Andrology & Gynecology: Current Research
Transcription
Andrology & Gynecology: Current Research
Pehlivan M et al., Androl Gynecol: Curr Res 2015, 3:1 http://dx.doi.org/10.4172/2327-4360.1000135 Andrology & Gynecology: Current Research Research Article A SCITECHNOL JOURNAL Discovery of a New Anti Androgen Compound Mustafa Pehlivan* School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL 10 9AB, UK *Corresponding author: Mustafa Pehlivan, School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL 10 9AB, UK, Tel: 447758414188; E-mail: [email protected] Rec date:Nov 17, 2014Acc date: Mar 13, 2015Pub date: Mar 20, 2015 certain randomly generated compound is very unlikely to happen with the tool used, and such factors are actually what make drug discovery process difficult. Using Swiss, one can specifically select the option to target human DNA and then generate and enter a compound to the program to see what effects it will have on certain enzymes and how it may or may not inhibit what receptors. And this was exactly what was done for this compound as well. While there was a huge effort to see a high efficacy rate for inhibiting the most important receptor(s) specifically related to a certain disease, only the mentioned compound was successful in that process. The program automatically generates the related proteins which the compound may act on and shows the effectiveness on them. Results and Critical Discussion Abstract The purpose of this paper is to introduce a newly discovered anti androgen compound (pentabromo-dicyclohexane) which has a very high potential of being used as a medicine to treat prostate cancer and reduce the symptoms of cancer. The molecule has been discovered based on the Target predictor tool, Swiss, which is an online software used for drug discovery trials. It is evidenced in this paper why this compound will work better than any other drugs available to treat cancer based on statistical and enzymatic target binding activities. The results obtained by entering this compound into the software to obtain its effects on enzymatic receptors were the followings together with its Chemical structure [2]: Keywords: Drug; Discovery; Development; Pharmacokinetics; Pharmacodynamics; Pharmacology; ADME; Pharmacy Mechanism of Action of Anti-androgens Androgen receptor inhibitors reduce or eliminate symptoms of prostate cancer by inhibiting Androgen receptors [1]. The main advantage of this new compound is that it does not block any other receptors except androgen, and therefore it is very specific. Also another advantage of it in terms of its mechanism of inhibition is that its inhibition efficacy is about 90%, and therefore it would be a very efficient anti-cancer drug for prostate cancer and related diseases. Also when compared to other anti-Androgen drugs, this drug has a different and better enzalutamide activity. Materials and Methods While searching for a potential compound that may be used in the treatment of cancer in one of the trials, there has been a very high statistical efficacy rate (about 90%) that they tried molecule actually specifically binds only to androgen receptors and inhibit them. Such a compound would be effective and safe to patients since it is very specific in its target selectivity. The fact that computer generated efficacy statistics have shown that the efficacy for this molecule to specifically inhibit androgen receptors is about 90% predicts very high activity rate. Furthermore, production of this drug compound will not cost a lot by drug companies due to its organic structure. Obtaining a very high efficacy rate for specific inhibition of the target enzyme for a Model Figure 1: Predicted Activity of new androgen receptor inhibitor compound As obvious above, the efficacy for this drug molecule to inhibit androgen receptors is very high, and it is also obvious that it does that specifically. What is very special about this molecule is that its rings are both single bonded (cyclohexanes) (Figure 1). This drug molecule may also help reduce insulin resistance and female hair growth since such factors are related to the activity of androgen receptors Table 1. ADMET Predicted Profile Classification Result Probability Absorption All articles published in Andrology & Gynecology: Current Research are the property of SciTechnol, and is protected by copyright laws. Copyright © 2014, SciTechnol, All Rights Reserved. Citation: Pehlivan M (2015) Discovery of a New Anti Androgen Compound. Androl Gynecol: Curr Res 3:1. doi:http://dx.doi.org/10.4172/2327-4360.1000135 Blood-Brain Barrier BBB+ 0.9874 Human IntestinalAbsorption HIA+ 0.9948 Caco-2 Permeability Caco2+ 0.6947 P-glycoproteinSubstrate Non-substrate 0.6996 Non-inhibitor 0.8297 P-glycoproteinInhibitor Non-inhibitor 0.8442 RenalOrganicCationTransporter Non-inhibitor 0.822 CYP450 2C9 Substrate Non-substrate 0.8651 CYP450 2D6 Substrate Non-substrate 0.7925 CYP450 3A4 Substrate Non-substrate 0.635 CYP450 1A2 Inhibitor Inhibitor 0.603 CYP450 2C9 Inhibitor Inhibitor 0.5421 CYP450 2D6 Inhibitor Non-inhibitor 0.9459 CYP450 2C19 Inhibitor Non-inhibitor 0.5622 CYP450 3A4 Inhibitor Inhibitor 0.5 CYP InhibitoryPromiscuity High CYP InhibitoryPromiscuity 0.5766 Weakinhibitor 0.9553 Human Ether-a-go-go-Related Gene Inhibition Non-inhibitor 0.7945 AMES Toxicity Non AMES toxic 0.9098 Carcinogens Non-carcinogens 0.7247 FishToxicity High FHMT 0.97 TetrahymenaPyriformisToxicity High TPT 0.9983 HoneyBeeToxicity High HBT 0.8158 Biodegradation Not readybiodegradable 1 Acute Oral Toxicity IV 0.473 Carcinogenicity (Three-class) Non-required 0.5421 Value Unit Aqueoussolubility -5.6641 LogS Caco-2 Permeability 1.7727 LogPapp, cm/s Distribution Metabolism Excretion Toxicity ADMET Predicted Profile --- Regression Model Absorption Distribution Volume 3 • Issue 1 • 1000135 • Page 2 of 3 • Citation: Pehlivan M (2015) Discovery of a New Anti Androgen Compound. Androl Gynecol: Curr Res 3:1. doi:http://dx.doi.org/10.4172/2327-4360.1000135 Metabolism Excretion Toxicity RatAcuteToxicity 2.2752 LD50, mol/kg FishToxicity 0.2992 pLC50, mg/L TetrahymenaPyriformisToxicity 1.2481 pIGC50, ug/L Table 1: Predicted ADME of new compound (Pentabromodicyclohexane) that would be effective in prostate cancer models using ADME predictoronline Conclusion The permeability of the blood brain barrier for this drug is high as the results showed BBB+, where probability for this was shown to be close to 1 (close to 100%) [3]. Intestinal absorption for this drug in humans is also very high (close to 100%). Based on the results obtained, it will be worth synthesizing this compound both financially and therapeutically, as there is a huge market for cancer. Also it will not cost too much for its production, which is an advantage. Another advantage is that the drug compound is Hydrophobic like most other drugs which mean it will penetrate the Phospholipid bilayer of target cells easily. But most importantly, it will have a high efficacy and lower Volume 3 • Issue 1 • 1000135 side effects to patients while compared to other anti-androgen drugs based on its organic structure. References: 1. http://dermnetnz.org/treatments/antiandrogens.html 2. Gfeller D, Michielin O, Zoete V, Shaping the interaction of landscape of Bioactive molecules-Bioinformatics (2013) 29: 3073-3079 3. http://lmmd.ecust.edu.cn:8000/ • Page 3 of 3 •