AK-1690

AK-1690 : Degrader (PROTAC) of STAT6

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe AK-1690 is in the process of SERP review.

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Information

STAT6

Degrader (PROTAC)

up to 1 uM

In Vitro Validations

No in Vitro Validations

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): AK-1690 had no significant effect on STAT1, STAT3, STAT5, and pSTAT5Y694 up to 10 μM. AK-1690 had a modest effect on STAT2 protein at 2 and 10 μM, with a maximum reduction of STAT2 protein of <40%. The levels of STAT4 protein were not detectable in the MV4;11 cell line.

Potency assay, off target (cells): Degradation selectivity of AK-1690 was evaluated on a global level by proteomics. Human PBMCs were treated with AK-1690 at a high concentration (5 μM) for a long duration (18 h).

Probe Selectivity in Cell:

With 18 h treatment at 5 μM, AK-1690 reduced the levels of only four proteins by ≥50% out of >6,000 proteins detected. Specifically, the STAT6 protein level was decreased by 79%, whereas the levels of EPB41L1 (erythrocyte membrane protein band 4.1), KRT1 (Keratin 1), and AKR7A3 (aldo-keto reductase family 7 member A3) were reduced by 60%, 59%, and 51%, respectively. Levels of other members of STAT family proteins (STAT1, STAT2, STAT3, STAT4, STAT5) were not significantly reduced, consistent with our Western blotting data.

Potency assay, off target (cells): Western blot analysis of Jurkat cells treated with 10 uM AK-1690 has no effect on cereblon neo-substrates IKZF1, IKZF2, IKZF3, and GSPT1.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

AK-1690 is a selective STAT6 PROTAC degrader with robust cellular characterization. Target engagement is supported by nanomolar degradation potency, an inactive control analog (AK-1690Me), and competition and neddylation controls consistent with a CRBN-dependent mechanism. Global proteomic analysis indicates selective STAT6 degradation with minimal off-target effects. Used within the recommended concentration range, the probe supports assignment of observed cellular phenotypes to STAT6 degradation.

(last updated: 8 Jan 2026 )