(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].
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.
Coptisine is an alkaloid from Chinese goldthread, and acts as an efficient uncompetitive IDO inhibitor with a Ki value of 5.8 μM and an IC50 value of 6.3 μM.
Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy.IC50 Value: 17uM (GR reduced 5-HT-evoked contractions) [1]Target: 5-HT3 receptorin vitro: In rat forestomach GR reduced 5-HT-evoked contractions at IC50 17 /- 6 uM. In isolated rabbit heart, GR 0.003-0.03 nM dose-dependently reduced s-HT tachycardia; at high levels GR reduced submaximal and maximal responses to 5-HT [1].in vivo: Leukocyte accumulation was dose-dependently inhibited by granisetron both at 6 and 72 h after induction of inflammation. Granisetron increased PGE(2) level at a lower dose (50 microg/pouch) but higher doses (100 and 200 microg/pouch) inhibited the release. At the same time, TNFalpha production was decreased by the lower dose and increased by higher doses of granisetron in a reciprocal fashion [2]. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation [3].Clinical trial: Effect of External Heat on a Transdermal Granisetron Patch in Pharmacokinetics (PK) of Healthy Subjects. Phase 1
Gatifloxacin (hydrochloride) is an antibiotic of the fourth-generation fluoroquinolone family, it inhibits the bacterial enzymes DNA gyrase and topoisomerase IV.Target: AntibacterialGatifloxacin (hydrochloride) is the hydrochloride salt of Gatifloxacin which is an antibiotic of the fourth-generation fluoroquinolone family, that like other members of that family, inhibits the bacterial enzymes DNA gyrase and topoisomerase IV. Gatifloxacin had activity equal to that of tosufloxacin and activity more potent than those of norfloxacin, ofloxacin, ciprofloxacin, and sparfloxacin against the second-step mutants (grlA gyrA; gatifloxacin MIC range, 1.56 to 3.13 microg/ml) and had the most potent activity against the third-step mutants (grlA gyrA grlA; gatifloxacin MIC range, 1.56 to 6.25 microg/ml), suggesting that gatifloxacin possesses the most potent inhibitory activity against singly mutated topo IV and singly mutated DNA gyrase among the quinolones tested [1].Ophthalmic gatifloxacin 0.3% is at least as effective as ciprofloxacin at healing corneal ulcers infected with Pseudomonas aeruginosa when gatifloxacin is administered less frequently than ciprofloxacin. Trends favored gatifloxacin in fluorescein retention scores [2].Clinical indications: Bacterial infection FDA Approved Date: Toxicity: Hepatotoxicity; Acute pancreatitis [3]; Torsades de pointes [4]
L-Praziquanamine is a natural product.
Ampiroxicam(CP65703) is a nonselective cyclooxygenase inhibitor uesd as anti-inflammatory drug.Target: COXAmpiroxicam is a non-steroidal anti-inflammatory drug. It is a prodrug of piroxicam. Ampiroxicam inhibits the stretching response in mice induced by phenylbenzoquinone (PBQ) with maximum protective effect (MPE) of 2 mg/kg. Ampiroxicam inhibits swelling in a dose-responsive manner in the rat foot edema (RFE) assay with ED50 of 28 mg/kg at single oral dose and 7.8 mg/kg at 5 daily oral dose. Ampiroxicam blocks primary and secondary lesion development in rat adjuvant arthritis with ED50 of 2.2 mg/kg and 0.5 mg/kg, respectively. Ampiroxicam (3.2 mg/kg) leads to a plasma concentration of 12 μg/mL at a Tmax of 2 hours for piroxicam derived from ampiroxicam in rats [1]. Ultraviolet-A (UVA)-irradiated 1% Ampiroxicam sensitized in guinea pigs shows positive reaction in the patch testing to UVA-irradiated 1% Ampiroxicam and 1% thiosalicylate (TOS). Concentration of Ampiroxicam is easily reduced by the increase in UVA irradiation doses, as compared with that of piroxicam [2].