dWIZ-1 

dWIZ-1 is an orally active molecular glue and chemical probe targeting the WIZ transcription factor, which based on an IMiD backbone, binding to human WIZ with an affinity of 3.5 μM. dWIZ-1 recruits WIZ to the cereblon-DDB1 complex via its ZF7 domain, thereby triggering proteasome-dependent degradation of WIZ. dWIZ-1 significantly induces fetal hemoglobin expression in erythroblasts while reducing the level of inhibitory H3K9 dimethylation at WIZ binding sites such as the β-globin locus. Meanwhile, dWIZ-1 does not affect the proliferation and differentiation of erythroblasts, and no cytotoxicity is observed in in vitro cells or cynomolgus monkey models. dWIZ-1 serves as a critical tool molecule for investigating the mechanism and underlying pathways of sickle cell disease^[1][2].

dWIZ-1 (10^-5-10² μM; 18 h) induces dose-dependent degradation of wild-type HiBiT-tagged WIZ in 293T cells, with WIZ(ZF7) identified as the critical domain for this activity^[1].
dWIZ-1 (10 μM, 10^-5-10 μM, 10^-4-10 μM; 6 h, 24 h, 7 days of differentiation) induces CRBN-dependent degradation of endogenous WIZ (DC₅₀=13 nM over 24 hours) and HbF expression (EC₅₀=100 nM over 7 days of differentiation) in primary human CD34⁺ cell-derived erythroblasts, while preserving cell proliferation and differentiation^[1].
dWIZ-1-mediated WIZ degradation reduces repressive H3K9me2 chromatin marks at the β-globin locus in primary human erythroblasts^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

399.48

C₂₂H₂₉N₃O₄

Solid

Off-white to light yellow

O=C([C@@H](N(CC1=C2C=CC(O[C@@H]([C@@H]3N(CC)CCCC3)C)=C1)C2=O)CC4)NC4=O

Room temperature in continental US; may vary elsewhere.

• [1]. Liu J, Shen Z, Park S Y, et al. Discovery of A Small Molecule non-IMiD Degrader of ZBTB7A for the Treatment of β-beta-hemoglobinopathies[J]. bioRxiv, 2025: 2025.09. 17.676148.

  [2]. Ting PY, et al. A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction. Science. 2024;385(6704):91-99.  [Content Brief]