The purchased analogue RA-0002723-01

[HadiaAmahli]

RA-0002723 is one of the purchased analogues of the original hit RA-00010017-01, here is its structure:

RA-0002723 showed active active in both gelbased assay and picogreen assay: Gelbased assay data: SARS-RdRp IC50= 14 µm, h-mtRNAP IC50= 109 µm, that means weak selectivity =8. Picogreen assay showed: IC50= 26.88 µm with moderate solubility= 85.45 µm.

We are searching for commercial analogues that could improve the selectivity and the potency of RA-00002723 as well as its solubility (RA_0002723 LogP= 4.05). RA-0002723 have been sent to the aggregation assay and we are looking forward to receiving the data soon.

[HadiaAmahli]

Here are the structure of 16 analogues we ordered on 24th Jan 2024 from Enamine company and supposed to receive them at UCL in 2-3 weeks.

I am also planning to synthesize the following compound and to send all of these analogues to the UNC to be tested.

[HadiaAmahli]

On 15th March 2024, the above purchased and synthetic analogues have been sent for for Gel-based assay (by Dr. Egor Tchesnokov at Götte Laboratory) and Picogreen assay by Dr. Xuelin Bian at Jim Sacchettini lab. See here

Three of these analogues with different ClogP were sent for solubility and aggregation assay.

[HadiaAmahli]

We recently received the aggregation assay data for RA-0002723-01. Unfortunately, this compound having intensity above 1000 kcnt/s or laser power less than 100 are considered aggregators that means this compound showed aggregation.

I don't think we will proceed with this series unless the recently sent analogues as explained above show impressive activity.

[HadiaAmahli]

Unfortunately, the new Picogreen assay data and other data received on 29th May 2024 did not show any improved potency or solubility for the selected analogues above, that's why we decided to close this issue.