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HazMat fee for 500 gram (Estimated)
Excepted Quantity
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Inaccessible (Haz class 6.1), International
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Accessible (Haz class 3, 4, 5 or 8), International
HO-3867, a curcumin analogue, is a selective STAT3 inhibitor. It selectively inhibited STAT3 phosphorylation, transcription, and DNA binding without affecting the expression of other active STATs at 10μM. HO-3867 significantly inhibited BRCA-mutated ovarian cancer cells expressing higher level of Tyrosine-phosphorylated STAT3 (pTyr705) in vitro, in a dose (1-20μM)- and time (12-48h)-dependent manner, with apoptosis shown by elevated levels of cleaved caspase-3, caspase-7 and PARP. Also, treatment with HO-3867 resulted in decreased expression of pTyr705 and its downstream targets cyclin D1, Bcl-2 and surviving in these cells. HO-3867 is a safe STAT3 Inhibitor for it exhibited minimal toxicity toward noncancerous cells and tissues but induced apoptosis in ovarian cancer cells. It inhibited cell migration/invasion and survival of primary human ovarian cancer cells isolated from patient ascites at 10μM post 24h. Administration of HO-3867 at 100ppm could block xenograft tumor growth without toxic side effects in nude mice injected with A2780 cells.
作用机制
HO-3867 has high affinity for a pocket located on the DNA-binding domain of the STAT3 and it could interact with both the STAT3 dimer and monomer structures.[1]
HO-3867 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CHO cells
10 µM
24 hours
HO-3867 exhibited minimal toxicity toward normal cells
Cancer Res. 2014 Apr 15;74(8):2316-27.
Ishikawa (IK) cells
5 µM
24 hours
Inhibition of EV secretion and EC cell proliferation
Oncogene. 2024 Nov;43(49):3586-3597.
Leishmania donovani promastigotes
1-200 µg/ml
2 hours
HO-3867 induced oxidative stress-mediated apoptosis in L. donovani promastigotes, characterized by altered cell morphology, phosphatidylserine externalization, mitochondrial depolarization, intracellular lipid accumulation, and cell cycle arrest.
Front Cell Infect Microbiol. 2021 Dec 3;11:774899.
Leishmania major promastigotes
1-200 µg/ml
2 hours
HO-3867 induced dose-dependent apoptosis in L. major promastigotes.
Front Cell Infect Microbiol. 2021 Dec 3;11:774899.
A2780 human epithelial ovarian cancer cells
10 µM
24 hours
To evaluate the inhibitory effect of HO-3867 on the STAT3 signaling pathway and its impact on cancer cell apoptosis. Results showed that HO-3867 significantly reduced the phosphorylation levels of STAT3 and induced apoptosis in cancer cells.
Free Radic Biol Med. 2010 May 1;48(9):1228-35.
HSMC human aortic smooth muscle cells
10 µM
24 hours
To evaluate the effect of HO-3867 on the viability of noncancerous cells. Results showed that HO-3867 was significantly less toxic to HSMC cells compared to cancer cells.
Free Radic Biol Med. 2010 May 1;48(9):1228-35.
OVTOKO cells
5 µM and 10 µM
24 hours
Treatment with HO-3867 decreased expression of pSTAT3 Tyr705 as well pSTAT3 Ser727, while total STAT3 remained constant.
Int J Cancer. 2017 Nov 1;141(9):1856-1866.
JHOC cells
5 µM and 10 µM
24 hours
Treatment with HO-3867 decreased expression of pSTAT3 Tyr705 as well pSTAT3 Ser727, while total STAT3 remained constant.
Int J Cancer. 2017 Nov 1;141(9):1856-1866.
A2780 cells
10 µM
24 hours
HO-3867 induced G2/M cell-cycle arrest in A2780 cells by modulating cell-cycle regulatory molecules p53, p21, p27, cdk2 and cyclin, and promoted apoptosis by caspase-8 and caspase-3 activation.
Mol Cancer Ther. 2010 May;9(5):1169-79.
SKOV3 cells
10 µM
24 hours
HO-3867 significantly inhibited the proliferation of SKOV3 cells and induced apoptosis.
Mol Cancer Ther. 2010 May;9(5):1169-79.
OVCAR3 cells
10 µM
24 hours
HO-3867 significantly inhibited the proliferation of OVCAR3 cells and induced apoptosis.
Mol Cancer Ther. 2010 May;9(5):1169-79.
U2OS cells
2, 4, 8, 16, 32 µM
24 hours
HO-3867 significantly reduced the viability of U2OS cells and induced apoptosis
Pharmaceutics. 2022 Jun 13;14(6):1257.
HOS cells
2, 4, 8, 16, 32 µM
24 hours
HO-3867 significantly reduced the viability of HOS cells and induced apoptosis
Pharmaceutics. 2022 Jun 13;14(6):1257.
MG-63 cells
2, 4, 8, 16, 32 µM
24 hours
HO-3867 significantly reduced the viability of MG-63 cells and induced apoptosis
Pharmaceutics. 2022 Jun 13;14(6):1257.
Ishikawa cells
5 and 10 µM
24 hours
HO-3867 significantly decreased the expression of pSTAT3 Ser727 while total STAT3 remained constant; cell viability decreased by 50–80% and induced G2/M arrest in 55% of Ishikawa cells at the G2/M cell cycle checkpoint.
Gynecol Oncol. 2014 Oct;135(1):133-41.
Human oral squamous cell carcinoma SCC-9 cells
0, 2.5, 5, 10, and 20 µM
24 hours
To evaluate the effect of HO-3867 on SCC-9 cell growth, results showed that HO-3867 effectively suppressed SCC-9 cell growth.
J Cell Mol Med. 2022 Apr;26(8):2273-2284.
Human oral squamous cell carcinoma HSC-3 cells
0, 2.5, 5, 10, and 20 µM
24 hours
To evaluate the effect of HO-3867 on HSC-3 cell growth, results showed that HO-3867 effectively suppressed HSC-3 cell growth.
J Cell Mol Med. 2022 Apr;26(8):2273-2284.
A195 cells
10 µM
24-72 hours
HO-3867 significantly suppressed the survival of A195 cells
Oncogene. 2017 Jan 12;36(2):168-181.
Ishikawa cells
5 and 10 µM
3 and 6 hours
HO-3867 selectively induced G2/M cell-cycle arrest in Ishikawa cells in a dose and time-dependent manner, with the greatest increase in G2/M cell population at 6 hours.
Gynecol Oncol. 2014 Oct;135(1):133-41.
A2780 cells
10 µM
3 hours
HO-3867 inhibited STAT3 nuclear translocation
Cancer Res. 2014 Apr 15;74(8):2316-27.
Human pulmonary artery smooth muscle cells
0.5 µM and 1 µM
48 and 72 hours
To study the effect of HO-3867 on peroxynitrite-induced cell proliferation, results showed that HO-3867 is capable of scavenging peroxynitrite and inhibiting peroxynitrite-induced smooth muscle cell proliferation.
Hypertension. 2013 Mar;61(3):593-601.
HUVEC cells
5 µM and 10 µM
HO-3867 significantly inhibited formation of capillary-like structures and invasion in HUVEC cells.
Int J Cancer. 2017 Nov 1;141(9):1856-1866.
Murine macrophages
100 µg/ml
HO-3867 was completely safe for normal murine macrophages.
Front Cell Infect Microbiol. 2021 Dec 3;11:774899.
HO-3867 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Left-heart failure-induced pulmonary hypertension model
Dietary administration
100 ppm
Continued for 4 weeks
To study the effect of HO-3867 on left-heart failure-induced pulmonary hypertension, results showed that HO-3867 significantly attenuated the increase in pulmonary artery pressure and inhibited vascular remodeling by restoring PTEN activity.
Hypertension. 2013 Mar;61(3):593-601.
C57BL/6 mice
High-fat diet-induced endometrial hyperplasia model
Oral
2 mg/kg
8 weeks
Inhibition of high-fat diet-induced endometrial hyperplasia and EV secretion
Oncogene. 2024 Nov;43(49):3586-3597.
BALB/c Nude mice
Ovarian cancer xenograft model
Oral
25, 50, 100 ppm
Once daily for 35 days
HO-3867 significantly inhibited the growth of the ovarian xenografted tumors in a dosage-dependent manner without any apparent toxicity.
Mol Cancer Ther. 2010 May;9(5):1169-79.
BALB/c Nude mice
Endometrial cancer xenograft model
Oral
50 and 100 ppm
Continuous for 4 weeks
HO-3867 significantly inhibited the growth of xenograft endometrial tumors and induced apoptosis in vivo.
Gynecol Oncol. 2014 Oct;135(1):133-41.
Mice
Orthotopic ovarian cancer model
Oral
50 and 100ppm
Once daily for 6 weeks
HO-3867 significantly suppressed ovarian tumor growth, angiogenesis, and metastasis
Oncogene. 2017 Jan 12;36(2):168-181.
Nude mice
A2780cDDP xenograft model
Oral
50 or 100 ppm
28 days
HO-3867 significantly inhibited tumor growth without toxic side effects
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