| Chemical Properties | Back Directory | [Boiling point ]
954.7±65.0 °C(predicted) | [density ]
1.53±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted) | [solubility ]
Ethanol: Soluble
Methanol: Soluble | [form ]
Solid | [pka]
10.75±0.40(predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
PROTAC HK2 Degrader-1 is a PROTAC consisting of Lonidamine (HY-B0486) as a target protein Hexokinase 2 (HK2) inhibitor and Thalidomide (HY-14658) as a CRBN ligand-linked PROTAC. PROTAC HK2 Degrader-1 selectively inhibits the proliferation of breast cancer cells by forming a ternary complex through the ubiquitin-proteasome system to degrade Hexokinase 2 (HK2) protein leading to mitochondrial damage and cell death. PROTAC HK2 Degrader-1 effectively inhibits breast tumor growth and reduces the colonic side effects of cisplatin for breast cancer research[1]. | [in vivo]
PROTAC HK2 Degrader-1 (50 mg/kg, Intraperitoneal injection, bid, for nine times, into six-weekold female BALB/c mice) inhibits tumor growth in 4T1 tumor models[1].
PROTAC HK2 Degrader-1 (50 mg/kg, Intraperitoneal injection, bid, for nine times, six-weekold female BALB/c mice) can induce GSDME-dependent pyroptosis to realize tumor immune response and effectively inhibit breast tumor growth[1].
PROTAC HK2 Degrader-1 (Cisplatin (HY-17394) 10mg/kg, i.v., C-02 50mg/kg, i.p., 25 days, into six-weekold female BALB/c mice) can sensitize Cisplatin (HY-17394) while reducing the colon side effects of Cisplatin (HY-17394), which has potential clinical value[1]. | Animal Model: | xenograft models , into six-weekold female BALB/c mice[1] | | Dosage: | 50 mg/kg | | Administration: | Intraperitoneal injection, bid, for nine times. | | Result: | Reduced proliferation and damaged nuclei in mouse models.
Increased the levels of Cytokines IL-1β, IFN-γ, and TNF-α significantly and decreased the level of TGF-β and IL-10.
Elevated levels of cleaved-Casp-3 and GSDME-N in tumor tissues of mouse.
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| Animal Model: | breast tumor model in mice by injecting 4T1 cells subcutaneously into six-weekold female BALB/c mice[1] | | Dosage: | Cisplatin (HY-17394) 10mg/kg, 50mg/kg | | Administration: | Cisplatin (HY-17394) (10mg/kg, i.v.), 50mg/kg, i.p., 25 days | | Result: | Inhibited tumor growth and tumor volume.
Decreased HK2 protein level, while co- treated with Cisplatin (HY-17394).
Could alleviate Cisplatin (HY-17394) aggravated colon damage.
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| [References]
[1] Sang R, et al. Degradation of Hexokinase 2 Blocks Glycolysis and Induces GSDME-Dependent Pyroptosis to Amplify Immunogenic Cell Death for Breast Cancer Therapy. J Med Chem. 2023 Jun 27. DOI:10.1021/acs.jmedchem.3c00118 |
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