| Target Validation Information | |||||
|---|---|---|---|---|---|
| TTD ID | T40800 | ||||
| Target Name | Sodium pump subunit alpha-1 (ATP1A1) | ||||
| Type of Target |
Successful |
||||
| Drug Potency against Target | Acocantherin | Drug Info | IC50 = 3 nM | [5] | |
| Almitrine | Drug Info | IC50 = 220nM | [6] | ||
| Chloroprocaine | Drug Info | IC50 = 13000000 nM | [2] | ||
| DIGITOXIGENIN | Drug Info | IC50 = 500 nM | [1] | ||
| Action against Disease Model | Ciclopirox | Drug Info | C. albicans SC5314 was exposed to either medi uM alone or ciclopirox olamine at a concentration equivalent to the IC50 (0.24 mg/L) for 3 h. RNA was isolated and gene expression profiles were compared using DNA microarrays. Differential expression of select genes was confirmed by real-time reverse transcription (RT)-PCR. Mutants disrupted for CDR2 and both CDR1 and CDR2, as well as a clinical isolate overexpressing CDR1 and CDR2, were examined for changes in susceptibility to ciclopirox olamine.A total of 49 genes were found to be responsive to ciclopirox olamine, including 36 up-regulated genes and 13 down-regulated genes. These included genes involved in small molecule transport (HGT11, HXT5, ENA22, PHO84, CDR4), iron uptake (FRE30, FET34, FTR1, FTR2, SIT1) and cellstress (SOD1, SOD22, CDR1, DDR48). Mutants disrupted for CDR2 and both CDR1 and CDR2, as well as a clinical isolate overexpressing CDR1 and CDR2, showed no change in susceptibility to ciclopirox olamine compared with the respective parent. | [3] | |
| Deslanoside | Drug Info | Albino guinea pig erythrocytes (mainly alpha1-Na(+),K(+)-ATPase isoforms) enriched with Na(+),K(+)-ATPase isoforms were utilized to compare the inhibition promoted by brazilein with that of classical inhibitors such as the cardiac glycoside deslanoside. Analysis of inhibition curves revealed that unlike deslanoside, brazilein had a relatively low affinity for erythrocyte isoforms and failed to completely inhibit the Na(+),K(+)-ATPase activity. The extent of the maxim uM inhibition rate was about 50%. The inhibitory effect of brazilein was not antagonized by 10 mmol/l K(+), as observed with deslanoside. Electrocardiogram research in vivo showed that brazilein did not induce the ventricular arrhythmias observed with deslanoside, suggesting that brazilein might have a less adverse effect and higher therapeutic index than cardiac glycosides. | [4] | ||
| References | |||||
| REF 1 | 17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity r... J Med Chem. 2000 Jun 15;43(12):2332-49. | ||||
| REF 2 | Inhibition of the Na,K-ATPase of canine renal medulla by several local anesthetics. Pharmacol Res. 2001 Apr;43(4):399-403. | ||||
| REF 3 | Genome-wide expression profiling of the response to ciclopirox olamine in Candida albicans. J Antimicrob Chemother. 2005 May;55(5):655-62. | ||||
| REF 4 | Study on cardioactive effects of brazilein. Pharmacology. 2006;76(2):76-83. | ||||
| REF 5 | Involvement of (Na+ + K+)-ATPase in binding and actions of palytoxin on human erythrocytes. Biochim Biophys Acta. 1986 Sep 25;861(1):165-76. | ||||
| REF 6 | Effects of almitrine bismesylate on the ionic currents of chemoreceptor cells from the carotid body. Mol Pharmacol. 1998 Feb;53(2):330-9. | ||||
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