1. JAK/STAT Signaling Stem Cell/Wnt Immunology/Inflammation Apoptosis NF-κB Metabolic Enzyme/Protease
  2. STAT Pyroptosis Apoptosis Reactive Oxygen Species (ROS) c-Myc Bcl-2 Family TrxR
  3. 8α-Tigloyloxyhirsutinolide 13-O-acetate

8α-Tigloyloxyhirsutinolide 13-O-acetate  (Synonyms: 8αTGH)

製品番号: HY-138071 純度: 95.0%
COA 取扱説明書 Technical Support

8α-Tigloyloxyhirsutinolide 13-O-acetate (8αTGH) is a potent and orally active STAT3 inhibitor. 8α-Tigloyloxyhirsutinolide 13-O-acetate induces early oxidative stress and pyroptosis, and late DNA damage, cell cycle arrest, apoptosis in the TNBC cells. 8α-Tigloyloxyhirsutinolide 13-O-acetate suppresses tumor cell growth in vitro and tumor growth in vivo.

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8α-Tigloyloxyhirsutinolide 13-O-acetate

8α-Tigloyloxyhirsutinolide 13-O-acetate 構造式

CAS 番号 : 83182-58-5

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製品説明

8α-Tigloyloxyhirsutinolide 13-O-acetate (8αTGH) is a potent and orally active STAT3 inhibitor. 8α-Tigloyloxyhirsutinolide 13-O-acetate induces early oxidative stress and pyroptosis, and late DNA damage, cell cycle arrest, apoptosis in the TNBC cells. 8α-Tigloyloxyhirsutinolide 13-O-acetate suppresses tumor cell growth in vitro and tumor growth in vivo[1][2].

IC50 & Target

STAT3

 

Bcl-2

 

Bcl-xL

 

Mcl-1

 

Cellular Effect
Cell Line Type Value Description References
HEK293 IC50
0.6 μM
Compound: 4
Inhibition of TNFalpha-induced NF-kappaB activity expressed in human HEK 293 cells after 6 hrs by luciferase reporter gene assay
Inhibition of TNFalpha-induced NF-kappaB activity expressed in human HEK 293 cells after 6 hrs by luciferase reporter gene assay
[PMID: 22850207]
MCF7 IC50
10.4 μM
Compound: 6
Antiproliferative activity against human MCF7 cells for 72 hrs by cyquant assay
Antiproliferative activity against human MCF7 cells for 72 hrs by cyquant assay
[PMID: 26331426]
MDA-MB-231 IC50
1.8 μM
Compound: 6
Antiproliferative activity against human MDA-MB-231 cells for 72 hrs by cyquant assay
Antiproliferative activity against human MDA-MB-231 cells for 72 hrs by cyquant assay
[PMID: 26331426]
NIH3T3 IC50
2 μM
Compound: 6
Cytotoxicity against mouse NIH/3T3 cells after 72 hrs by cyquant cells
Cytotoxicity against mouse NIH/3T3 cells after 72 hrs by cyquant cells
[PMID: 26331426]
RAW264.7 IC50
2 μM
Compound: 4
Antiinflammatory activity against LPS-induced NO production in mouse RAW264.7 cells assessed as reduction in nitrite level preincubated for 15 mins prior to LPS treatment by Griess method
Antiinflammatory activity against LPS-induced NO production in mouse RAW264.7 cells assessed as reduction in nitrite level preincubated for 15 mins prior to LPS treatment by Griess method
[PMID: 22850207]
SF-295 IC50
7.5 μM
Compound: 6
Antiproliferative activity against human SF295 cells for 72 hrs by cyquant assay
Antiproliferative activity against human SF295 cells for 72 hrs by cyquant assay
[PMID: 26331426]
U-251 IC50
1.7 μM
Compound: 6
Antiproliferative activity against human U251MG cells for 72 hrs by cyquant assay
Antiproliferative activity against human U251MG cells for 72 hrs by cyquant assay
[PMID: 26331426]
U-251 IC50
2.2 μM
Compound: 6
Inhibition of Stat3 dimer DNA binding activity in human U251MG cells nuclear extract after 1.5 hrs by EMSA using radiolabeled probe hSIE
Inhibition of Stat3 dimer DNA binding activity in human U251MG cells nuclear extract after 1.5 hrs by EMSA using radiolabeled probe hSIE
[PMID: 26331426]
U-373MG ATCC IC50
2.3 μM
Compound: 6
Inhibition of Stat3 dimer DNA binding activity in human U373MG cells nuclear extract after 1.5 hrs by EMSA using radiolabeled probe hSIE
Inhibition of Stat3 dimer DNA binding activity in human U373MG cells nuclear extract after 1.5 hrs by EMSA using radiolabeled probe hSIE
[PMID: 26331426]
U-373MG ATCC IC50
3.5 μM
Compound: 6
Antiproliferative activity against human U373MG cells for 72 hrs by cyquant assay
Antiproliferative activity against human U373MG cells for 72 hrs by cyquant assay
[PMID: 26331426]
体外実験

8α-Tigloyloxyhirsutinolide 13-O-acetate (R001) (0-30 μM, 72 h) dose-dependently suppresses the viable cell numbers of the human cancer lines[1].
8α-Tigloyloxyhirsutinolide 13-O-acetate (0-10 μM, 0-24 h) leads to early pyroptosis and late DNA damage, cell cycle arrest, and apoptosis only in the TNBC cells[1].
8α-Tigloyloxyhirsutinolide 13-O-acetate (0-20 μM, 0-48 h) promotes ROS induction in triple-negative breast cancer cells[1].

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

Cell Proliferation Assay[1]

Cell Line: Multiple human cancer lines, normal human breast epithelial cells and normal human brain microvascular endothelial cells (HBMEC)
Concentration: 0, 1, 2.5, 5, 10, 20, 30 μM
Incubation Time: 72 h
Result: Dose-dependently suppressed the viable cell numbers of the human cancer lines, MDA-MB-468, MDA-MB-231, Panc-1, A549, DU145, HCC1937, and MDA-MB-436 cells with IC50 values of 2.3, 4.4, 4.3, 5.2, 5.8, 6.3, and 7.1 µM, respectively, compared to much weaker effects on the normal human breast epithelial cells, MCF-10A or HBMEC, with IC50 of 23.9 or 14.2 µM, respectively.

Western Blot Analysis[1]

Cell Line: NIH3T3/v-Src fibroblasts, MDA-MB-231, MDA-MB-468, or MCF-10A cells
Concentration: 0, 2, 5, 10, 20 μM
Incubation Time: 30 min, 3 h, 24 h
Result: Suppressed STAT3:STAT3 DNA-binding activity, with IC50 of 5 µM. Showed the inhibition of STAT3 Tyr phosphorylation in time- and dose-dependent manner, while phospho-Ser-STAT3 (pS727-STAT3), pY1068EGFR, and pY-Jak2 were largely unaffected. Attenuated the expression of STAT3 downstream target genes, including c-Myc, Mcl-1, Bcl-2, Bcl-xL, and vascular endothelial growth factor (VEGF) in MDA-MB-468 and MDA-MB-231 cells.

Apoptosis Analysis[1]

Cell Line: Triple-negative breast cancer (TNBC), MDA-MB-231 and MDA-MB-468 cells, or normal human breast epithelial cells, MCF-10A
Concentration: 0, 2.5, 5 or 10 µM
Incubation Time: 6 or 24 h
Result: Showed no significant induction of early apoptosis at 6 h, while the evidence of extensive cell death of 56.2% occurred at later time (24 h), with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase 3 at 24-48 h.
体内実験

8α-Tigloyloxyhirsutinolide 13-O-acetate (5 mg/kg, Oral gavage, 5 times per week for 75 days) suppresses tumor growth in mice[1].

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

Animal Model: Five-week-old female athymic nude mice (injected subcutaneously in the right flank area with MDA-MB-468 cells in 100 μL PBS)
Dosage: 5 mg/kg
Administration: Oral gavage, every day, 5 times per week for 75 days
Result: Inhibited MDA-MB-468 xenografts growth in mice, with reduced pY705-STAT3, G6PD, TrxR1, and GSH levels.
分子量

420.45

分子式

C22H28O8

CAS 番号
Appearance

Solid

Color

White to off-white

SMILES

O=C(/C(C)=C/C)O[C@@H](C[C@H]1C)C(/C(OC2=O)=C\[C@](O[C@]13O)(CC3)C)=C2COC(C)=O

Structure Classification
Initial Source
輸送条件

Room temperature in continental US; may vary elsewhere.

保管条件

-20°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

純度とドキュメンテーション

純度: 95.0%

参考文献
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製品名:
8α-Tigloyloxyhirsutinolide 13-O-acetate
製品番号:
HY-138071
数量:
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