A5057661647- Phosphodiesterase function and regulation
- Crystallization and Solubility Studies
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
- Receptor Mechanisms and Signaling
- Theoretical and Computational Physics
- Signaling Pathways in Disease
- Slime Mold and Myxomycetes Research
- Synthesis and biological activity
- Mineralogy and Gemology Studies
- Nanoplatforms for cancer theranostics
- Quinazolinone synthesis and applications
- Catalytic C–H Functionalization Methods
- Bioinformatics and Genomic Networks
- Solidification and crystal growth phenomena
- Protein Structure and Dynamics
- Venomous Animal Envenomation and Studies
- Synthetic Organic Chemistry Methods
- Complex Systems and Time Series Analysis
- Machine Learning in Materials Science
- Adenosine and Purinergic Signaling
- Crystallography and molecular interactions
- Photoacoustic and Ultrasonic Imaging
- Photodynamic Therapy Research Studies
University of Cambridge
2017-2021
GlaxoSmithKline (United Kingdom)
2021
American University of Beirut
2013-2016
University of Arts
2016
Active learning using models built on binding potency predictions from free energy perturbation (AL-FEP) has been proposed as a method for generating machine capable of predicting biochemical early-stage lead optimization where limited measured data are available. Two applications AL-FEP described here different bromodomain inhibitor series that were developed in historic GSK projects: one the core is kept constant and other changes included pool compound ideas. Measured have used to assess...
In silico approaches often fail to utilize bioactivity data available for orthologous targets due insufficient evidence highlighting the benefit such an approach. Deeper investigation into orthologue chemical space and its influence toward expanding compound target coverage is necessary improve confidence in this practice.Here we present analysis of ChEMBL PubChem impact on prediction. We highlight number conflicting bioactivities between human orthologues low annotations are overall...
N-containing quaternary stereocenters represent important motifs in medicinal chemistry. However, due to their inherently sterically hindered nature, they remain underrepresented small molecule screening collections. As such, the development of synthetic routes generate molecules that incorporate this particular feature are highly desirable. Herein, we describe diversity-oriented synthesis (DOS) a diverse collection structurally distinct featuring three-dimensional (3D) motif. The subsequent...
Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at multiple targets is required produce a clinical effect. In particular, suitable compounds be useful neurodegenerative diseases by promoting neuronal survival synergistic manner via their multi-target the adenosine A1 and A2A receptors (A1R A2AR) phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, this work we describe computational method for design of...
Dimeric calpains constitute a promising therapeutic target for many diseases such as cardiovascular, neurodegenerative and ischaemic disease. The discovery of selective calpain inhibitors, however, has been extremely challenging. Previously, allosteric inhibitors calpains, PD150606, which included specific α-mercaptoacrylic acid sub-structure, were reported to bind the penta-EF hand calcium binding domain, PEF(S) calpain. Although these are over other cysteine proteases, their mode action...
Analysis of the molecular and structural features GSK crystal structure database Cambridge Structural Database leads to improved reliability in hydrogen bond propensity models for pharmaceutical polymorphs.
We demonstrate the effective cytotoxic properties of a dye-sensitized metal oxide in an <italic>in vitro</italic> model human lung cancer cell line (A549 cells) upon light irradiation, where type I mechanism photo-dynamic therapy is realized exclusively.
Abstract Enhanced/prolonged cAMP signalling has been suggested as a suppressor of cancer proliferation. Interestingly, two key modulators that elevate cAMP, the A 2A receptor (A R) and phosphodiesterase 10A (PDE10A), are differentially co-expressed in various types non-small lung (NSCLC) cell-lines. Thus, finding dual-target compounds, which simultaneously agonists at R whilst also inhibiting PDE10A, could be novel anti-proliferative approach. Using ligand- structure-based modelling combined...
Liesegang bands are formed when solutions of co-precipitate ions interdiffuse in a 1D gel matrix. In recent study [R. F. Sultan, Acta. Mech. Sin. 27, 119 (2011)], patterns have been characterized as fractal structures. addition to experimentally obtained patterns, geometric were constructed conformity with the well-known empirical laws. Both mathematical dimensions and box count for images PbF2 PbI2 calculated. can also be described by entropy state function, categorized more or less ordered...