1. Protein Tyrosine Kinase/RTK
  2. ALK
    IGF-1R
    Insulin Receptor

GSK1838705A 

Cat. No.: HY-13020 Purity: 98.99%
Handling Instructions

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.

For research use only. We do not sell to patients.

GSK1838705A Chemical Structure

GSK1838705A Chemical Structure

CAS No. : 1116235-97-2

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 211 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
5 mg USD 180 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
10 mg USD 300 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 900 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 1140 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

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 & Target

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

In Vitro

In cellular phosphorylation assays, GSK1838705A potently inhibits IGF-IR and insulin receptor phosphorylation with IC50s of 85 and 79 nM, respectively. appKi 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].

In Vivo

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].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.8777 mL 9.3884 mL 18.7769 mL
5 mM 0.3755 mL 1.8777 mL 3.7554 mL
10 mM 0.1878 mL 0.9388 mL 1.8777 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[1]

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 appKi 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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

GSK1838705A is dissolved in DMSO at 10 mM for in vitro studies[1].

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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

GSK1838705A is formulated in 20% sulfobutyl ether β-cyclodextrin (ISP; pH 3.5)[1].

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] MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

532.57

Formula

C₂₇H₂₉FN₈O₃

CAS No.

1116235-97-2

SMILES

FC1=C(C(NC)=O)C(NC2=C3C(NC=C3)=NC(NC4=CC5=C(CCN5C(CN(C)C)=O)C=C4OC)=N2)=CC=C1

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

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
GSK1838705A
Cat. No.:
HY-13020
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