Drug Discovery Lead Optimization - Report Sample

Intrioduction

A drug discovery program is initiated with the motive of developing a suitable medical product for a disease or clinical condition. This activity starts by identifying the target, which may necessitate additional target validation before progressing to the lead discovery phase. The lead optimization phase aims at maintaining suitable properties in lead compounds and reducing deficits that exist in the structures. The identified lead structures can be altered to advance their specificity and selectivity towards a specific target. Therefore, lead optimization is associated with chemical modification of active molecules to address toxicological, pharmacokinetic, and pharmacodynamic issues to enhance its clinical use. When running a lead optimization program, there are three main properties to put into consideration. These include genotoxicity, absorption of lead compounds, and dose linearity. These properties are prioritized for various reasons.

Is your time best spent reading someone else’s essay? Get a 100% original essay FROM A CERTIFIED WRITER!

Save 25%

Genotoxicity

Genotoxicity can be described as a destructive impact on cells' genetic properties or materials that affect its integrity. Genotoxins can be mutagens, carcinogens, or teratogens. The main aim of genotoxicity testing is whether the substance will affect genetic material or may lead to growth development in various body cells. Earlier testing ensures the control of advancing defenseless forms of life to genotoxic substances (Hughes et al., 2011). The test is used to recognize compounds that directly or indirectly initiate genetic mutilation. Therefore, it essential to carry out genotoxicity tests in the lead optimization phase to evade potential damage that can occur.

Absorption and Dose

Another essential property to consider in the lead optimization phase is the absorption of the compound. The analysis reflects the bioavailability of compounds. The ability to dissolve a compound in a solvent giving homogenous system is an essential parameter. Formulation of oral dosage may be challenging in situations where the drug is insoluble since it limits the absorption of compounds from the gastrointestinal tract. Also, poor solvency affects analyses such as the DMPK (Hughes et al., 2011). Therefore, absorption of the compound is vital in systematic circulation to achieve an anticipated pharmacological response.

Dose linearity is also an important property to consider during the lead optimization phase. Discovering a new drug with linear pharmacokinetic properties is essential in enabling dose and dose schedule adjustment in patients. Linear pharmacokinetics ensures that the time and dose profiles are superimposable. Thus, the assessment of dose proportionality is a significant pharmacokinetic analysis conducted during the lead optimization phase.

Conclusion

To sum up, the lead optimization phase has the role of maintaining significant features of a compound and eradicating the deficits. The main properties prioritized during the lead optimization process include genotoxicity to destroy any potential genes damage, absorption of compounds to enhance the solubility of drugs in blood metabolism, and drug linearity that ensures correct dosage at the precise time range. These properties should be put into consideration when conducting lead optimization during drug discovery processes.

References

Hughes, J. P., Rees, S., Kalindjian, S. B., & Philpott, K. L. (2011). Principles of early drug discovery. British journal of pharmacology. doi: 10.1111/j.1476-5381.2010.01127.x.