PROTAC SAMHD1 Degrader-1
PROTAC SAMHD1 Degrader-1 is an orally active targeted SAMHD1 PROTAC degrader, with an IC50 of 6.3 μM against the dNTP hydrolase activity of SAMHD1. PROTAC SAMHD1 Degrader-1 binds to SAMHD1 inside cells and mediates its degradation, with low off-target effects. PROTAC SAMHD1 Degrader-1 inhibits the production of pro-inflammatory cytokines and interferes with the cascade amplification process of inflammatory responses. PROTAC SAMHD1 Degrader-1 delays the progression of pulmonary fibrosis and exerts protective effects on lung tissues. PROTAC SAMHD1 Degrader-1 can be used in pulmonary fibrosis-related research.
(Pink: SAMHD1 ligand (HY-182973); Blue: DCAF1 ligand (HY-182974); Black: linker (HY-W067705)).
For research use only. We do not sell to patients.
- Formula: C54H67ClFN13O8
- Molecular Weight:1080.64
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
PROTAC SAMHD1 Degrader-1 (compound NP12) (0.15-10.0 μM; 6-48 h) induces dose- and time-dependent degradation of SAMHD1 in THP-1 cells, with a DC50 of 1.2 μM[1].
PROTAC SAMHD1 Degrader-1 (10 μM; 24 h pretreatment) increases the sensitivity of wild-type THP-1 cells to Ara-C, reducing the IC50 of Ara-C from 5.4 μM to 1.1 μM, which confirms that it inhibits SAMHD1 activity in cells[1].
PROTAC SAMHD1 Degrader-1 (1-10 μM; 1 h pretreatment) suppresses the production of LPS (HY-D1056)-induced proinflammatory cytokines (IL-1β, IL-6, TNF-α) in RAW264.7 macrophages in a concentration-dependent manner, and interferes with the transcription, translation and secretion of cytokines[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:THP-1 human acute monocytic leukemia cells
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Concentration:0.15, 0.3, 0.6, 1.2, 2.5, 5.1, 10.0 μM
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Incubation Time:6 h, 24 h, 48 h
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Result:Induced 47.9%, 74.4%, and 91.8% SAMHD1 degradation at 1 μM, 2.5 μM, and 5 μM for 48 h, respectively.
Showed dose-dependent degradation across 0.15-10.0 μM for 48 h, with a DC50 of 1.2 μM.
Achieved 66% degradation at 24 h and maximum 89% degradation at 48 h with 5 μM treatment.
Maintained suppressed SAMHD1 levels for at least 24 h post-withdrawal of 5 μM treatment, with levels returning to near initial levels by 48 h post-withdrawal.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 6-8 weeks old, 18-22 g, intratracheal bleomycin-induced pulmonary fibrosis)[1]
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Dosage:20 mg/kg; 40 mg/kg; 80 mg/kg
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Administration:i.g.; daily; 14 days
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Result:Showed gradual body weight recovery from day 9 onward.
Reduced bleomycin-induced lung tissue damage, including alleviated alveolar atrophy/collapse, bronchial wall thickening, and inflammatory cell infiltration.
Decreased collagen fiber deposition in a dose-dependent manner.
Significantly downregulated lung tissue expression of α-smooth muscle actin and fibronectin in a dose-dependent manner.
Reduced serum and bronchoalveolar lavage fluid levels of proinflammatory and profibrotic cytokines (IL-1β, IL-6, TGF-β1), with the 80 mg/kg dose showing the most pronounced effects.
Reduced lung tissue SAMHD1 protein levels to 80.7% (20 mg/kg), 58.3% (40 mg/kg), and 21.9% (80 mg/kg) of the control group, demonstrating dose-dependent degradation.
Chemical Information
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Molecular Weight 1080.64
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Formula C54H67ClFN13O8
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SMILES
OCCCCN(N=C1)C(N=C2NC(CC3)CCN3CC(C=C4)=CC(Cl)=C4OC5=CC(NC(COCCOCCOCC(N(CC6)CCN6C7=CC(N[C@@H](C8)CCCN8C9=CC(F)=CC=C9)=NC=N7)=O)=O)=CC=C5)=C1C(N2)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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