research use only

GSK1904529A IGF-1R inhibitor

Name: GSK1904529A
Brand: Selleck Chemicals
SKU: S1093
Availability: InStock
Rating: 5 (26 reviews)

Cat.No.S1093

GSK1904529A (GSK 4529) is a selective inhibitor of IGF-1R and IR with IC50 of 27 nM and 25 nM in cell-free assays, >100-fold more selective for IGF-1R/InsR than Akt1/2, Aurora A/B,B-Raf, CDK2, EGFR etc.

Chemical Structure

Molecular Weight: 851.96

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.98%

99.98

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src FLT3 HER2 c-Kit Bcr-Abl MEK BTK ALK Trk receptor Syk Axl CSF-1R c-RET FAK Mertk Tie-2 DYRK Tyro3 Ephrin receptor ROS1 Pyk2 RON DDR ACK Fer kinase
Related Products	Linsitinib (OSI-906) NVP-AEW541 BMS-754807 Picropodophyllin (PPP) BMS-536924 AG-1024 NVP-ADW742 NT157 PQ 401

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description
NIH3T3 cells	Function assay		Inhibition of human insulin receptor autophosphorylation in transfected mouse NIH3T3 cells, IC50=19 nM
human TC71 cells	Proliferation assay	72 h	Antiproliferative activity against human TC71 cells after 72 hrs by Celltiter assay, IC50=35 nM
human SK-ES cells	Proliferation assay	72 h	Antiproliferative activity against human SK-ES cells after 72 hrs by Celltiter assay, IC50=61 nM
human NCI-H929 cells	Proliferation assay	72 h	Antiproliferative activity against human NCI-H929 cells after 72 hrs by Celltiter assay, IC50=81 nM
human LP-1 cells	Proliferation assay	72 h	Antiproliferative activity against human LP-1 cells after 72 hrs by Celltiter assay, IC50=104 nM
human COLO205 cells	Proliferation assay	72 h	Antiproliferative activity against human COLO205 cells after 72 hrs by Celltiter assay, IC50=124 nM
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	851.96	Formula	C₄₄H₄₇F₂N₉O₅S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1089283-49-7	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	GSK 4529			Smiles	CCC1=CC(=C(C=C1N2CCC(CC2)N3CCN(CC3)S(=O)(=O)C)OC)NC4=NC=CC(=N4)C5=C(N=C6N5C=CC=C6)C7=CC(=C(C=C7)OC)C(=O)NC8=C(C=CC=C8F)F

Solubility

In vitro
Batch:

DMSO : 124 mg/mL ( (145.54 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.250mg/ml (4.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 85 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.000mg/ml (1.17mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	Insulin Receptor ^[1] (Cell-free assay) 25 nM IGF-1R ^[1] (Cell-free assay) 27 nM
In vitro	GSK1904529A is a reversible, ATP-competitive inhibitor and has enzyme-inhibitor binding values against IGF-1R and IR with K_i of 1.6 nM and 1.3 nM, respectively. This compound potently inhibits the ligand-induced phosphorylation of IGF-1R and IR at concentrations above 0.01 μM, followed by blocking downstream signaling (AKT, IRS-1, and ERK). It potently inhibits NIH-3T3/LISN, TC-71, SK-N-MC, SK-ES RD-ES cells with IC50 of 60 nM, 35 nM, 43 nM, 61 nM and 62 nM, respectively. This inhibitor also inhibits other multiple myeloma and Ewing's sarcoma cell lines including NCI-H929, MOLP-8, LP-1 and KMS-12-BM etc. It induces cell cycle arrest at the G1 phase in cell lines COLO 205, MCF-7, and NCI-H929, which are sensitive to this compound. ^[1]
Kinase Assay	Kinase assays
Kinase Assay	GSK1904529A is dissolved in DMSO as stock solution at 10 mM. Baculovirus-expressed glutathione S-transferase-tagged proteins encoding the intracellular domain of IGF-1R (amino acids 957-1367) and IR (amino acids 979-1382) are used for determination of IC50. Kinases are activated by preincubating the enzyme (2.7 μM final concentration) in 50 mM HEPES (pH 7.5), 10 mM MgCl₂, 0.1mg/mL bovine serum albumin, and 2 mM ATP. This compound is diluted in DMSO and dispensed into the assay plates (100 nL/well). Kinase reactions contained (in 10 μL) 50 mM HEPES (pH 7.5), 3 mM DTT, 0.1mg/mL bovine serum albumin, 1mM CHAPS, 10 mM MgCl₂, 10 μM ATP, 500 nM substrate peptide (biotin-aminohexylAEEEEYMMMMAKKKK-NH2; QPC), and 0.5 nM activated enzyme. Reactions are stopped after 1 hour at room temperature with 33 μM EDTA. Peptide phosphorylation is measured by time-resolved fluorescence resonance energy transfer with 7 nM streptavidin Surelight allophycocyanin and 1nM europium-conjugated phosphotyrosine antibodies. Plates are read in a multilabel reader.
In vivo	GSK1904529A indicates 98% tumor growth inhibition in NIH-3T3/LISN tumor-bearing mice at a dose of 30 mg/kg (orally, twice-daily) and 75% in COLO 205 xenografts mice (once daily). Among HT29 and BxPC3 xenografts, this compound produces moderate tumor growth inhibition with no side effects at a dose of 30 mg/kg. Meanwhile, it shows minimal effects on blood glucose levels. This compound (~3.5 μM in blood) completely inhibits IGF-1R phosphorylation. It has been implicated in treatment of various IGF-1R-dependent tumors including prostate, colon, breast, pancreatic, ovarian, and sarcomas. ^[1]
References	https://pubmed.ncbi.nlm.nih.gov/19383820/

Applications

Methods	Biomarkers	Images	PMID
Growth inhibition assay	Cell number		28572530

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):