Related Experiment Video

Updated: May 28, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
07:16

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission

Published on: August 16, 2018

Discovery of Dual A2A/A2B Adenosine Receptor Antagonist and Clinical Candidate INCB106385

Chao Qi1, Matthew S McCammant1, Yong Li1

  • 1Incyte Research Institute, Incyte Corporation, Wilmington, Delaware19803, United States.

Journal of Medicinal Chemistry
|May 27, 2026
PubMed

Insights

A new drug, INCB106385, targets adenosine receptors to enhance cancer immunotherapy. This potent dual antagonist shows promise in preclinical models, advancing to Phase 1 clinical trials.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Immune checkpoint suppression allows tumor cells to evade immune responses.
  • Adenosine in the tumor microenvironment activates A2A receptors, hindering immune function.
  • Existing A2A antagonists may lack sufficient potency against high local adenosine levels.

Purpose of the Study:

  • To discover and characterize a novel dual A2A/A2B adenosine receptor antagonist.
  • To evaluate the preclinical efficacy and pharmacokinetic properties of the novel compound INCB106385.
  • To support the clinical development of INCB106385 for cancer immunotherapy.

Main Methods:

  • In-house screening to identify dual A2A/A2B antagonists.
  • In vitro and in vivo preclinical studies to assess compound properties and efficacy.
  • Pharmacokinetic and pharmacodynamic assessments across multiple species.

Main Results:

  • Discovery of INCB106385 (compound 36), a potent dual A2A/A2B antagonist.
  • INCB106385 demonstrated favorable drug-like properties and limited central nervous system penetration.
  • Significant efficacy was observed in a CT26 mouse colon carcinoma model with robust pharmacokinetics.

Conclusions:

  • INCB106385 is a potent dual A2A/A2B antagonist with promising preclinical results.
  • The compound's properties support its advancement into Phase 1 clinical trials for cancer immunotherapy.
  • Targeting adenosine receptors offers a potential strategy to overcome immune suppression in cancer.

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