PIK-90 is a DNA-PK and PI3K inhibitor, which inhibits p110α, p110γ and DNA-PK with IC₅₀s of 11, 18 and 13 nM, respectively.

PIK-90 also inhibits p110β, p110δ, PI3KC2α, PI3KC2β, hsVPS34, PI4KIIIα, PI4KIIIβ, ATR, ATM and mTORC1 with IC₅₀s of 350 nM, 58 nM, 47 nM, 64 nM, 830 nM, 830 nM, 3.1 μM, 15 μM, 610 nM and 1.05 μM, respectively^[1]. To determine the effects of PIK-90 on chronic lymphocytic leukemia (CLL) cell viability, CLL cells from different patients are incubated with various concentrations of PIK-90 (1 μM and 10 μM) for 24, 48, and 72 hours. PIK-90 reveals the strong apoptosis-inducing effects at both concentrations and at all different time points. Using a concentration of 10 μM, PIK-90 reduces the viability of CLL cells to 51.1% plus or minus 6.6% at 24 hours, whereas 1 μM PIK-90 reduces the viability to 77.8% plus or minus 6.4%^[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.

To test the efficacy of Roscovitine and PIK-90 in vivo, GBM43 cells are implanted s.c. into nude mice. Mice with established tumors are randomized into four treatment groups: vehicle (PBS:H₂O), Roscovitine, PIK-90, or PIK-90 plus Roscovitine. After 12 d of treatment, both Roscovitine and PIK-90 show clear single-agent efficacy, with tumor size in mice treated with Roscovitine and PIK-90 in combination significantly smaller than either vehicle or monotherapy-treated controls. Roscovitine is less effective than PIK-90 in blocking proliferation (levels of Ki-67), whereas combination therapy shows essentially additive antiproliferative effects^[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.

351.36

C₁₈H₁₇N₅O₃

677338-12-4

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 : 6.67 mg/mL (18.98 mM; ultrasonic and adjust pH to 2 with HCl)

*

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。

In Vivo:

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: ≥ 0.67 mg/mL (1.91 mM); Clear solution

  此方案可获得 ≥ 0.67 mg/mL (1.91 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 6.7 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: ≥ 0.67 mg/mL (1.91 mM); Clear solution

  此方案可获得 ≥ 0.67 mg/mL (1.91 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 6.7 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: ≥ 0.67 mg/mL (1.91 mM); Clear solution

  此方案可获得 ≥ 0.67 mg/mL (1.91 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 6.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Knight ZA, et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.

  [2]. Niedermeier M, et al. Isoform-selective phosphoinositide 3′-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood. 2009 May 28;113(22):5549-57.

  [3]. Cheng CK, et al. Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12722-7.

To determine the viability of CLL B cells, 200 μL cells are removed from the wells of a 24-well plate at the indicated time points and incubated for 15 minutes in fluorescence-activated cell sorter buffer (RPMI+0.5% BSA) containing 40 nM 3,3′-dihexyloxacarbocyanine iodide (DiOC₆) and 10 μg/mL Propidium iodide (PI). Within 30 minutes, the cells are then analyzed by flow cytometry. Viable cells show high DiOC₆ and low PI fluorescence, whereas apoptotic cells have low DiOC₆ and PI fluorescence; necrotic cells are characterized by low DiOC₆ and high PI fluorescence. The normal PBMCs are also cultured under the same conditions, with or without the various PI3K inhibitors (e.g., PIK-90, 1 μM and 10 μM), Fludarabine, and with or without stromal cell support, and their viability is also determined by staining with DiOC₆ and PI^[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.

Mice^[3]
Human primary GBM43 cells (10⁶) are injected s.c. just caudal to the left forelimb in 4- to 6-wk-old female BALB/c nu/nu mice. After tumors are established (50-100 mm³), mice are randomly allocated to daily i.p. treatment with 40 mg/kg PIK-90 (DMSO:H₂O), 50 mg/kg Roscovitine (DMSO:PBS), 40 mg/kg PIK-90 plus 50 mg/kg Roscovitine, and DMSO:H₂O:PBS (control). Tumor diameters are measured with calipers at 3-d intervals, and volumes are calculated.

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]. Knight ZA, et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47.

  [2]. Niedermeier M, et al. Isoform-selective phosphoinositide 3′-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood. 2009 May 28;113(22):5549-57.

  [3]. Cheng CK, et al. Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12722-7.