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Updated: Jul 9, 2026

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes
09:54

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

Published on: September 12, 2018

Identification of TYK2 activators. Part 2: Optimization of terminal alkyne substituents to enhance activation potency

Hirokazu Matsumoto1, Tien-Cheng Wang1, Fumio Nakajima1

  • 1Drug Discovery Unit, Carna Biosciences, Inc., Kobe 650-0047, Japan.

Bioorganic & Medicinal Chemistry Letters
|July 7, 2026
PubMed

Insights

Researchers identified a novel Tyrosine Kinase 2 (TYK2) activator, compound 6fg, for potential cancer immunotherapy. This phenylalkyne analog shows potent activation, offering a new strategy to boost antitumor immunity.

Area of Science:

  • Biochemistry
  • Immunology
  • Medicinal Chemistry

Background:

  • Tyrosine Kinase 2 (TYK2) is crucial in immune signaling.
  • TYK2 inhibition treats autoimmune diseases.
  • TYK2 activation may enhance antitumor immunity for cancer immunotherapy.

Purpose of the Study:

  • To identify novel TYK2 activators for cancer immunotherapy.
  • To expand structure-activity relationship (SAR) studies of previously identified TYK2 activators.
  • To explore substituents at the terminal alkyne position of TYK2 activators.

Main Methods:

  • Scaffold-repurposing design strategy based on a known TYK2 inhibitor.
  • JH2 pseudokinase domain docking studies.
  • Structure-activity relationship (SAR) exploration of alkyne-containing TYK2 activators.

Main Results:

  • Compound 2, an alkyne-containing derivative, was identified as a novel TYK2 activator.
  • Phenylalkyne analog 6fg emerged as the most potent activator.
  • Compound 6fg demonstrated an EC50 of 0.21 μM and a 7.8-fold maximal activation effect (Emax).

Conclusions:

  • The phenylalkyne analog 6fg is a highly potent TYK2 activator.
  • This finding supports TYK2 activation as a promising strategy in cancer immunotherapy.
  • Further development of TYK2 activators could lead to new cancer treatments.
Keywords:
ActivatorPseudokinase domainStructure activity relationshipTYK2

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