# When Unsuspected Crystallinity Ruins Biological Testing in Early Discovery: A Case Study

## TL;DR

A drug's crystalline form can lead to misleading biological test results due to lower solubility, as shown in a tyrosine kinase inhibitor case.

## Contribution

Highlights the importance of considering crystallinity in early drug discovery to avoid false negatives in biological testing.

## Key findings

- A crystalline tyrosine kinase inhibitor showed false negative biological results due to low solubility.
- The amorphous form of the same compound exhibited better solubility and expected biological activity.
- The discrepancy was resolved by analyzing the physical form of the solid samples.

## Abstract

The impact of the crystalline or amorphous structure of a solid on the solubility and pharmacokinetic properties of a drug candidate is always considered by the pharmaceutical industry during the development of a new drug; however, it is not so frequently considered during the early drug discovery process by organic and medicinal chemists, particularly those working in academia. We want to share, as an example, the false negative obtained in the biological testing of a solid sample of a tyrosine kinase inhibitor due to its unexpected crystallinity and lower solubility with respect to a solid amorphous batch of the same compound and the experimentation carried out to establish the origin of such a discrepancy.