ArticleACS medicinal chemistry letters2026
Discovery of MK-2118, a Small-Molecule Agonist of STING.
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Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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45 authors.
Timothy Henderson†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Michael D Altman†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Alexei V Buevich†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.ORCID https://orcid.org/0000-0002-5968-9151
Brandon Cash†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Saso Cemerski†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Wonsuk Chang†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.ORCID https://orcid.org/0000-0003-4697-4663
Yiping Chen†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Matthew Childers†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Jared Cumming†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Peter J Dandliker†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Guo Feng†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Andrew Haidle†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Robert P Hayes†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Thu Ho†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
James P Jewell†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Ilona Kariv†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Ian Knemeyer†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Johnny Kopinja†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Brian M Lacey†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Jason Laskey†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Charles A Lesburg†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Rui Liang†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Jongwon Lim†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Brian J Long†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Min Lu†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.ORCID https://orcid.org/0000-0003-0378-9134
Yanhong Ma†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Ellen C Minnihan†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.ORCID https://orcid.org/0000-0003-1946-190X
Ryan D Otte†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Gregory O'Donnell†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Bo-Sheng Pan†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Samanthi A Perera†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Jennifer A Piesvaux†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Jeremy P Presland†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Laura Price†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Larissa Rakhilina†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Berengere Sauvagnat†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Gottfried K Schroeder†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Sharad Sharma†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
B Wesley Trotter†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Sriram Tyagarajan†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Hyun Woo†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Daniel F Wyss†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Serena Xu†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
George H Addona†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
David Jonathan Bennett†Department of Discovery Chemistry; ‡Department of Quantitative Biosciences; §Department of Discovery Oncology; ∥Department of Pharmacokinetics; ⊥Department of Discovery Pharmaceutical Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Agonists of Stimulator of Interferon Genes (STING) have the potential to activate the innate and adaptive immune system for cancer treatment. Early efforts in identifying suitable therapeutics were focused on cyclic dinucleotide (CDN) analogs of 2',3'-cGAMP, the endogenous ligand to STING. CDNs lack of tractable bioavailability led us to consider small-molecule modulators of STING. We previously reported the identification of MSA-2, an orally available non-nucleotide STING agonist with antitumor activity. Optimization efforts in this series faced challenges with uniform activity across species, cell shift, and steep structure activity relationships. Herein we report lead optimization efforts guided by structure-based drug design to identify the MSA-2 analog MK-2118.
Indexed as
Drug DiscoveryImmunotherapyMK-2118OncologySTING
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