PF-2771 is a potent and selective centromere protein E (CENP-E) inhibitor, inhibiting CENP-E motor activity with an IC₅₀ of 16.1 nM; PF-2771 is used as an anticancer agent.

PF-2771 is a potent and selective CENP-E inhibitor, inhibiting CENP-E motor activity with an IC₅₀ of 16.1 nM. PF-2771 shows no inhibitory effect on the ATPase activities of highly related kinesins (0% inhibition of Eg5/KSP, chromokinesin, and MCAK at both 1 or 10 μM PF-2771). PF-2771 exhibits inactive activity against 74 protein kinases (all < 23% inhibition with 1 μM PF-2771, < 40% with 10 μM PF-2771). PF-2771 is cytotoxic to the basal-like breast cancer tumor cell survival, with EC₅₀s of < 0.1 μM, and with no cytotoxicity on the normal and premalignant cell lines (EC₅₀ > 5 μM). PF-2771 (100 nM) reusults in a chromosomal congression defect in MDA-MB-468 cells^[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.

PF-2771 (100 mg/kg, every day i.p.) potently inhibits CENP-E motor function, and causes tumor regression in SCID mice bearing AA1077 mammary tumors^[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.

554.08

C₂₉H₃₆ClN₅O₄

2070009-55-9

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 32 mg/mL (57.75 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]. Kung PP, et al. Chemogenetic evaluation of the mitotic kinesin CENP-E reveals a critical role in triple-negative breast cancer. Mol Cancer Ther. 2014 Aug;13(8):2104-15.

Microtubule-activated CENP-E kinesin ATPase activity is measured spectrophotometrically by coupling the hydrolysis of ATP to ADP to NADH oxidation (decrease in 340 nm absorbance) through the activities of pyruvate kinase (PK) and lactate dehydrogenase (LDH). Reactions contained 2 mM phosphoenolpyruvate, 0.28 mM NADH, 5 mM MgCl₂, 1 mM DTT, 15 μM taxol, 0.7 μM MT (preformed porcine microtubules), 50 μM ATP, 10 U/mL PK, and 10 U/mL LDH in 15 mM PIPES buffer (pH 7.0). Reactions are initiated with a 20 nM CENP-E addition (Human: 1-342; WT) at 30°C. The IC₅₀ values are determined by a nonlinear, least squares fit of the data to the four-parameter dose-response curve equation. PF-2771 kinesin biochemical selectivity toward other kinesins is tested in triplicate at both 1 and 10 μM PF-2771 in a variant of the CENP-E enzymatic assays that have the following enzyme concentrations: 200 nM chromokinesin motor domain, 200 nM Eg5 motor domain, 226 nM MCAK motor domain. PF-2771 biochemical mechanism is determined by measuring CENP-E enzymatic activity as a function of ATP and PF-2771 concentrations (0, 2.5, 5, 10, 20, 30, 45 nM PF-2771; 1,000, 500, 250, 125, 62.5, 31.2, 15.6, 7.81, 3.90, 1.95, 0.977 μM ATP)^[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.

PF-2771 is added to cells seeded in 96-well plates. The number of cells seeded (1,000-3,000) depended on growth characteristics of each cell type and normalized proliferation rates. Ten different concentrations of compound (PF-2771) used are based on a half-log increment between 1 nM and either 1 or 25 μM. Cells are incubated at 37°C for 7 days before assessing viability with the CellTiter-Glo reagent. Untreated control cells are 80% to 90% confluent after 7 days of culture. Data are fitted into a sigmoidal curve-fitting program to calculate IC₅₀ values^[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.

HCC1806 tumor cells (3 × 10⁶) are implanted in the mammary fat pad of CB17/lcr.Cg-PrkdcscidLystbg female mice. PF-2771 is administered intraperitoneally (i.p.) to groups of 12 mice at 3, 10, and 30 mg/kg every day for 14 days and at 100 mg/kg every day for 4 days followed by 3 days off and then another 4-day cycle. Tumor volumes are recorded twice weekly by calipers with the final measurement taken 3 days after the last dose. Tumor growth inhibition (TGI) is calculated using the formula 100 × (1 − ΔT/ΔC), where ΔT (treated) and ΔC (control) are the mean tumor volume changes between 1 day after the last dose and the first-day treatment. Time-to-progression endpoint and associated tumor growth delay determinations are calculated using median days to reach to two doublings of initial tumor size. Statistical comparisons are made using one-way ANOVA with Dunnett posttests. Other tumor models had similar methodology except where noted. PDX-AA1077 is a patient-derived xenograft model developed from tumor tissue from a triple-negative patient engrafted to the mammary glands of NSG female mice to create passage 1 tumor-bearing mice. Surgically resected tumor tissue is cut into 2- to 4-mm³ fragments and subcutaneously implanted into the flank of SCID-bg mice. Mice with palpable tumors are randomized before dosing. An HCC1599 tumor cell line xenograft model is established from tumor fragments of established tumors and reimplanted into flank of female SCID mice. When average tumor size reached 250 mm³, animals are randomized into five groups of 10 mice. Animals are treated with vehicle (daily dosing), 10 mg/kg docetaxel (once per week dosing), 25 mg/kg docetaxel (once per week dosing), 20 mg/kg paclitaxel (twice per week dosing), or 100 mg/kg of PF-2771 (every day, i.p.)^[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.

• [1]. Kung PP, et al. Chemogenetic evaluation of the mitotic kinesin CENP-E reveals a critical role in triple-negative breast cancer. Mol Cancer Ther. 2014 Aug;13(8):2104-15.