DUBTACs
Deubiquitinase-targeting chimeras
Deubiquitinase-targeting chimeras (DUBTACs), a class of heterobifunctional protein stabilizers consisting of deubiquitinase (DUB) and protein-of-interest (POI) targeting ligands conjugated with a linker, can rescue such proteins from aberrant elimination. DUBTACs stabilize the levels of POIs in a DUB-dependent manner, removing ubiquitin from polyubiquitylated and degraded proteins. DUBTACs can induce a new interaction between POI and DUB by forming a POI-DUBTAC-DUB ternary complex. The chemically induced proximity of a DUB with a POI by the DUBTAC promotes the removal of polyubiquitin chains attached to the POI to block proteasome-mediated degradation, thereby stabilizing and elevating the level of the POI with protective functions. Rescuing the POIs by DUBTACs from aberrant degradation provides therapeutic potential for the treatment of various diseases.
References:
- [1]. Ma Z, et al. Deubiquitinase-Targeting Chimeras (DUBTACs) as a Potential Paradigm-Shifting Drug Discovery Approach. J Med Chem. 2025 Apr 10;68(7):6897-6915. [Content Brief]
- [2]. Henning NJ, et al. Deubiquitinase-targeting chimeras for targeted protein stabilization. Nat Chem Biol. 2022 Apr;18(4):412-421. [Content Brief]
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DUBTACs Related Products (15)
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FXR DUBTAC modulator-1
0 ImagesCat. No.: HY-182350CAS No.: 3081876-96-9FXR DUBTAC modulator-1 is a deubiquitinase-targeting chimeric molecule (DUBTAC) that targets FXR, with a Ka value of 2.12e-5 M for FXR. FXR DUBTAC modulator-1 recruits the deubiquitinase OTUB1, binds to OTUB1 and forms a ternary complex with FXR, reduces the polyubiquitination level of FXR, prevents FXR degradation via the ubiquitin-proteasome pathway, and elevates the protein level of FXR. FXR DUBTAC modulator-1 can be used in the research of cholestatic liver injury.
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p53 Y220C ligand-1
0 ImagesCat. No.: HY-180619p53 Y220C ligand-1(compound PK-A) is a target protein ligand of p53 DUBTAC modulator-1 (HY-180618). p53 Y220C ligand-1 exhibits potent activity in inhibiting cell proliferation in Huh7 cells.
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p53 DUBTAC modulator-1
0 ImagesCat. No.: HY-180618p53 DUBTAC modulator-1 (Compound A1) is a p53 Y220C DUBTAC modulator (Kd = 12.09 µM). p53 DUBTAC modulator-1 effectively reactivates and deubiquitinates mutant p53 Y220C. p53 DUBTAC modulator-1 upregulates p53 Y220C protein levels. p53 DUBTAC modulator-1 induces Apoptosis, reduces Bcl-2, inhibits Wnt signaling. p53 DUBTAC modulator-1 has anti-cancer activity against liver cancer.
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LEB-03-145
0 ImagesCat. No.: HY-143340CAS No.: 2858812-90-3
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cGAS-IN-5-CH2-COOH
0 ImagesCat. No.: HY-187079CAS No.: 3060522-40-6
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MS5128
0 ImagesCat. No.: HY-183725CAS No.: 3060520-82-0MS5128 is an OTUB1-based deubiquitinase-targeting chimera (DUBTAC) targeting CFTR. MS5128 recruits OTUB1 to CFTR to induce deubiquitination and stabilization of CFTR. MS5128 can be used for the research of cystic fibrosis. (Blue: CFTR Ligand (HY-183724); Pink: OTUB1 Ligand (HY-13262); Black: Linker)
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MS6178
0 ImagesCat. No.: HY-185122CAS No.: 3060520-53-5
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MS8588
0 ImagesCat. No.: HY-162967CAS No.: 3060519-94-7MS8588 is a deubiquitinase-targeting chimera (DUBTAC) against cGAS. MS8588 induces targeted stabilization of cGAS, thereby activating downstream signaling pathways. MS8588 activates the cGAS/STING/IRF3 innate immune signaling pathway. MS8588 exhibits antitumor activity.
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LEB-03-153
0 ImagesCat. No.: HY-143343CAS No.: 2858812-88-9
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MS7829
0 ImagesCat. No.: HY-162966CAS No.: 3060519-67-4MS7829 is a deubiquitinase-targeting chimera (DUBTAC) that targets cGAS. MS7829 recruits OTUB1 to cGAS, binds covalently to OTUB1, stabilizes the protein abundance of cGAS, and activates the cGAS-STING-IRF3 innate immune signaling pathway in an OTUB1-dependent manner. MS7829 is applicable to cancer-related research.
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