GSK1838705A

SKU: orb1697923

Description

GSK1838705A is a potent, ATP-competitive small molecule inhibitor primarily targeting IGF-1R (IC50 2.0 nM), with additional activity against IR and ALK. It is a selective research tool used in vitro and in vivo to study signaling pathways in oncology, particularly in cancers driven by these receptors.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1116235-97-2
• MW: 532.57
• Purity: >99.99% (May vary between batches)
• Formula: C₂₇H₂₉FN₈O₃
• SMILES: CNC(=O)c1c(F)cccc1Nc1nc(Nc2cc3N(CCc3cc2OC)C(=O)CN(C)C)nc2[nH]ccc12
• Target: JNK,ALK,IGF-1R,S6 Kinase
• Solubility: DMSO:53.3 mg/mL (100.08 mM)

Bioactivity

• Target IC50:
  IGF-1R:2 nM|Insulin receptor:1.6 nM|ALK:0.5 nM
• In Vivo:
  GSK1838705A effectively inhibits the phosphorylation of IGF-1R (IC50: 85 nM) and IR (IC50: 79 nM) induced by ligands in cells. It demonstrates significant antiproliferative effects on various cell lines derived from solid and hematological tumors, such as L-82, SUP-M2, SK-ES, and MCF-7 (EC50: 24/28/141/203 nM). GSK1838705A induces the accumulation of MCF-7 and NCI-H929 cells in the G1 (2N) phase of the cell cycle. Additionally, it inhibits ALK (Ki: 0.35 nM) and the proliferation of cells expressing the NPM-ALK fusion protein (EC50: 24-88 nM). GSK1838705A significantly suppresses the phosphorylation of NPM-ALK in Karpas-299 and SR-786 cells, though it exhibits moderate effects on the phosphorylation of STAT3.
• In Vitro:
  In mice carrying COLO 205 tumors, GSK1838705A (30 mg/kg) inhibits 80% of tumor growth. Additionally, GSK1838705A demonstrates antitumor activity in mice with HT29 or BxPC3 xenografts. In mice with NIH-3T3/LISN tumors, GSK1838705A (60 mg/kg, p.o.) suppresses 77% of tumor growth without significant weight loss. It also momentarily doubles blood glucose levels by inhibiting IR signaling at a dose of 60 mg/kg. Furthermore, GSK1838705A (60 mg/kg) inhibits growth in established Karpas-299 xenografts by 93%, with no adverse effects on rat weight.
• Cell Research:
  Cells are seeded in 96-well dishes, incubated overnight at 37 °C, and treated with DMSO or GSK1838705A for 72 hours. For the NIH-3T3/LISN proliferation assays, cells are seeded on collagen-coated 96-well tissue culture plates and allowed to adhere for 24 hours. The medium is replaced with serum-free medium and the cells are treated with GSK1838705A for 2 hour. Cells are incubated for 72 hours 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 (XLfit4(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

JNK3, inhibit, IGF-1R, IGF1R, Inhibitor, Insulin Receptor, GSK1838705A, GSK-1838705A, Cluster of differentiation 246, CD246, Anaplastic lymphoma kinase (ALK), Anaplastic lymphoma kinase, ALK, ALK tyrosine kinase receptor, RSK1, S6Kinase, S6 Kinase

Compound Identifiers

PubChem CID

25182616