FX1

製品コードS8591 バッチS859102

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C14H9ClN2O4S2
分子量 368.82 CAS No. 1426138-42-2
Solubility (25°C)* 体外 DMSO 37 mg/mL (100.31 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
0.9mg/ml Taking the 1 mL working solution as an example, add 50 μL of 18 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
0.3mg/ml Taking the 1 mL working solution as an example, add 50 μL of 6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 FX1 is a selective BCL6 BTB inhibitor with an IC50 value of 35 μM in reporter assays. FX1 shows great selectivity against a panel of 50 different kinases. 10 μM FX1 fails to significantly inhibit of any of these kinases. FX1 induces apoptosis.
in vitro

FX1 disrupted formation of the BCL6 repression complex, reactivated BCL6 target genes, and mimicked the phenotype of mice engineered to express BCL6 with corepressor binding site mutations. FX1 suppressed ABC-DLBCL cells in vitro and in vivo, as well as primary human ABC-DLBCL specimens ex vivo. FX1 is specific to BCL6 and binds with a greater affinity than the natural BCL6 ligand SMRT. FX1 almost invariantly induced significant derepression of these genes(BCL6 target genes CASP8, CD69, CXCR4, CDKN1A, and DUSP5) as compared with vehicle in 2 independent DLBCL cell lines. FX1 was more than 100-fold more powerful than the previous generation of BCL6 inhibitors represented by 79-6, and 300-fold more potent than the recently reported binding of the antibiotics rifamycin and rifabutin (KD ~1 mM)[1].
in vivo

Low doses of FX1 induce regression of established tumors in mice bearing DLBCL xenografts. The half-life is estimated to be approximately 12 hours for FX1 in SCID mice. No signs of toxicity, inflammation, or infection are evident from H&E-stained sections of lung, gastrointestinal tract, heart, kidney, liver, spleen, and bone marrow of the fixed organs from mice treated with FX1 compared with vehicle. Peripheral blood counts and serum chemistry in FX1-treated mice are also examined and they remain within normal parameters. FX1 causes profound and significant suppression of DLBCLs in DLBCL xenografts, and indeed not only prevented growth of the xenografts but in addition causes these tumors to shrink from their initial volume. The maximal effect is already achieved by the lower 25 mg/kg dose. TUNEL and Ki-67 staining shows that FX1 also induced more apoptosis and growth arrest than 79-6, respectively[1].
特徴 Recommend for freshly prepared each time for in vitro experiment

プロトコル(参考用のみ)

細胞アッセイ 細胞株 DLBCL cells, SUDHL-6 cells
濃度 50 μM
反応時間 30 min
実験の流れ

Quantitative ChIP is performed in SUDHL-6 cells exposed to FX1 (black bars) or vehicle (white bars) in DLBCL cells using antibodies for BCL6, SMRT, BCOR, or IgG control to enrich for known BCL6 binding sites in the CD69, CXCR4, and DUSP5 loci, or a negative control region.
動物実験 動物モデル SCID mice bearing SUDHL-6 xenografts
投薬量 50 mg/kg
投与方法 i.p.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

BCL6 is a context-dependent mediator of the glioblastoma therapy response [ Victoria University of Wellington, 2023, ] PubMed: none
BCL6 inhibition ameliorates ruxolitinib resistance in CRLF2-rearranged acute lymphoblastic leukemia [ Haematologica, 2022, 10.3324/haematol.2022.280879] PubMed: 36005560
The Cdkn2a gene product p19 alternative reading frame (p19ARF) is a critical regulator of IFNβ-mediated Lyme arthritis [ PLoS Pathog, 2022, 18(3):e1010365] PubMed: 35324997
Dynamic regulation of B cell complement signaling is integral to germinal center responses [ Nat Immunol, 2021, 22(6):757-768] PubMed: 34031614
Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma [ Blood Adv, 2021, bloodadvances.2021005682] PubMed: 34625792
FX1, a BCL6 inhibitor, reactivates BCL6 target genes and suppresses HTLV-1-infected T cells [ Invest New Drugs, 2021, 10.1007/s10637-021-01196-1] PubMed: 34698964
Immediate adaptation analysis implicates BCL6 as an EGFR-TKI combination therapy target in NSCLC. [ Mol Cell Proteomics, 2020, 31 pii: mcp] PubMed: 32234966
BCL6 inhibitor FX1 attenuates inflammatory responses in murine sepsis through strengthening BCL6 binding affinity to downstream target gene promoters. [ Int Immunopharmacol, 2019, 75:105789] PubMed: 31401377
[ Oncotarget, 2018, ] PubMed: 30323893

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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