GSK1838705A is a potent and reversible IGF-IR and the insulin receptor inhibitor with IC₅₀s of 2.0 and 1.6 nM, respectively. It also inhibits ALK with an IC₅₀ of 0.5 nM.

IC50: 2.0 nM (IGF-IR), 1.6 nM (insulin receptor), 0.5 nM (ALK)^[1]

In cellular phosphorylation assays, GSK1838705A potently inhibits IGF-IR and insulin receptor phosphorylation with IC₅₀s of 85 and 79 nM, respectively. ^appK_i values are 0.7 nM for IGF-IR and 1.1 nM for insulin receptor using the filter binding assay. GSK1838705A inhibits the proliferation in a panel of cell lines derived from solid and hematologic tumors. The EC₅₀s of GSK1838705A range from 20 nM to >8 μM, but are <1 μm in most multiple myeloma and ewing's sarcoma cell lines^[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.

GSK1838705A shows robust antitumor activity in animal xenograft models. Tumor types likely to respond to GSK1838705A include multiple myeloma and Ewing’s sarcoma, as well as ALK-driven tumors (e.g., ALCL, NSCLC, and neuroblastoma). A single oral dose of GSK1838705A at 0.1 and 0.3 mg/kg results in 35% and 65% inhibition of IGF-IR phosphorylation, respectively, whereas doses ≥1 mg/kg results in complete inhibition of ligand-induced IGF-IR phosphorylation^[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.

532.57

C₂₇H₂₉FN₈O₃

1116235-97-2

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 : ≥ 100 mg/mL (187.77 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。

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: 3 mg/mL (5.63 mM); Suspended solution; Need ultrasonic

  此方案可获得 3 mg/mL (5.63 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 30.0 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

• [1]. Sabbatini P, et al. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20.

Baculovirus-expressed glutathione S-transferase–tagged proteins encoding the intracellular domain of IGF-IR (amino acids 957–1367) and IR (amino acids 979–1382) are used for determinations of IC₅₀s by a homogeneous time-resolved fluorescence assay. A filter binding assay is used for ^appK_i determinations using activated IGF-IR and IR kinases. Expanded kinase-selectivity profiling of GSK1838705A is carried out by screening the compound in the KinaseProfiler panel^[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.

Cells are seeded in 96-well dishes, incubated overnight at 37°C, and treated with DMSO or GSK1838705A for 72 h. For the NIH-3T3/LISN proliferation assays, cells are seeded on collagen-coated 96-well tissue culture plates and allowed to adhere for 24 h. The medium is replaced with serum-free medium and the cells are treated with GSK1838705A for 2 h. Cells are incubated for 72 h after addition of IGF-I (30 ng/mL). Cell proliferation is quantified using the CellTiter-Glo Luminescent Cell Viability Assay. IC₅₀s are determined from cytotoxicity curves using a four-parameter curve fit software package^[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.

Mice: Exponentially growing cells are implanted s.c. into the right flank of 8- to 12-wk-old female nu/nu CD-1 or SCID mice. Mice are dosed p.o. with the formulating vehicle or GSK1838705A. Mice are weighed and tumors measured by calipers twice weekly. Tumor volumes are calculated^[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]. Sabbatini P, et al. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20.