BCI ((E)-BCI) 是一种 DUSP6（双特异性磷酸酶 6）抑制剂。
货号:ajcx15114
CAS:1245792-51-1
分子式:C22H23NO
分子量：317.42
溶解度:DMSO: 125 mg/mL (393.80 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

BCI, as a selective dual-specificity phosphatase 6 (DUSP6) inhibitor, can inhibit tumor growth and macrophage inflammation.^[1].

In vitro, at low-dose of ≤2 μM and ≤4 μM, BCI showed no cytotoxic effects on RAW264.7 cells and BMMs, respectively. And at concentrations of ≤4 μM, BCI had no obvious effect on cell cycle progression or apoptosis in BMMs.^[1]In vitro experiment it shown that treatment with 1?μM BCI enhanced osteoclastogenesis by inhibiting DUSP6. Moreover, BCI increased the levels of osteoclast-related gene expression such as NFATC1, C-fos, ACP5, and DC-STAMP.^[2]In vitro efficacy test it demonstrated that treatment with 4?μm BCI obviously increased the proportion of cells expressing cleaved caspase‐3, 4?μm BCI already elicited extensive cytotoxicity in KELLY and IMR‐32 cells, and only a minority of LAN‐1 and SK‐N‐AS cells remained.^[3]In vitro, with 1 μM BCI did not affect total NCC and NCC surface expression as well as ERK1/2 phosphorylation. Treatment with 5 μM BCI can markedly increase ERK1/2 phosphorylation and decrease total NCC and NCC surface expression.^[5].

In vivo, mice were treated with 10mg/kg BCI intraperitoneally for five consecutive days per week, suppressed AKT activation and prevents tumor formation.^[4]In vivo test it exhibited that treatment with 50, 100, and 200 mg/kg BCI orally in the CPDM animal model obviously increased the number of pNrf2-positive cells in periodontal tissue and mitigated the alveolar bone loss.^[6].

参考文献:
[1] Cai C, et al. BCI Suppresses RANKL-Mediated Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss. Front Pharmacol. 2021 Nov 1;12:772540.
[2] Zhang B, et al. DUSP6 expression is associated with osteoporosis through the regulation of osteoclast differentiation via ERK2/Smad2 signaling. Cell Death Dis. 2021 Sep 2;12(9):825.
[3] Thompson EM, et al. The cytotoxic action of BCI is not dependent on its stated DUSP1 or DUSP6 targets in neuroblastoma cells. FEBS Open Bio. 2022 Jul;12(7):1388-1405.
[4] Duan S, et al. Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis. Cell Rep. 2021 Oct 19;37(3):109870.
[5] Feng X, et al. Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway. Am J Physiol Renal Physiol. 2015 May 15;308(10):F1119-27.
[6] Zhu C, et al. The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling pathway. J Periodontal Res. 2020 Jun;55(3):381-391.

Protocol:

Cell experiment [1]:
Cell lines	MPNST cells
Preparation Method	MPNST cells were starved overnight, incubated with BCI (2 uM) for 60 mins then stimulated with DMEM and 10% FBS for 1 hr. Immunoblot analysis of TP53, p-RB and p-ATM and PARP cleavage and CC3 in ST8814 and S462.TY MPNST cells 24h after treatment with BCI (2 uM).
Reaction Conditions	2 uM; 60 mins
Applications	After 1 hr, p-ERK, p-JNK, p-c-jun and total c-jun were elevated in the BCI-treated MPNST cell lines ST8814 and S462.TY but did not change in iHSC-1λ. Within 24 hours, BCI decreased total PARP and increased cleaved PARP and CC3, indicative of apoptotic cell death in NF1 deficient ST8814 and S462.TY cells.
Animal experiment [2]:
Animal models	Female C57BL/6 mice (8-weeks old)
Dosage form	15 mg/kg or 30 mg/kg; i.p.
Preparation method	Low- or high-concentration (15 mg/kg or 30 mg/kg) BCI was injected intraperitoneally for 8 weeks, and bone loss was evaluated by micro-CT.
Applications	Bone loss was prevented in both the low- and high-concentration BCI groups. Moreover, quantitative results indicated obvious increases in bone volume/total tissue volume (BV/TV), trabecular number (Tb.N), bone mineral density (BMD), and bone surface density (BS/TV) in both BCI-treated groups relative to the OVX group.
参考文献: [1] Ramkissoon A, et al. Targeted Inhibition of the Dual Specificity Phosphatases DUSP1 and DUSP6 Suppress MPNST Growth via JNK. Clin Cancer Res. 2019 Jul 1;25(13):4117-4127. [2] Cai C, et al. BCI Suppresses RANKL-Mediated Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss. Front Pharmacol. 2021 Nov 1;12:772540.