Isotretinoin(13-cis-Retinoic acid) is a medication used for the treatment of severe acne. It was first developed to be used as a chemotherapy medication for the treatment of brain cancer, pancreatic cancer and more.Target: RAR/RXRIsotretinoin has been the most effective and long-lasting drug for the treatment of severe acne for more than 30 years and can achieve long-term remission in 70-80% of patients after a single course. The new evidence-based European S3-guideline recommends the use of Isotretinoin as a first-line medication for the treatment of severe papulopustular or conglobate acne, especially when prognostically unfavorable factors are present: family history of acne, early onset, marked seborrhea, localization on the trunk, scarring, psychosocial disability or persistent/late-type acne [1]. Five patients with pityriasis rubra pilaris were treated with isotretinoin from September 1982 through 1985. Isotretinoin at an average dose of 1.16 mg/kg/day for 16 to 24 weeks caused complete or almost complete clearing in four of the five patients [2]. isotretinoin produces significant anti-inflammatory effects by inhibition of monocyte and neutrophil chemotaxis across intact biologic barriers in vivo [3]. Isotretinoin 5 mg/day is effective in reducing the number of acne lesions, and improving patients dermatologic quality of life, with minimal adverse effects [4]. Clinical indications: Acne Toxicity: Isotretinoin is teratogenic. It also causes mucocutaneous side effects suck as cheilitis, dry skin, and dry eyes.
Arbutin(β-Arbutin) is a glycoside; a glycosylated hydroquinone extracted from the bearberry plant in the genus Arctostaphylos; inhibits tyrosinase and thus prevents the formation of melanin.IC50 value:Target: tyrosinase
Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, and was also selected as a Notch-1 inhibitor.IC50 value:Target: Notch-1In vitro: Tangeretin enhanced the radiosensitivity of GC cells as demonstrated by MTT and colony formation assays. Tangeretin also attenuated radiation-induced EMT, invasion and migration in GC cells, accompanied by a decrease in Notch-1, Jagged1/2, Hey-1 and Hes-1 expressions. Tangeretin triggered the upregulation of miR-410, a tumor-suppressive microRNA. Furthermore, re-expression of miR-410 prevented radiation-induced EMT and cell invasion [1]. In vivo: In this study, we investigated the in vivo anti-RSV activity of tangeretin in 3-week-old male BALB/c mice. A plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ-PCR) showed that tangeretin inhibited RSV replication in the lung of mice [2].
Alisol A 24-acetate is a natural product.
Hosenkoside K is a baccharane glycoside isolated from the seeds of impatiens balsamina.
Chlorogenic acid is a major phenolic compound in coffee and tea. It plays several important and therapeutic roles such as antioxidant activity, antibacterial, hepatoprotective, cardioprotective, anti-inflammatory, antipyretic, neuroprotective, anti-obesity, antiviral, anti-microbial, anti-hypertension.
Sarsasapogenin is a sapogenin from the Chinese medical herb Anemarrhena asphodeloides Bunge, with antidiabetic, anti-oxidative, anticancer and anti-inflamatory activities.
Cetirizine, a second-generation antihistamine, is a major metabolite of hydroxyzine, and a racemic selective H1 receptor inverse agonist used in the treatment of allergies, hay fever, angioedema, and urticaria. IC50 value:Target: Histamine H1 receptorCetirizine crosses the blood-brain barrier only slightly, reducing the sedative side-effect common with older antihistamines. It has also been shown to inhibit eosinophil chemotaxis and LTB4 release. At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis. The levorotary enantiomer of cetirizine, known as levocetirizine, is the more active form. From Wikipedia.
Salinomycin is an anticoccidial drug with potent anti-bacterial activity and an novel anticancer agent targeting human cancer stem cells.
Genistein, a soy isoflavone, is a multiple tyrosine kinases inhibitor which acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis.
Malotilate is a liver protein metabolism improved compound, which selectively inhibit the 5-lipoxygenase. IC50 Value:Target: 5-lipoxygenasein vitro: In an in vitro invasion assay using rat lung endothelial (RLE) cells, invasion of tumor cells which had been treated with MT (10 ng/ml, 24 h) was not affected; however, when RLE cells had been treated with MT, invasion was significantly inhibited in three cell lines (SAS, Ca9-22 and HSC-4) and a tendency to inhibition was also observed in other cell lines [1].in vivo: The improvement rates for choline esterase activity were significantly greater in the malotilate group than in the control group. Serum albumin levels significantly increased in the malotilate group but not in the control group [2]. In the rats treated with MT for 19 days after i.v. inoculation of c-SST-2 cells, lung metastasis was also significantly suppressed [3]. Malotilate prevented increases in serum markers of type III and IV collagen synthesis as well as accumulation of the collagens, laminin and fibronectin in the liver [4].Toxicity: Malotilate cytotoxicity to PBMCs, assessed by trypan blue dye exclusion and lactate dehydrogenase (LDH) release into the culture media, was found to be markedly increased by the addition of the NADPH generating system, indicating that metabolites play a significant role in toxicity [5].
(±) Anabasine is a biphasic muscle relaxant.
Streptozocin is a potent DNA-methylating agent, with IC50s of 11.7, 904 and 1024 μg/mL in HL60, K562 and C1498 cells respectively.
L-Citrulline is an amino acid derived from ornithine in the catabolism of proline or glutamine and glutamate, or from l-arginine via arginine-citrulline pathway.
Gigantol is a bibenzyl compound derived from several medicinal orchids. Giganto shows promising therapeutic potential against cancer cells. Gigantol is a novel inhibitor of the Wnt/β-catenin pathway.
Corydaline is an acetylcholinesterase inhibitor isolated from Corydalis yanhusuo.
Hippuric Acid, an acyl glycine produced by the conjugation of benzoic acid and glycine, is a normal component in urine as a metabolite of aromatic compounds from food.
TFAP is a selective cyclooxygenase-1 (COX-1) inhibitor, with an IC50 of 0.8 μM.
Sulfathiazole is an organosulfur compound that has been used as a short-acting sulfa drug.Target: AntibacterialSulfathiazole (20 μg/L) starts to be degraded between day 31 and day 38 in one of the two batch reactors containing different wastewater matrices. Sulfathiazole is degraded at a substantially faster rate than sulfamethoxazole or sulfamethazine in the nitrification process (S3) [1]. Recovery from spiked manure slurry samples is 64% for Sulfathiazole at pH 9. Sulfathiazole has acidity constant of pKa of 7.1and retention times (tR) of 7.8. S/N values for Sulfathiazole are above 100 at the 1 mg/kg level [2]. Sulfathiazole sorption to inorganic sorbents exhibits pronounced pH dependence consistent with sorbate speciation and sorbent charge properties. Sulfathiazole cations are most important for sorption to clay minerals, followed by neutral species [3].
Liquiritigenin, a flavanone isolated from Glycyrrhiza uralensis, is a highly selective estrogen receptor β (ERβ) agonist with an EC50 of 36.5 nM for activation of the ERE tk-Luc.
Bufalin a major digoxin-like immunoreactive component of the Chinese medicine Chan Su; has been shown to exert a potential for anticancer activity against various human cancer cell lines in vitro.IC50 value:Target: Anticaner natural compoundin vitro: bufalin remarkably inhibited growth in human gallbladder cancer cells by decreasing cell proliferation, inducing cell cycle arrest and apoptosis in a dose-dependent manner. Bufalin also disrupted the mitochondrial membrane potential (ΔΨm) and regulated the expression of cell cycle and apoptosis regulatory molecules. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that bufalin may be inducing mitochondria apoptosis pathways [1]. bufalin suppressed the protein levels associated with DNA damage and repair, such as a DNA dependent serine/threonine protein kinase (DNA-PK), DNA repair proteins breast cancer 1, early onset (BRCA1), 14-3-3 σ (an important checkpoint keeper of DDR), mediator of DNA damage checkpoint 1 (MDC1), O6-ethylguanine-DNA methyltransferase (MGMT) and p53 (tumor suppressor protein) [2]. TNF-α significantly increased p65 translocation into nucleus (P < 0.01) and enhanced NF-κB DNA-binding activity, which were dose-dependently inhibited by bufalin. Furthermore, bufalin attenuated the TNF-α-induced interleukin-1beta (IL-1β), IL-6, and IL-8 production in RAFLSs in a concentration-dependent manner [3]. bufalin enhanced TRAIL-induced apoptosis in MCF-7 and MDA-MB-231 breast cancer cells by activating the extrinsic apoptotic pathway. Bufalin also promoted the clustering of death receptor 4 (DR4) and DR5 in aggregated lipid rafts [4].in vivo: bufalin (0.3 and 0.6 mg/kg, i.p.) potently decreased carrageenan-induced paw edema. Bufalin down regulated the expression levels of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) during these treatments [5].
Pseudouridine, the most abundant modified nucleoside in non-coding RNAs, enhances the function of transfer RNA and ribosomal RNA by stabilizing RNA structure.
Fumaric acid, associated with fumarase deficiency, is identified as an oncometabolite or an endogenous, cancer causing metabolite.
Pirmenol hydrochloride inhibits IK.ACh by blocking muscarinic receptors. The IC50 of Pirmenol for inhibition of Carbachol-induced IK.ACh is 0.1 μM.
Vinflunine is a new vinca alkaloid uniquely fluorinated with the properties of mitotic-arresting and tubulin-interacting activity.Target: Microtubule/TubulinThe major effects of Vinflunine on dynamic instability are a slowing of the microtubule growth rate, an increase in growth duration, and a reduction in shortening duration. The effects of Vinflunine on the readmilling rate is examined by following [3H]GTP incorporation into MAP-rich microtubules, and the IC50 is 0.42 μM [1]. Vinflunine induced mitotic accumulation with IC50 with 18.8 nM, which decreases the centromere dynamicity by 44% and increases the time centromeres spent ina paused state by 63% [2]. Treatment of Vinflunine induces a rapid change in endothelial cell shape: cells retracts and assumes a rounded morphology. Mean IC50 values are 9.9 × 10-5 M × 10-5 M for fibronectin and 5.0× 10-5 M × 10-5 M for type IV collagen. A short 4 hours exposure of endothelial cells to Vinflunine at 10-8 0.05). An ID50 value (dose which inhibits 50% of bFGF-induced neovascularisation) is calculated as 1 mg/kg. Low doses of Vinflunine reduce the number of experimental liver metastases by human LS174T colon cancer cell. A slight overall decrease in liver metastatic foci is already observed at the very low dose of 0.16 mg/kg Vinflunine, although maximal overall inhibition is reached at the maximal tolerated dose (MTD) of 20 mg/kg [3].
Brefeldin A is a specific inhibitor of protein trafficking which blocks the protein transport from the endoplasmic reticulum to the Golgi complex.
(-)-Epigallocatechin is the most abundant flavonoid in green tea, can bind to unfolded native polypeptides and prevent conversion to amyloid fibrils.IC50 value:Target: in vitro: EGCG is a potent inhibitor of amyloidogenic cystatin I66Q amyloid fibril formation in vitro. Computational analysis suggests that EGCG prevents amyloidogenic cystatin fibril formation by stabilizing the molecule in its native-like state as opposed to redirecting aggregation to disordered, amorphous aggregates [1]. Combined curcumin and EGCG treatment reduced the cancer stem-like Cluster of differentiation 44 (CD44)-positive cell population. Western blot and immunoprecipitation analyses revealed that curcumin and EGCG specifically inhibited STAT3 phosphorylation and STAT3-NFkB interaction was retained [2]. EGCG exhibited a MIC and MBC of 5μg/mL and 20μg/mL respectively and effectively eradicated E. faecalis biofilms. EGCG induced the formation of hydroxyl radicals in E. faecalis. The addition of DIP protected E. faecalis against EGCG-mediated antibacterial effects. At sub-MIC, EGCG induced significant down-regulation of E. faecalis virulence genes [3].
Naringin is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. Naringin exhibits biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities.
Enalapril is an angiotensin converting enzyme (ACE) inhibitorTarget: ACEEnalapril belongs to a class of medications called angiotensin converting enzyme inhibitors. Normally angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II constricts blood vessels, increasing blood pressure. By inhibiting ACE, Enalapril decreases levels of angiotensin II leading to less vasoconstriction and decreased blood pressure.