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 •