SH-26
SH-26 is a PHD1 PROTAC degrader with DC50s of 1.06 μM, 4.16 μM and 4.91 μM in MDA-MB-231, HepG2 and HEK-293T cells, respectively. SH-26 recruits CRBN to induce PHD1 degradation via the ubiquitin-proteasome system. SH-26 attenuates APAP (HY-66005)-triggered ROS accumulation, mitochondrial dysfunction, and NLRP3 inflammasome activation. SH-26 can be used for the research of acute liver injury.
(Pink: HIF/HIF Prolyl-Hydroxylase ligand (HY-183996); Blue: Cereblon ligand (HY-10984); Black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C38H41N9O8
- Peso molecular:751.79
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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NLRP3 inflammasome |
PHD1 |
SH-26 (Compound 26) (0.25-10 μM; 2-72 h) induces concentration- and time-dependent PHD1 degradation in MDA-MB-231 cells, with a DC50 of 1.06 μM and a Dmax of 77.5% in 48 h[1].
SH-26 (0.25-50 μM; 48 h) induces concentration-dependent PHD1 degradation in HepG2 cells with a DC50 of 4.16 μM[1].
SH-26 (0-50 μM; 48 h) induces concentration-dependent PHD1 degradation in HEK-293T cells with a DC50 of 4.91 μM[1].
SH-26 (2-25 μM; 48 h) mediates PHD1 degradation in MDA-MB-231, HepG2, and HEK-293T cells in a ubiquitin-proteasome system-dependent manner that requires both PHD1 target engagement and CRBN recruitment[1].
SH-26 (1-25 μM; 4 h pretreatment) degrades PHD1 and PHD2 (but not PHD3) and stabilizes HIF-1α in APAP-challenged AML12 hepatocytes under normoxic conditions[1].
SH-26 (1-25 μM; 4 h pretreatment) exhibits enhanced concentration-dependent PHD1 degradation (DC50 = 0.13 μM) and stabilizes HIF-1α in APAP-challenged AML12 hepatocytes under hypoxic conditions[1].
SH-26 (1-50 μM; 4 h pretreatment) protects AML12 hepatocytes from APAP-induced injury in a concentration-dependent manner without inherent cytotoxicity[1].
SH-26 (1-25 μM; 4 h pretreatment) restores expression of HIF-1α target genes BNIP3 and SLC2A1, does not affect PHD1 mRNA levels, and suppresses IL-1β mRNA levels in APAP-challenged AML12 hepatocytes[1].
SH-26 (1-50 μM; 4 h pretreatment) dose-dependently degrades PHD1 and suppresses IL-1β protein levels in APAP-challenged AML12 hepatocytes[1].
SH-26 (1 μM; 24 h) degrades PHD1 and downregulates pro-inflammatory mediators IL-1β, IL-6, and TNF-α in LPS (HY-D1056)+IFN-γ-stimulated THP-1-derived M1 macrophages[1].
SH-26 (1-25 μM; 4 h pretreatment) dose-dependently reduces mitochondrial reactive oxygen species accumulation in APAP-challenged AML12 hepatocytes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:0.25μM; 0.5 μM; 1 μM; 2 μM; 2.5 μM; 5 μM; 10 μM
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Incubation Time:2 h; 4 h; 8 h; 12 h; 24 h; 48 h; 72 h
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Result:Induced 67% PHD1 degradation at 24 h, 70% at 48 h, and 80% at 72 h at 2 μM.
Induced concentration-dependent PHD1 degradation with a DC50 of 1.06 μM and a maximum degradation (Dmax) of 77.5%.
Caused significant degradation within 4 h, with maximal depletion achieved by 72 h.
Showed no hook effect at concentrations up to 10 μM.
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Cell Line:HepG2 hepatoma cells
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Concentration:0.25μM; 0.5 μM; 1 μM; 2.5 μM; 5 μM; 10 μM
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Incubation Time:48 h
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Result:Induced concentration-dependent PHD1 degradation with a DC50 of 4.16 μM.
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Cell Line:HEK-293T embryonic kidney cells
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Concentration:0.25μM; 0.5 μM; 1 μM; 2.5 μM; 5 μM; 10 μM
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Incubation Time:48 h
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Result:Induced concentration-dependent PHD1 degradation with a DC50 of 4.91 μM.
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Cell Line:MDA-MB-231, HepG2, and HEK-293T cells
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Concentration:2 μM; 25 μM
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Incubation Time:48 h
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Result:Had its PHD1-degrading activity blocked in all three cell lines when cotreated with MG132, MLN4924, Takeda-54, or SH-28.
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Cell Line:AML12 hepatocytes
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Concentration:1 μM; 2.5 μM; 5 μM; 10 μM; 25 μM
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Incubation Time:4 h pretreatment
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Result:Degraded PHD1 in a concentration-dependent manner.
Degraded PHD2 with a DC50 of 1.83 μM and a Dmax of 71.8%.
Did not degrade PHD3.
Stabilized HIF-1α in a concentration-dependent manner.
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Cell Line:AML12 hepatocytes
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Concentration:1 μM; 2.5 μM; 5 μM; 10 μM; 25 μM
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Incubation Time:4 h pretreatment
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Result:Exhibited enhanced PHD1 degradation under hypoxia with a DC50 of 0.13 μM.
Stabilized HIF-1α in a concentration-dependent manner.
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Cell Line:AML12 hepatocytes (APAP-induced injury)
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Concentration:1 μM; 2.5 μM; 5 μM; 10 μM; 25 μM; 50 μM
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Incubation Time:4 h pretreatment
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Result:Attenuated APAP-induced hepatotoxicity in a concentration-dependent manner.
Exhibited no inherent cytotoxicity at tested concentrations.
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Cell Line:AML12 hepatocytes (APAP-induced injury)
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Concentration:1 μM; 5 μM; 25 μM
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Incubation Time:4 h pretreatment
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Result:Restored BNIP3 mRNA to baseline levels and significantly upregulated SLC2A1 mRNA at 10 μM.
Did not alter PHD1 mRNA levels.
Dose-dependently suppressed IL-1β mRNA levels.
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Cell Line:AML12 hepatocytes (APAP-induced injury)
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Concentration:1 μM; 2.5 μM; 5 μM; 10 μM; 25 μM; 50 μM
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Incubation Time:4 h pretreatment
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Result:Dose-dependently degraded PHD1.
Dose-dependently suppressed IL-1β protein levels.
| Species | Dose | Route | Cmax | Tmax | Plasma Concentration |
|---|---|---|---|---|---|
| Mice[1] | 30 mg/kg | i.p. | 7 μM | 0.5 h | ~10 nM |
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, 8 weeks old, APAP-induced acute liver injury)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:i.p.; single dose
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Result:Significantly reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), and blood urea nitrogen (BUN) at 30 mg/kg.
Markedly attenuated APAP-induced hepatic damage, confirmed by histopathological analysis and necrotic area quantification at 10 mg/kg and 30 mg/kg.
Effectively reversed APAP-induced upregulation of PHD1 protein expression and induced robust PHD1 degradation in liver tissue at 10 mg/kg and 30 mg/kg.
Significantly reduced the upregulation of inflammasome components (NLRP3, GSDMD, cleaved caspase 1, cleaved IL-1β) at 10 mg/kg and 30 mg/kg.
Attenuated pro-apoptotic signals (increased BAX/BCL2 ratio, elevated cleaved caspase 3 levels) at 10 mg/kg and 30 mg/kg.
Significantly reduced liver tissue expression of immune cell markers LY6G, F4/80, CD31, and CD3 at 10 mg/kg and 30 mg/kg.
Chemical Information
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Peso molecular 751.79
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Fòrmula C38H41N9O8
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SMILES
O=C1N(C(C2=CC=CC(NCCOCCOCCOCCNC(CCNC3=CC4=NC=NN4C(C5=C(C=C(C=C5)C#N)C)=C3)=O)=C21)=O)C6CCC(NC6=O)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SH-26 Related Classifications
HY-183995 Related Classifications
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- SH-26
- SH26
- SH 26
- PROTACs
- HIF/HIF Prolyl-Hydroxylase
- Reactive Oxygen Species (ROS)
- NOD-like Receptor (NLR)
- ubiquitin-proteasome system
- NLRP3 inflammasome
- MDA-MB-231 cells
- AML12 hepatocytes
- THP-1-derived M1 macrophages
- HepG2 cells
- PHD1
- cereblon
- HEK-293T cells
- APAP-induced acute liver injury model
- Inhibitor
- inhibitor
- inhibit