PFI-1 is a selective BET (bromodomain-containing protein) inhibitor for BRD4 with IC₅₀ of 0.22 μM in a cell-free assay.

IC50: 0.22 μM (BRD4)

PFI-1 has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G1 cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. Cells exposed to PFI-1 show significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, providing an alternative strategy for the specific inhibition of this well-established oncology target^[1]. PFI-1 binds to with cyclic AMP response binding protein with K_d of 49 μM. PFI-1 has an EC₅₀ of 1.89 μM for the inhibition of IL6 production from human blood mononuclear cells stimulated by LPS^[2]. PFI-1 induces dose-dependent reduction of cell viability in T4302 CD133⁺ cells^[3]. PFI-1 inhibits the proliferating of three NET cell lines (Bon-1 derived from a pancreatic NET, and H727 and H720 derived from lung NETs)^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

PFI-1 administrated (1 mg/kg, i.v.) in the rat results in the volume of distribution of 1 L/kg, the plasma clearance of 18 mL/min/kg and half-life of 1 hour. PFI-1 oral dosed (2 mg/kg) in the rat results in the oral bioavailability as low as 32%. PFI-1 administrated (2 mg/kg, s.c.) in the mouse results in a Cmax of 58 ng/mL with a Tmax of 1 h and a half-life of approximately 2 hours^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

347.39

C₁₆H₁₇N₃O₄S

1403764-72-6

Room temperature in continental US; may vary elsewhere.

DMSO : 33.33 mg/mL (95.94 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (7.20 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.20 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (7.20 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.20 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Picaud S, et al. PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains. Cancer Res. 2013 May 21. [Epub ahead of print]

  [2]. Fish PV, et al. Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem. 2012 Nov 26;55(22):9831-7.

  [3]. Cheng Z, et al. Inhibition of BET bromodomain targets genetically diverse glioblastoma. Clin Cancer Res. 2013 Apr 1;19(7):1748-59.

  [4]. Kate E Lines, et al. Epigenetic modifiers reduce proliferation of human neuroendocrine tumour cell lines. Endocrine Abstracts (2013) 31 P149

PFI-1 is a selective BET (bromodomain-containing protein) inhibitor for BRD4 with IC₅₀ of 0.22 μM in a cell-free assay.

IC50: 0.22 μM (BRD4)

PFI-1 has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G1 cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. Cells exposed to PFI-1 show significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, providing an alternative strategy for the specific inhibition of this well-established oncology target^[1]. PFI-1 binds to with cyclic AMP response binding protein with K_d of 49 μM. PFI-1 has an EC₅₀ of 1.89 μM for the inhibition of IL6 production from human blood mononuclear cells stimulated by LPS^[2]. PFI-1 induces dose-dependent reduction of cell viability in T4302 CD133⁺ cells^[3]. PFI-1 inhibits the proliferating of three NET cell lines (Bon-1 derived from a pancreatic NET, and H727 and H720 derived from lung NETs)^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

PFI-1 administrated (1 mg/kg, i.v.) in the rat results in the volume of distribution of 1 L/kg, the plasma clearance of 18 mL/min/kg and half-life of 1 hour. PFI-1 oral dosed (2 mg/kg) in the rat results in the oral bioavailability as low as 32%. PFI-1 administrated (2 mg/kg, s.c.) in the mouse results in a Cmax of 58 ng/mL with a Tmax of 1 h and a half-life of approximately 2 hours^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

347.39

C₁₆H₁₇N₃O₄S

1403764-72-6

Room temperature in continental US; may vary elsewhere.

DMSO : 33.33 mg/mL (95.94 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (7.20 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.20 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (7.20 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.20 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Picaud S, et al. PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains. Cancer Res. 2013 May 21. [Epub ahead of print]

  [2]. Fish PV, et al. Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem. 2012 Nov 26;55(22):9831-7.

  [3]. Cheng Z, et al. Inhibition of BET bromodomain targets genetically diverse glioblastoma. Clin Cancer Res. 2013 Apr 1;19(7):1748-59.

  [4]. Kate E Lines, et al. Epigenetic modifiers reduce proliferation of human neuroendocrine tumour cell lines. Endocrine Abstracts (2013) 31 P149

PFI-3 is a selective, potent and cell-permeable SMARCA2/4 bromodomain inhibitor with a K_d of 89 nM.

Kd: 89 nM (SMARCA2/4)^[1]

PFI-3 is a potent, cell-permeable probe capable of displacing ectopically expressed, GFP-tagged SMARCA2-bromodomain from chromatin. PFI-3 binds avidly to both SMARCA2 and SMARCA4 bromodomains (BROMOScan K_d‘s between 55 and 110 nM) consistent with the binding constant (K_d=89 nM) measured by isothermal titration calorimetry. PFI-3 does not phenocopy the growth inhibitory effects of SMARCA2 knockdown in lung cancer^[1]. Exposure of embryonic stem cells to PFI-3 leads to deprivation of stemness and deregulates lineage specification. Furthermore, differentiation of trophoblast stem cells in the presence of PFI-3 is markedly enhanced^[2]. PFI-3 binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII is achieved through a novel bromodomain binding mode of a phenolic headgroup that leads to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

321.37

C₁₉H₁₉N₃O₂

1819363-80-8

Room temperature in continental US; may vary elsewhere.

DMSO : 125 mg/mL (388.96 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.25 mg/mL (7.00 mM); Clear solution

  此方案可获得 ≥ 2.25 mg/mL (7.00 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 22.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.25 mg/mL (7.00 mM); Clear solution

  此方案可获得 ≥ 2.25 mg/mL (7.00 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 22.5 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.25 mg/mL (7.00 mM); Clear solution

  此方案可获得 ≥ 2.25 mg/mL (7.00 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 22.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Vangamudi B, et al. The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies. Cancer Res. 2015 Sep 15;75(18):3865-78.

  [2]. Fedorov O, et al. Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance. Sci Adv. 2015 Nov 13;1(10):e1500723.

  [3]. Gerstenberger BS, et al. Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit. J Med Chem. 2016 May 26;59(10):4800-11.

To establish whether PFI-3 intercalates DNA, the compound is assessed using a DNA unwinding assay. PFI-3 (1, 5, or 10 μM), cisplatin, or doxorubicin is incubated with supercoiled pBR322, in the presence of wheat germ topoisomerase I, for 30 min at 37°C. DNA incubated with DMSO in the presence or absence of the enzyme is run as control. After extraction by butanol and chloroform/isoamyl alcohol 24:1, the DNA is run in a 1% (w/v) agarose gel with a 1-kb DNA ladder for 4 hours at 80 V. The gel is then stained with SYBR Safe for 30 min before ultraviolet visualization^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Vangamudi B, et al. The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies. Cancer Res. 2015 Sep 15;75(18):3865-78.

  [2]. Fedorov O, et al. Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance. Sci Adv. 2015 Nov 13;1(10):e1500723.

  [3]. Gerstenberger BS, et al. Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit. J Med Chem. 2016 May 26;59(10):4800-11.