Palbociclib isethionate is a highly selective inhibitor of CDK4/6 with IC₅₀s of 11 nM/16 nM, respectively.

Palbociclib exhibits absolute selectivity for CDK4/6 with little or no activity against other CDKs. Palbociclib is effective at reducing Rb phosphorylation at Ser⁷⁸⁰ and Ser⁷⁹⁵ in MDA-MB-435 breast carcinoma cells with IC₅₀ of 66 nM and 63 nM, respectively. Palbociclib is a potent inhibitor of cell growth and suppresses DNA replication by preventing cells from entering S phase. Palbociclib inhibits thymidine incorporation into the DNA of Rb-positive human breast (such as MDA-MB-435, MCF-7), colon (H1299), and lung carcinomas (Colo-205) as well as human leukemias (CRRF-CEM and K562), with IC₅₀ values ranging from 0.04-0.17 μM. Palbociclib significant increases the percentage of MDA-MB-453 in G1 period^[1]. Palbociclib inhibits phosphorylation of Rb in cycling CD138+ primary bone marrow myeloma cells, nontransformed primary B cells, MM1.S and CAG HMCLs cells line with IC₅₀ of <0.1 μM, 0.05 μM, and 60-70 nM, respectively. Palbociclib treatment also induces G1 arrest of CD138+ primary bone marrow myeloma and nontransformed primary B cells. Palbociclib induces G1 arrest in MM1.S with IC₅₀ of appr 0.05 μM^[2]. Palbociclib preferentially inhibits proliferation of luminal estrogen receptor-positive (including HER2-positive) human breast cancer cell lines. Palbociclib increases gene expression of pRb and cyclin D1 and decreases gene expression of CDKN2A (p16) in most sensitive lines. Palbociclib enhances sensitivity to ICI 47699 in cell lines with conditioned resistance to ER blockade^[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.

Palbociclib(150 mg/kg. p.o.) produces rapid Colo-205 colon carcinoma xenografts regressions and a corresponding tumor growth delay. Palbociclib (150 mg/kg, p.o.) induces complete tumor stasis and cell kill in MDA-MB-435 breast carcinoma. Palbociclib (150 mg/kg) also induces significant tumor regression in mice bearing the SF-295 glioblastoma xenografts, and in ZR-75-1 breast and PC-3 prostate tumor models (complete suppression of tumor growth). Palbociclib (150 mg/kg) suppresses Rb Ser⁷⁸⁰ phosphorylation in MDA-MB-435 breast carcinoma over the full 24-hour period. Palbociclib (150 mg/kg) down-regulates expression of four E2F-regulated genes CDC2, CCNE2, TK1, and TOP2A in Colo-205 carcinoma xenografts^[1]. Palbociclib also rapidly inhibits myeloma tumor growth^[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.

573.66

C₂₆H₃₅N₇O₆S

827022-33-3

帕博西尼羟乙基磺酸盐；帕博西丽羟乙基磺酸盐；帕布西利布羟基乙磺酸盐；帕布昔利布羟乙基磺酸盐；帕波西比羟乙基磺酸盐

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

H₂O : 50 mg/mL (87.16 mM; Need ultrasonic)

DMSO : 10 mg/mL (17.43 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 (sealed storage, away from moisture)。-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    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 1 mg/mL (1.74 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (1.74 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 10.0 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

• [1]. Fry DW, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther, 2004, 3(11), 1427-1438.

  [2]. Baughn LB, et al. A novel orally active small molecule potently induces G1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6. Cancer Res. 2006 Aug 1;66(15):7661-7.

  [3]. Finn RS, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77.

Cells are seeded in duplicate at 5,000 to 10,000 cells per well in 24-well plates. The day after plating, different concentrations of Palbociclib are added. Control wells without drug are also seeded. At the end of incubation, cells are trypsinizated and placed in Isotone solution and counted immediately using a Coulter Z2 particle counter.

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.

Mice (18-22 g) are randomized and then implanted s.c. with tumor fragments (appr 30 mg) into the region of the right axilla. Treatment is initiated when tumors reach 100 to 150 mg. Palbociclib is given according to the schedule and dose indicated in the table and figure legends by gavage as a solution in sodium lactate buffer (50 mM, pH 4.0) based on mean group body weight. In all experiments, there are 12 mice in the control group and 8 mice each in the treated groups. Additional details for each experiment are given in the table legends.

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]. Fry DW, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther, 2004, 3(11), 1427-1438.

  [2]. Baughn LB, et al. A novel orally active small molecule potently induces G1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6. Cancer Res. 2006 Aug 1;66(15):7661-7.

  [3]. Finn RS, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77.