CPI-203 is a novel potent, selective and cell permeable inhibitor of BET bromodomain, with an IC₅₀ value of appr 37 nM (BRD4 α-screen assay).

IC50: 37 nM (BRD4)

CPI-203 inhibits BRD4 in vitro and in cells, but does not affect BRD4 kinase activity in vitro^[1]. CPI-203 exerts a cytostatic effect in all the 9 MCL cell lines analyzed with GI₅₀ ranging from 0.06 to 0.71 μM, with low cytotoxicity in normal PBMCs from healthy donors. Furthermore, CPI-203 efficiently activates the cell death program in MCL cells^[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.

CPI-203 (2.5 mg/kg, i.p.) combined with lenalidomide, enhances the antitumoral properties of each single agent via the abrogation of MYC and IRF4 expression and the induction of apoptosis in n REC-1 tumor-bearing mice^[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.

399.90

C₁₉H₁₈ClN₅OS

1446144-04-2

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 47 mg/mL (117.53 mM)

* “≥” means soluble, but saturation unknown.

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 (6.25 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.25 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% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (6.25 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.25 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 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: ≥ 2.5 mg/mL (6.25 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.25 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]. Devaiah BN, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32.

  [2]. Moros A, et al. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Oct;28(10):2049-59

CB17-severe combined immunodeficiency (SCID) mice are inoculated subcutaneously with 10⁷ cells of the indicated MCL cell line, and monitored for tumor growth and vital parameters as previously described. For lenalidomide and lenalidomide-bortezomib dosing, mice are randomly assigned into cohorts of 3-4 mice each and receive by intraperitoneal injection a twice weekly dose of bortezomib (0.15 mg/kg), a daily dose of lenalidomide (50 mg/kg), the combination of lenalidomide and bortezomib, or an equal volume of vehicle. In the lenalidomide-CPI-203 protocol, a total of 22 REC-1 tumor-bearing mice are randomly assigned to cohorts of 5-6 mice, receiving a twice daily intraperitoneal injection of 2.5 mg/kg CPI-203, a daily intraperitoneal injection of 50 mg/kg lenalidomide, both agents or an equal volume of vehicle. Between 26 and 29 days post-inoculation, animals are killed according to institutional guidelines and tumor samples are subjected to immunohistochemical staining using primary antibodies against phospho-histone H3, cleaved caspase-3 (5A1E) and MYC (D84C12), IRF4 (M-17) and platelet endothelial cell adhesion molecule-1 (PECAM-1) (M20), CD19 (LE-CD19), Blimp-1 (clone Ros195G/G5), PAX5 (clone 24), CCL3 and CD38, as previously described. Preparations are evaluated using an Olympus DP70 microscope and Cell B Basic Imaging Software.

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]. Devaiah BN, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32.

  [2]. Moros A, et al. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Oct;28(10):2049-59

CPI-203 is a novel potent, selective and cell permeable inhibitor of BET bromodomain, with an IC₅₀ value of appr 37 nM (BRD4 α-screen assay).

IC50: 37 nM (BRD4)

CPI-203 inhibits BRD4 in vitro and in cells, but does not affect BRD4 kinase activity in vitro^[1]. CPI-203 exerts a cytostatic effect in all the 9 MCL cell lines analyzed with GI₅₀ ranging from 0.06 to 0.71 μM, with low cytotoxicity in normal PBMCs from healthy donors. Furthermore, CPI-203 efficiently activates the cell death program in MCL cells^[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.

CPI-203 (2.5 mg/kg, i.p.) combined with lenalidomide, enhances the antitumoral properties of each single agent via the abrogation of MYC and IRF4 expression and the induction of apoptosis in n REC-1 tumor-bearing mice^[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.

399.90

C₁₉H₁₈ClN₅OS

1446144-04-2

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 47 mg/mL (117.53 mM)

* “≥” means soluble, but saturation unknown.

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 (6.25 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.25 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% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (6.25 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.25 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 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: ≥ 2.5 mg/mL (6.25 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.25 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]. Devaiah BN, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32.

  [2]. Moros A, et al. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Oct;28(10):2049-59

CB17-severe combined immunodeficiency (SCID) mice are inoculated subcutaneously with 10⁷ cells of the indicated MCL cell line, and monitored for tumor growth and vital parameters as previously described. For lenalidomide and lenalidomide-bortezomib dosing, mice are randomly assigned into cohorts of 3-4 mice each and receive by intraperitoneal injection a twice weekly dose of bortezomib (0.15 mg/kg), a daily dose of lenalidomide (50 mg/kg), the combination of lenalidomide and bortezomib, or an equal volume of vehicle. In the lenalidomide-CPI-203 protocol, a total of 22 REC-1 tumor-bearing mice are randomly assigned to cohorts of 5-6 mice, receiving a twice daily intraperitoneal injection of 2.5 mg/kg CPI-203, a daily intraperitoneal injection of 50 mg/kg lenalidomide, both agents or an equal volume of vehicle. Between 26 and 29 days post-inoculation, animals are killed according to institutional guidelines and tumor samples are subjected to immunohistochemical staining using primary antibodies against phospho-histone H3, cleaved caspase-3 (5A1E) and MYC (D84C12), IRF4 (M-17) and platelet endothelial cell adhesion molecule-1 (PECAM-1) (M20), CD19 (LE-CD19), Blimp-1 (clone Ros195G/G5), PAX5 (clone 24), CCL3 and CD38, as previously described. Preparations are evaluated using an Olympus DP70 microscope and Cell B Basic Imaging Software.

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]. Devaiah BN, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32.

  [2]. Moros A, et al. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Oct;28(10):2049-59

CPI-1612 is a highly potent, orally active EP300/CBP histone acetyltransferase (HAT) inhibitor with an IC₅₀ of 8.1 nM for EP300 HAT. CPI-1612 has an anticancer activity^[1].

IC50: 8.1 nM (EP300 HAT)^[1]

CPI-1612 inhibits full length EP300 and full length CBP with IC₅₀ values <0.5 nM and 2.9 nM, respectively^[1].
CPI-1612 inhibits H3K18Ac MSD (H3K18 = histone 3 lysine 18, MSD = meso scale discovery) and JEKO-1 cell proliferation with with IC₅₀ values 14 nM and <7.9 nM, respectively^[1].
CPI-1612 (compound 17) shows weak activity in a hERG binding assay (IC₅₀ = 10.4 μM) and displayed moderate inhibition of CYP2C8 (IC₅₀ = 1.9 μM) and CYP2C19 (IC₅₀ = 2.7 μM)^[1].

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.

CPI-1612 (compound 17; 0.5 mg/kg; oral administration; twice a day; for 4 weeks) treatment shows 67% tumor growth inhibition (TGI) with concomitant reduction of H3K27Ac in plasma and reduction of H3K18Ac in the tumor^[1].
While the oral exposure of CPI-1612 (compound 17) in dogs (0.5 mg/kg IV; 1.0 mg/kg PO; clearance = 0.42 L/h/kg, V_ss = 3.7 L/kg, T_1/2 = 5.5 h, F% = 71; AUC/dose = 1691 h·mg/mL) and mice (1 mg/kg IV; 5 mg/kg PO; clearance = 3.8 L/h/kg, V_ss = 2.0 L/kg, T_1/2 = 0.98 h, F% = 79; AUC/dose = 211 h·mg/mL) is good, the exposure in rats is limited by poor bioavailability (1.0 mg/kg IV; 5.0 mg/kg PO; clearance = 2.6 L/h/kg, V_ss = 1.8 L/kg, T_1/2 = 1.2 h, F% = 9; AUC/dose = 35.6 h·mg/mL)^[1].
A single dose of CPI-1612 is administered orally to CD-1 mice and brain and plasma exposures of CPI-1612 are measured at 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 h. CPI-1612 is highly brain-penetrant, showing a brain-to-plasma ratio of 0.35 after a single oral dose^[1].

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.

450.53

C₂₇H₂₆N₆O

2374971-81-8

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL (221.96 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: 5 mg/mL (11.10 mM); Suspended solution; Need ultrasonic

  此方案可获得 5 mg/mL (11.10 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 50.0 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: ≥ 5 mg/mL (11.10 mM); Clear solution

  此方案可获得 ≥ 5 mg/mL (11.10 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 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Jonathan E Wilson, et al. Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor. ACS Med Chem Lett. 2020 Apr 23;11(6):1324-1329.

CPI-455 is a specific, pan-KDM5 inhibitor with an IC₅₀ of 10 nM for KDM5A. CPI-455 mediates KDM5 inhibition, elevates global levels of H3K4me3, and decreases the number of drug-tolerant persister cancer cells in multiple cancer cell line models treated with standard chemotherapy or targeted agents^[1].

IC50: 10 nM (KDM5A)^[1]

CPI-455 mediates KDM5 inhibition, elevates global levels of H3K4 trimethylation (H3K4me3) and decreases the number of DTPs in multiple cancer cell line models treated with standard chemotherapy or targeted agents^[1].
CPI-455, with high measured affinity for the target KDM5 proteins. Within 24 hours, increases in H3K4me3, are observed after exposure to either of the two active compounds, CPI-455 and CPI-766, in a dosedependent manner. IC₅₀ calculation for KDM5 Inhibitor CPI0455 in 3 luminal breast cancer cell lines MCF-7, T-47 and EFM-19 are 35.4, 26.19 and 16.13 μM, respectively^[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.

Dual blockade of B7-H4 and KDM5B (CPI-455, 50/70 mg/kg, ip, daily) in mice elicits protective immunity^[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.

278.31

C₁₆H₁₄N₄O

1628208-23-0

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 34 mg/mL (122.17 mM)

* “≥” means soluble, but saturation unknown.

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。

• [1]. Vinogradova M, et al. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells. Nat Chem Biol. 2016 Jul;12(7):531-8.

  [2]. Benjamin R. Leadem. NOVEL HISTONE DEMETHYLASE INHIBITORS SYNERGISTICALLY

  [3]. Xiang Yuan, et al. Blockade of Immune-Checkpoint B7-H4 and Lysine Demethylase 5B in Esophageal Squamous Cell Carcinoma Confers Protective Immunity against P. gingivalis Infection. Cancer Immunol Res. 2019 Sep;7(9):1440-1456.