*7.3.1 ADME*

*Cheminformatics and Its Applications*

*7.1.3.2 Surface plasmon resonance (SPR)*

have been appraised in several publications [71].

*7.2.1 Tools of preclinical drug development*

It can ascertain the binding sites and modes of ligand binding to protein [68].

Surface plasmon resonance is known as a nonlabel technology that can identify, screen, and quantify intermolecular interactions in actual time. It is applied to quantify binding affinities. SPR-dependent biosensors work by detecting the ligands and immobilized target molecular interactions and supply appropriate information on kinetics of biomolecular interactions. The output information can be utilized to provide comprehensive functional data on binding actions such as specificity, kinetics, concentration, and affinity [69]. Scientific literature study revealed Biacore tools as mainly used SPR technology at commercial

In the last 2 years, different methodologies based on high-throughput screening and their combinations with chemistry have been developed in order to manufacture versatile compounds by limiting the resources. Among these methodologies, several other in vitro and in silico supplementary approaches have also come forward for the identification and potential evaluation of these compounds as lead candidate validation. Those compounds which are selected as "hits" during this screening procedure are further analyzed and subjected to in vivo toxicity and efficacy profiling. During preclinical stage of drug development, simple formulation approaches are favored. Combinatorial chemistry and high-throughput approaches

PLOTs are preclinical lead optimization technologies that should be rapid enough to edge with high-throughput discovery screenings without causing further delay and should be predictive and cost-effective. PLOT platform usually comprised of in vitro systems, small and acquiescent to mechanization, and that is why it is easy to achieve the mandatory throughput with minimum use of

Selection of methodology and tools for selection of preclinical drug candidates is a rigorous process. Sequential approach of preclinical to clinical is practiced to sort out the long list of target selected compounds. This streamline strategy provides with deeper understanding of action of the drug prior to its progress to the next steps [73].

*7.2.2 Pharmacokinetics and pharmacodynamics (PK/PD) during preclinical drug* 

Pharmacodynamics involves the study of effect of drug in dose- and timedependent manner. Pharmacokinetics is the study of absorption, metabolization, distribution, and excretion of a drug over time. PK/PD is a program at early phase of lead drug development which acts as a bridge between drug discovery and preclinical drug development. This stage set aims for further development activities, and information obtained at this stage act as a key to

*7.1.3.1 X-ray crystallography*

levels [70].

**7.2 Preclinical trials**

compound use [72].

*evaluation*

subsequent steps.

**138**

This is the final stage of preclinical trials; after this the optimized drug is further processed towards the clinical trial. Absorption, distribution, metabolism, and excretion screening is performed at this stage. The primary goal of ADME is to develop a competitive drug with adequate safety avoiding PK failure in clinical phase.
