Chemistry matters. Join us to get the news you need.

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.


Drug Discovery

STING-activating molecule fights tumors via systemic delivery

Novel compound doesn’t need to be injected directly into tumors

by Bethany Halford
November 9, 2018 | APPEARED IN VOLUME 96, ISSUE 45



Drugmakers have been buzzing about the stimulator of interferon genes, or STING, protein because of its potential to boost the activity of immunotherapy cancer drugs. To date, compounds designed to target STING have been effective only when they’re injected directly into tumors. Scientists at GlaxoSmithKline now report a diamidobenzimidazole molecule (shown) that activates STING and fights tumors in mice when given via intravenous injection (Nature 2018, DOI: 10.1038/s41586-018-0705-y). The researchers, led by Joshi Ramanjulu, initially identified an amidobenzimidazole compound that bound to STING. STING forms a homodimer, made of two identical proteins. When the GSK researchers examined the crystal structure of the two interacting, they found two molecules of the amidobenzimidazole bound to the STING homodimer in proximity. Inspired by this symmetrical structure, they covalently linked two of the compounds with a four-carbon chain, creating a diamidobenzimidazole. This molecule bound to STING 1,000 times more strongly than the unlinked solo compound. They then optimized the structure to make a more potent molecule, which prevented tumors from growing in mice when given systemically by injection.



This article has been sent to the following recipient:

Mark Gebert (December 10, 2018 2:52 PM)
The structure shown in the figure is NOT diamidobenzimidazole. It is an asymmetrical variant of the molecule.
Bethany Halford (December 10, 2018 3:02 PM)
Hi Mark,

Apologies if the label is confusing. It's supposed to refer to the general diamidobenzimidazole core. The authors of the reports refer to these as dimeric amidobenzimidazole STING receptor agonists. The paper is linked in the story.
Thanks for reading closely.

Bethany Halford
Senior Correspondent

Leave A Comment

*Required to comment