PQR620 is an orally bioavailable and selective brain penetrant inhibitor ofmTORC1/2^[1].

PQR620 is a potent and selective mTOR inhibitor, which induces >1000-fold selectivity towards mTOR over PI3Kα in enzymatic binding assays. In A2058 melanoma cells PQR620 demonstrates inhibition of protein kinase B (pSer473) and ribosomal protein S6 (pSer235/236) phosphorylation with IC₅₀values of 0.2 μM and 0.1 μM, respectively. PQR620 shows excellent selectivity over a wide panel of kinases, as well as excellent selectivity versus unrelated receptor enzymes and ion channels. PQR620 demonstrates its potency to prevent cancer cell growth in an NTRC 44 cancer cell line panel, resulting in a¹⁰log(IC₅₀) of 2.86 (nM)^[1]. PQR620 has a median IC₅₀of 250 nM when tested on 44 lymphoma cell lines. Activity is higher in B cell than in T cell tumors (median IC₅₀s: 250 nM vs 450 nM; P=0.002). At 72h, anti-tumor activityof PQR620 is mostly cytostatic and apoptosis induction is seen only in 6/44 cell lines (13%). Sensitivity to PQR620 or apoptosis induction does not differ between DLBCL and MCL, and they are not affected by the DLBCL cell of origin, byTP53status or by the presence ofMYCorBCL2translocations^[2].

The physico-chemical properties of PQR620 result in good oral bioavailability and excellent brain penetration^[1]. The activity of PQR620 as single agent undergoes in vivo evaluation in two DLBCL models, the germinal center B cell type DLBCL (GCB-DLBCL) SU-DHL-6 and the acivated B cell-like DLBCL (ABC-DLBCL) RIVA. Treatments with PQR620 (100 mg/kg dose per day, Qd×7/w) start with 100-150 mm³tumors and are carried for 14 (SU-DHL-6) or 21 days (RIVA). In both models, PQR620 determines a 2-fold decrease of the tumor volumes in comparison with control, with significant differences in both SU-DHL-6 (D7, D9, D11, D14; P<0.005) and RIVA (D14, D16, D19, D21; P<0.005)^[2].

445.47

Solid

C₂₁H₂₅F₂N₇O₂

1927857-56-4

Room temperature in continental US; may vary elsewhere.

DMSO : 6.4 mg/mL(14.37 mM;Need warming)

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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 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: ≥ 2.08 mg/mL (4.67 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.67 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 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-CDin saline)

  Solubility: ≥ 2.08 mg/mL (4.67 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.67 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 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: ≥ 2.08 mg/mL (4.67 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.67 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。