| Chemical Properties | Back Directory | [Boiling point ]
838.4±75.0 °C(Predicted) | [density ]
1.56±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
11.47±0.20(Predicted) | [color ]
Orange to reddish brown |
| Hazard Information | Back Directory | [Description]
F5446 is a SUV39H1 inhibitor. F5446 has an EC50 of 0.496 μmol/L for SUV39H1 enzymatic activity. H3K9me3 was enriched in the promoters of GZMB, PRF1, FASLG, and IFNG in quiescent T cells. F5446 inhibited H3K9me3, thereby upregulating expression of these effectors in tumor-infiltrating CTLs and suppressing colon carcinoma growth in a CD8+ CTL-dependent manner in vivo. Our data indicate that SUV39H1 represses CTL effector gene expression and, in doing so, confers colon cancer immune escape. | [Uses]
F5446 (Compound 1) is a selective small molecule inhibitor of SUV39H1 methyltransferase. F5446 decreases H3K9me3 deposition at the FAS promoter, increases Fas expression and increases colorectal carcinoma cell sensitivity to FasL-induced apoptosis in vitro. F5446 suppresses human colon tumor xenograft growth in vivo[1][2][3]. | [in vivo]
IF5446 (10 mg/kg, s.c.,every two days for 14 days) inhibits SUV39H1 and colon tumor growth at least in part through inhibiting H3K9me3 to increase the expression part through inhibiting H3K9me3 to increase the expression level of granzyme B , perforin , Fasl and IFNy in tumor-infiltrating CTLs in the tumor microenvironment in mice bearing MC38 and CT26 tumor[1][2].
IF5446 (10 and 20 mg/kg, s.c.,every two days for 14 days) increases T-cell effector expression to suppress colon carcinoma growth[3].
| Animal Model: | Mice bearing MC38 and CT26 tumor[1][2][3] | | Dosage: | 10 mg/kg | | Administration: | s.c.,every two days for 14 days | | Result: | Suppressed the tumor growth in a time-dependent manner and significantly increased the expression levels of granzymeB, perforin, FasL and IFNγ. |
| [References]
[1] Chunwan Lu, et al. Small molecule histone methyltransferase SUV39H1 inhibitor and uses thereof. US10577371B2. 2018.
[2] Lu C, et al. SUV39H1 regulates human colon carcinoma apoptosis and cell cycle to promote tumor growth. Cancer Lett. 2020 Apr 28;476:87-96. DOI:10.1016/j.canlet.2020.02.004
[3] Lu C, et al. SUV39H1 Represses the Expression of Cytotoxic T-Lymphocyte Effector Genes to Promote Colon Tumor Immune Evasion. Cancer Immunol Res. 2019 Mar;7(3):414-427. DOI:10.1158/2326-6066.CIR-18-0126 |
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| Company Name: |
cjbscvictory
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| Tel: |
13348960310 |
| Website: |
https://www.weikeqi-biotech.com/ |
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