Papers by ABHISHEK THAKUR
Letters in Drug Design & Discovery, 2014
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Bioinformation, 2016
Indoleamine-2,3-dioxygenase (IDO) an immunoregulatory enzyme and emerging as a new therapeutic dr... more Indoleamine-2,3-dioxygenase (IDO) an immunoregulatory enzyme and emerging as a new therapeutic drug target for the treatment of cancer. Carboranes, an icosahedral arrangement of eleven boron atoms plus one carbon atom with unique pharmacological properties such low toxicity, isosterism with phenyl ring and stability to hydrolysis. On the other hand, carboranes are known to increase the interaction of ligand with non-polar region of the protein provides an excellent platform to explore these carboranes towards designing and development of novel, potent and target specific drug candidates with further enhanced binding affinities. Despite of their many potential applications, molecular modeling studies of carborane-substituted ligands with macromolecules have been rarely reported. Previously, we have demonstrated the promising high binding affinity of Withaferin-A (WA) for IDO. In this present study, we investigated the effect of carborane substitutions on WA compound towards developin...
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The discovery of promising targets for anticancer drug development has emerged with many potentia... more The discovery of promising targets for anticancer drug development has emerged with many potential enzymes. Among these, the aurora family of kinases has become a very lucrative target with some potential inhibitors in its
arsenal. Recent findings show that targeting aurora B itself is sufficient to exhibit anticancer activity. When compared
with other anticancer targets, aurora B has a very limited number of specific inhibitors. Recently GSK1070916 and reversine were discovered as promising new aurora B inhibitors. Amongst these GSK1070916 emerged as the most potent
molecule targeting aurora B. Taking the scaffold of GSK1070916 as a reference, new molecules were designed by isosteric/bioisosteric and fragment based modifications. Furthermore, an accurate cross-platform docking, MM/GBSA based
rescoring, molecular dynamics simulation were carried out to compare the binding conformation and affinities of the designed molecules with the references. Top two designed molecules showed better docking score and a better binding free
energy profile as compared to reversine and GSK1070916 with the best ligand retaining conserved hydrogen bond and
salt bridge interactions with Ala173, Ala233 and Lys122. The binding mode of top two designed ligands is relatively
similar to that of reversine and GSK1070916. Molecular dynamics simulations proved that the identified hits are rather
stable in the enzyme active site pocket, which further confirms the potential of the designed ligands as a specific target for
aurora B.
We believe that findings of this study will provide medicinal chemists with potential markers towards the design of potent
anticancer drug design targeting aurora B and a broad range of aurora kinases.
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Drafts by ABHISHEK THAKUR
In spite of tremendous advancement in the field of cancer therapy, it is still the leading cause ... more In spite of tremendous advancement in the field of cancer therapy, it is still the leading cause of death worldwide. One of the newer targets in the field of cancer therapeutics is 5'Adenosine Mono Phosphate activated protein kinase (AMPK). In vitro and in vivo evidences suggest anti-cancer activity of AMPK. AMPK activation may promote catabolism while preventing the anabolic processed of cell. Thus, it may modulate cellular protein and lipid metabolism thus affecting cell growth and division. Here we review the mechanisms of action of AMPK modulators as future anti-cancer agents.
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A predominant number of diseases affecting women are related to female hormones. In most of
the c... more A predominant number of diseases affecting women are related to female hormones. In most of
the cases, these diseases are reported to be associated with menstrual problems. These diseases
affect female reproductive organs like the breast, uterus and ovaries. Estrogen is the main
hormone responsible for the menstrual cycle, so irregular menstruation is primarily due to a
disturbance in estrogen levels. Estrogen imbalance leads to various pathological conditions in
pre-menopausal women, such as endometriosis, breast cancer, colorectal cancer, prostate cancer,
poly cysts, intrahepatic cholestasis of pregnancy, osteoporosis, cardiovascular diseases, obesity,
etc. In this review, we discuss common drug targets and therapeutic strategies for the treatment
of diseases caused by deficient estrogen levels by using acupuncture and compounds of natural
origin.
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Papers by ABHISHEK THAKUR
arsenal. Recent findings show that targeting aurora B itself is sufficient to exhibit anticancer activity. When compared
with other anticancer targets, aurora B has a very limited number of specific inhibitors. Recently GSK1070916 and reversine were discovered as promising new aurora B inhibitors. Amongst these GSK1070916 emerged as the most potent
molecule targeting aurora B. Taking the scaffold of GSK1070916 as a reference, new molecules were designed by isosteric/bioisosteric and fragment based modifications. Furthermore, an accurate cross-platform docking, MM/GBSA based
rescoring, molecular dynamics simulation were carried out to compare the binding conformation and affinities of the designed molecules with the references. Top two designed molecules showed better docking score and a better binding free
energy profile as compared to reversine and GSK1070916 with the best ligand retaining conserved hydrogen bond and
salt bridge interactions with Ala173, Ala233 and Lys122. The binding mode of top two designed ligands is relatively
similar to that of reversine and GSK1070916. Molecular dynamics simulations proved that the identified hits are rather
stable in the enzyme active site pocket, which further confirms the potential of the designed ligands as a specific target for
aurora B.
We believe that findings of this study will provide medicinal chemists with potential markers towards the design of potent
anticancer drug design targeting aurora B and a broad range of aurora kinases.
Drafts by ABHISHEK THAKUR
the cases, these diseases are reported to be associated with menstrual problems. These diseases
affect female reproductive organs like the breast, uterus and ovaries. Estrogen is the main
hormone responsible for the menstrual cycle, so irregular menstruation is primarily due to a
disturbance in estrogen levels. Estrogen imbalance leads to various pathological conditions in
pre-menopausal women, such as endometriosis, breast cancer, colorectal cancer, prostate cancer,
poly cysts, intrahepatic cholestasis of pregnancy, osteoporosis, cardiovascular diseases, obesity,
etc. In this review, we discuss common drug targets and therapeutic strategies for the treatment
of diseases caused by deficient estrogen levels by using acupuncture and compounds of natural
origin.
arsenal. Recent findings show that targeting aurora B itself is sufficient to exhibit anticancer activity. When compared
with other anticancer targets, aurora B has a very limited number of specific inhibitors. Recently GSK1070916 and reversine were discovered as promising new aurora B inhibitors. Amongst these GSK1070916 emerged as the most potent
molecule targeting aurora B. Taking the scaffold of GSK1070916 as a reference, new molecules were designed by isosteric/bioisosteric and fragment based modifications. Furthermore, an accurate cross-platform docking, MM/GBSA based
rescoring, molecular dynamics simulation were carried out to compare the binding conformation and affinities of the designed molecules with the references. Top two designed molecules showed better docking score and a better binding free
energy profile as compared to reversine and GSK1070916 with the best ligand retaining conserved hydrogen bond and
salt bridge interactions with Ala173, Ala233 and Lys122. The binding mode of top two designed ligands is relatively
similar to that of reversine and GSK1070916. Molecular dynamics simulations proved that the identified hits are rather
stable in the enzyme active site pocket, which further confirms the potential of the designed ligands as a specific target for
aurora B.
We believe that findings of this study will provide medicinal chemists with potential markers towards the design of potent
anticancer drug design targeting aurora B and a broad range of aurora kinases.
the cases, these diseases are reported to be associated with menstrual problems. These diseases
affect female reproductive organs like the breast, uterus and ovaries. Estrogen is the main
hormone responsible for the menstrual cycle, so irregular menstruation is primarily due to a
disturbance in estrogen levels. Estrogen imbalance leads to various pathological conditions in
pre-menopausal women, such as endometriosis, breast cancer, colorectal cancer, prostate cancer,
poly cysts, intrahepatic cholestasis of pregnancy, osteoporosis, cardiovascular diseases, obesity,
etc. In this review, we discuss common drug targets and therapeutic strategies for the treatment
of diseases caused by deficient estrogen levels by using acupuncture and compounds of natural
origin.