GSK-1904529a
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MedKoo CAT#: 401480

CAS#: 1089283-49-7

Description: GSK-1904529A, also known as GSK 4529, is an IGF-1R Inhibitor, is is a promising candidate for therapeutic use in IGF-IR–dependent tumors. GSK1904529A selectively inhibits IGF-IR and IR with IC50s of 27 and 25 nmol/L, respectively. GSK1904529A blocks receptor autophosphorylation and downstream signaling, leading to cell cycle arrest. It inhibits the proliferation of cell lines derived from solid and hematologic malignancies, with multiple myeloma and Ewing's sarcoma cell lines being most sensitive. Oral administration of GSK1904529A decreases the growth of human tumor xenografts in mice, consistent with a reduction of IGF-IR phosphorylation in tumors. Despite the potent inhibitory activity of GSK1904529A on IR in vitro and in vivo , minimal effects on blood glucose levels are observed in animals at doses that show significant antitumor activity. (source: Clin Cancer Res May 1, 2009 15; 3058 )


Chemical Structure

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GSK-1904529a
CAS# 1089283-49-7

Theoretical Analysis

MedKoo Cat#: 401480
Name: GSK-1904529a
CAS#: 1089283-49-7
Chemical Formula: C44H47F2N9O5S
Exact Mass: 851.33889
Molecular Weight: 851.96309
Elemental Analysis: C, 62.03; H, 5.56; F, 4.46; N, 14.80; O, 9.39; S, 3.76

Price and Availability

Size Price Availability Quantity
5.0mg USD 300.0 2 Weeks
10.0mg USD 550.0 2 Weeks
25.0mg USD 950.0 2 Weeks
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Synonym: GSK 4529; GSK4529; GSK-4529; GSK1904529a; GSK 1904529; GSK-1904529a .

IUPAC/Chemical Name: N-(2,6-Difluorophenyl)-5-[3-[2-[[5-ethyl-2-(methyloxy)-4-[4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl]phenyl]amino]-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)benzamide

InChi Key: MOSKATHMXWSZTQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C44H47F2N9O5S/c1-5-28-26-35(38(60-3)27-36(28)53-19-15-30(16-20-53)52-21-23-54(24-22-52)61(4,57)58)49-44-47-17-14-34(48-44)42-40(50-39-11-6-7-18-55(39)42)29-12-13-37(59-2)31(25-29)43(56)51-41-32(45)9-8-10-33(41)46/h6-14,17-18,25-27,30H,5,15-16,19-24H2,1-4H3,(H,51,56)(H,47,48,49)

SMILES Code: O=C(NC1=C(F)C=CC=C1F)C2=CC(C3=C(C4=NC(NC5=CC(CC)=C(N6CCC(N7CCN(S(=O)(C)=O)CC7)CC6)C=C5OC)=NC=C4)N8C=CC=CC8=N3)=CC=C2OC

Appearance: Solid powder

Purity: >95% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: GSK1904529A is a potent, selective, orally active, and ATP-competitive inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR), with IC50s of 27 and 25 nM, respectively. GSK1904529A shows poor activity (IC50>1 μM) in 45 other serine/threonine and tyrosine kinases.
In vitro activity: Cell counting assay results in Figure 1A demonstrated that treatment GSK1904529A, at 50/250 nM, significantly inhibited Saos-2 cell proliferation. The number of viable Saos-2 cells was significantly reduced following GSK1904529A (50/250 nM) treatment, at 30-, 60-, and 90-hour durations (Figure 1A). GSK1904529A displayed a concentration-dependent manner in inhibiting Saos-2 cell proliferation (Figure 1A). Treatment with GSK1904529A in Saos-2 cells also dramatically decreased MTT OD (Figure 1B) and number of colonies (Figure 1C). GSK1904529A at 250 nM was again more potent than 50 nM in inhibiting Saos-2 cell proliferation (Figure 1B and 1C). Reference: Oncotarget. 2017 Jul 25;8(30):49646-49654. https://pubmed.ncbi.nlm.nih.gov/28572530/
In vivo activity: The data revealed that the mice treated with GSK1904529A exhibited substantially reduced tumor volumes compared with the vehicle-treated group (Fig. 4A). The suppression of tumor growth was correlated with the dose of GSK1904529A (Fig. 4A). In addition, the treatment was well tolerated, as no weight loss was observed (Fig. 4B). Further investigation revealed that treatment with GSK1904529A induced marked apoptosis in the tumor cells (Fig. 4C), which was consistent with the in vitro data. Taken together, these data suggested that GSK1904529A markedly inhibited glioma tumor growth in vivo. Reference: Mol Med Rep. 2015 Sep;12(3):3381-3385. https://pubmed.ncbi.nlm.nih.gov/26035416/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF:PBS (pH 7.2) 0.8 0.94
DMSO 110.0 129.11

Preparing Stock Solutions

The following data is based on the product molecular weight 851.96309 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Fei HD, Yuan Q, Mao L, Chen FL, Cui ZH, Tao S, Ji F. Assessment of GSK1904529A as a promising anti-osteosarcoma agent. Oncotarget. 2017 Jul 25;8(30):49646-49654. doi: 10.18632/oncotarget.17911. PMID: 28572530; PMCID: PMC5564795. 2. Gupta P, Xie M, Narayanan S, Wang YJ, Wang XQ, Yuan T, Wang Z, Yang DH, Chen ZS. GSK1904529A, a Potent IGF-IR Inhibitor, Reverses MRP1-Mediated Multidrug Resistance. J Cell Biochem. 2017 Oct;118(10):3260-3267. doi: 10.1002/jcb.25975. Epub 2017 May 3. PMID: 28266043; PMCID: PMC5589182. 3. Zhou Q, Zhang J, Cui Q, Li X, Gao G, Wang Y, Xu Y, Gao X. GSK1904529A, an insulin-like growth factor-1 receptor inhibitor, inhibits glioma tumor growth, induces apoptosis and inhibits migration. Mol Med Rep. 2015 Sep;12(3):3381-3385. doi: 10.3892/mmr.2015.3869. Epub 2015 May 28. PMID: 26035416; PMCID: PMC4526077.
In vitro protocol: 1. Fei HD, Yuan Q, Mao L, Chen FL, Cui ZH, Tao S, Ji F. Assessment of GSK1904529A as a promising anti-osteosarcoma agent. Oncotarget. 2017 Jul 25;8(30):49646-49654. doi: 10.18632/oncotarget.17911. PMID: 28572530; PMCID: PMC5564795. 2. Gupta P, Xie M, Narayanan S, Wang YJ, Wang XQ, Yuan T, Wang Z, Yang DH, Chen ZS. GSK1904529A, a Potent IGF-IR Inhibitor, Reverses MRP1-Mediated Multidrug Resistance. J Cell Biochem. 2017 Oct;118(10):3260-3267. doi: 10.1002/jcb.25975. Epub 2017 May 3. PMID: 28266043; PMCID: PMC5589182.
In vivo protocol: 1. Fei HD, Yuan Q, Mao L, Chen FL, Cui ZH, Tao S, Ji F. Assessment of GSK1904529A as a promising anti-osteosarcoma agent. Oncotarget. 2017 Jul 25;8(30):49646-49654. doi: 10.18632/oncotarget.17911. PMID: 28572530; PMCID: PMC5564795. 2. Zhou Q, Zhang J, Cui Q, Li X, Gao G, Wang Y, Xu Y, Gao X. GSK1904529A, an insulin-like growth factor-1 receptor inhibitor, inhibits glioma tumor growth, induces apoptosis and inhibits migration. Mol Med Rep. 2015 Sep;12(3):3381-3385. doi: 10.3892/mmr.2015.3869. Epub 2015 May 28. PMID: 26035416; PMCID: PMC4526077.

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1: Sabbatini P, Rowand JL, Groy A, Korenchuk S, Liu Q, Atkins C, Dumble M, Yang J, Anderson K, Wilson BJ, Emmitte KA, Rabindran SK, Kumar R. Antitumor activity of GSK1904529A, a small-molecule inhibitor of the insulin-like growth factor-I eceptor tyrosine kinase. Clin Cancer Res. 2009 May 1;15(9):3058-67. Epub 2009 Apr 21. PubMed PMID: 19383820.



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