcholine receptor antagonist.IC50 value:Target: mAChRAtropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna), Jimson weed (Datura stramonium), mandrake (Mandragora officinarum) and other plants of the family Solanaceae. Atropine is a competitive antagonist of the muscarinic acetylcholine receptors (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system). Atropine dilates the pupils, increases heart rate, and reduces salivation and other secretions [1].
Gomisin G is an ethanolic extract of the stems of Kadsura interior; exhibits potent anti-HIV activity with EC50 and therapeutic index (TI) values of 0.006 microgram/mL and 300, respectively.
Lycopene is naturally occurring carotenoids found in tomato, tomato products, and in other red fruits and vegetables; exhibits antioxidant effects.
Erythromycin, an oral macrolide antibiotic produced by Streptomyces erythreus, reversibly binds to the 50S ribosome of bacteria, and inhibits protein synthesis.Target: AntibacterialErythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often prescribed for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including Mycoplasma and legionellosis. It was first marketed by Eli Lilly and Company, and it is today commonly known as EES (erythromycin ethylsuccinate, an ester prodrug that is commonly administered). It is also occasionally used as a prokinetic agent.Erythromycin estolate has been associated with reversible hepatotoxicity in pregnant women in the form of elevated serum glutamic-oxaloacetic transaminase and is not recommended during pregnancy. Some evidence suggests similar hepatotoxicity in other populations. Erythromycin displays bacteriostatic activity or inhibits growth of bacteria, especially at higher concentrations, but the mechanism is not fully understood. By binding to the 50s subunit of the bacterial 70s rRNA complex, protein synthesis and subsequent structure and function processes critical for life or replication are inhibited. Erythromycin interferes with aminoacyl translocation, preventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex. Without this translocation, the A site remains occupied and, thus, the addition of an incoming tRNA and its attached amino acid to the nascent polypeptide chain is inhibited. This interferes with the production of functionally useful proteins, which is the basis of this antimicrobial action.
ATP is a phosphate-group donor for substrate activation in metabolic reactions and the coenzyme for a large number of kinases.
Acevaltrate, isolated from Valeriana glechomifolia, inhibits the Na+/K+-ATPase activity in the rat kidney and brain hemispheres with IC50s of 22.8±1.1 μM and 42.3±1.0 μM, respectively[1].
Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase (NOS), and functions as a marker of endothelial dysfunction in a number of pathological states.
Propionylcarnitine is a propionyl ester of L-carnitine.
(S)-10-Hydroxycamptothecin is a clinical therapy agent against hepatoma.IC50 value:Target:In vitro: In vitro, the 10-hydroxycamptothecin nanosuspensions released the encapsulated drug with nearly zero-order kinetics, and the accumulative release reached 90% within 72 hours. In vitro cytotoxicity assay showed that the 10-hydroxycamptothecin nanosuspensions had significantly enhanced cytotoxicity against HepG2 cells compared to the commercially available 10-hydroxycamptothecin injections [1].In vivo: The in vivo study with H22 tumor-bearing mice and intravenous injection of the drug showed that in contrast to the 10-hydroxycamptothecin injections, the 10-hydroxycamptothecin nanosuspensions exhibited significantly enhanced biodistribution, particularly in the lung (393.40-fold AUC0–24 h, liver (192.35-fold AUC0–24 h, spleen (141.67-fold AUC0–24 h and tumor (64.21-fold AUC0–24 h. The 10-hydroxycamptothecin nanosuspensions also showed improved antitumor therapeutic efficacy over the injections (89.83% vs. 30.56%) [1].
Dihydrocoumarin is a compound found in Melilotus officinalis. Dihydrocoumarin is a yeast Sir2p inhibitor. Dihydrocoumarin also inhibits human SIRT1 and SIRT2 with IC50s of 208 μM and 295 μM, respectively[1].
Proctolin is an endogenous pentapeptide that acts as an excitatory neuromodulator.
Huperzine A, an active Lycopodium alkaloid extracted from traditional Chinese herb, is a potent, selective and reversible acetylcholinesterase (AChE) inhibitor and has been widely used in China for the treatment of Alzheimer's disease (AD). IC50 value:Target: AChEHuperzine A exhibited protective effects against d-gal-induced hepatotoxicity and inflamm-aging by inhibiting AChE activity and via the activation of the cholinergic anti-inflammatory pathway. The huperzine A mechanism might be involved in the inhibition of DAMPs-mediated NF-κB nuclear localization and activation. Huperzine A is a potential therapeutic agent for Alzheimer's disease.
Novobiocin Sodium is an antibiotic compound derived from Streptomyces niveus.Target: AntibacterialNovobiocin, also known as albamycin or cathomycin, is an aminocoumarin antibiotic that is produced by the actinomycete Streptomyces niveus, which has recently been identified as a subjective synonym for S. spheroides a member of the order Actinobacteria . Other aminocoumarin antibiotics include clorobiocin and coumermycin A1. The molecular basis of action of novobiocin, and other related drugs clorobiocin and coumermycin A1 has been examined. Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by targeting the GyrB subunit of the enzyme involved in energy transduction. Novobiocin as well as the other aminocoumarin antibiotics act as competitive inhibitors of the ATPase reaction catalysed by GyrB. The potency of novobiocin is considerably higher than that of the fluoroquinolones that also target DNA gyrase, but at a different site on the enzyme. The GyrA subunit is involved in the DNA nicking and ligation activity [1-4].
D(+)-Raffinose pentahydrate (D-Raffinose pentahydrate) is a trisaccharide composed of galactose, glucose, and fructose that occurs naturally in a variety of vegetables and grains. D(+)-Raffinose pentahydrate is a functional oligosaccharide.
Bergenin, a polyphenol, is a potent antinarcotic agent with antioxidant action. IC50 value: < 2.5 μM (antiplasmodial) [3]Target:In vitro: The naloxone-precipitated withdrawal symptom (jumping frequency) was significantly ameliorated (50% of control group) by administration of bergenin (20 mg/kg) in morphine-treated mice. Furthermore, morphine-induced down-regulation of glutathione (GSH) contents was reversed by bergenin administration in the frontal cortex and liver [2].In vivo: Bergenin attenuated inflammatory cell infiltration and decreased the concentration of NO, TNF-α, IL-1β, and IL-6, which were increased in LPS-induced mouse mastitis [1].
Cucurbitacin E is a natural compound which from the climbing stem of Cucumic melo L. Cucurbitacin E significantly suppresses the activity of the cyclin B1/CDC2 complex.
Caffeic acid is an inhibitor of both TRPV1 ion channel and 5-Lipoxygenase (5-LO).
Magnolol, a natural lignan isolated from the stem bark of Magnolia officinalis, is a dual agonist of both RXRα and PPARγ, with EC50 values of 10.4 µM and 17.7 µM, respectively.
Timosaponin AIII could inhibit acetylcholinesterase (AChE) activity, with an IC50 of 35.4 μM.
Tetradecanoylcarnitine is a human carnitine involved in β-oxidation of long-chain fatty acids.
Taxifolin exhibits important anti-tyrosinase activity. Taxifolin exhibits significant inhibitory activity against collagenase with an IC50 value of 193.3 μM.
3-Pyridineacetic acid is a higher homologue of nicotinic acid, a breakdown product of nicotine (and other tobacco alkaloids).
Timosaponin BII is an antioxidant and an anti-inflammatory agent.
Geldanamycin is a Hsp90 inhibitor with antimicrobial activity against many Gram-positive and some Gram-negative bacteria.
Loureirin B, a flavonoid extracted from Dracaena cochinchinensis, is an inhibitor of plasminogen activator inhibitor-1 (PAI-1), with an IC50 of 26.10 μM; Loureirin B also inhibits KATP, the phosphorylation of ERK and JNK, and has anti-diabetic activity.
Danshensu (sodium salt) is odium salt of danshensu from the widely used Chinese herb Danshen. It can inhibited phenylephrine- and CaCl2-induced vasoconstriction in Ca2+-free medium.In vitro: Sodium danshensu showed a biphasic effects on vessel tension. While low dosage of sodium danshensu produced small contraction possibly through transient enhancement of Ca2+ influx, high dosage produced significant vasodilation mainly through promoting the opening of non-selective K+ channels and small-conductance calcium-sensitive K+ channels in the vascular smooth muscle cells.[1]In vivo: Danshensu did not change the expression of AGEs but partly blocked the increased expression of RAGE in the hippocampus of diabetic mice. Danshensu could ameliorate the cognitive decline in streptozotocin-induced diabetic mice by attenuating advanced glycation end product-mediated neuroinflammation.[2]
Gentiopicroside, a naturally occurring iridoid glycoside, inhibits P450 activity, with an IC50 and a Ki of 61 µM and 22.8 µM for CYP2A6; Gentiopicroside has antianti-inflammatoryand antioxidative effects.
Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class.Target: SNRIVenlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder (MDD), as a treatment for generalized anxiety disorder, and comorbid indications in certain anxiety disorders with depression. In 2007, venlafaxine was the sixth most commonly prescribed antidepressant on the U.S. retail market, with 17.2 million prescriptions.Venlafaxine is a bicyclic antidepressant, and usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitters in the synapse. The neurotransmitters affected are serotonin and norepinephrine. Additionally, in high doses it weakly inhibits the reuptake of dopamine, with recent evidence showing that the norepinephrine transporter also transports some dopamine as well, since dopamine is inactivated by norepinephrine reuptake in the frontal cortex. The frontal cortex largely lacks dopamine transporters; therefore, venlafaxine can increase dopamine neurotransmission in this part of the brain. Venlafaxine interacts with opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as the alpha2-adrenergic receptor, and was shown to increase pain threshold in mice. When mice were tested with a hotplate analgesia meter (to measure pain), both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following intraperitoneal injection. These findings suggest venlafaxine's seemingly superior efficacy in severe depression as narcotics become increasingly used as a measure of last resort for refractory cases.