IC50 and toxicity data of RA-0020083-01 analogues

[HadiaAmahli]

5 analogues of RA-0020083-01 shipped to the Nick Heaton lab on 23rd Aug 2023 to be evaluated for their toxicity and bioactivity see here. They showed non toxic and the compound RA-0138504-02 showed an impressive activity ~2 µM. Similar compound has been purchased twice from Mcule and Enamine showed higher IC50 value, we assume this result is related to the high purity of the compound RA-0138504-02 that’s synthesized in house-at UCL by Hadia. You can find the toxicity and bioactivity data as follows:

UCL Drugs 0828 Toxicity and IC50 Data (1).xlsx

UCL Drugs 0828 Toxicity and IC50 Data (2).xlsx

These data confirm that we are on the right path in terms of analogues optimisation plan.

[HadiaAmahli]

The compound RA-0138504-02 is considered our hit to lead, we decided to make and purchase analogous for SAR study and expansion as follows: Purchased analogues:

Synthetic analogues:

[HadiaAmahli]

In the target meeting which held on 15th Nov 2024, we discussed the synthesis of multiple analogues of the lead hit RA-0138504-02, these analogues have been made at UCL by Hadia and to be shipped next week to Duke University to study their activity and toxicity.

Here is the synthetic route adopted to make the right hand side expansion: The purification of the final compounds was challenging due to the UV invisible impurities.

Regarding the left hand side expansion for the lead hit RA-0138504-02, different types of chemistry have been carried out to get new compounds that might help to enhance the activity.