Synonym
I-OMe-AG538; I OMe-AG538; IOMe-AG538; I-OMeAG538; I-OMe AG538; I OMe AG538; IOMeAG538; I-OMe-Tyrphostin AG538; IOMeTyrphostin AG538; I OMe Tyrphostin AG538;
IUPAC/Chemical Name
(E)-2-(3,4-dihydroxybenzoyl)-3-(4-hydroxy-3-iodo-5-methoxyphenyl)acrylonitrile
InChi Key
HSRMHXWCTRFVHK-NYYWCZLTSA-N
InChi Code
InChI=1S/C17H12INO5/c1-24-15-6-9(5-12(18)17(15)23)4-11(8-19)16(22)10-2-3-13(20)14(21)7-10/h2-7,20-21,23H,1H3/b11-4+
SMILES Code
N#C/C(C(C1=CC=C(O)C(O)=C1)=O)=C\C2=CC(OC)=C(O)C(I)=C2
Purity
>98% (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
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
Biological target:
I-OMe-Tyrphostin AG 538 (I-OMe-AG 538) is a specific inhibitor of IGF-1R (insulin-like growth factor-1 receptor tyrosine kinase). I-OMe-Tyrphostin AG 538 inhibits IGF-1R-mediated signaling and is preferentially cytotoxic to nutrient-deprived PANC1 cells. I-OMe-Tyrphostin AG 538 is an ATP-competitive inhibitor of phosphatidylinositol-5-phosphate 4-kinase α (PI5P4Kα), with an IC50 of 1 µM.
In vitro activity:
To confirm the inhibitory activity of I-OMe AG538 toward IGF-1R kinase and signaling, starved BMSCs were treated with doses of 300 nmol/l for 3 h followed by stimulation with IGF-1 for 5 to 30 min. Fig. 6 shows that both IGF-1R autophosphorylation and the two major IGF-1R-related intracellular signaling pathways, MAPK and PI3K pathways, were inhibited by I-OMe AG538.
Reference: Mol Med Rep. 2017 Jul;16(1):787-793. https://pubmed.ncbi.nlm.nih.gov/28560388/
In vivo activity:
I-OMe-AG538-treated nondiabetic and diabetic groups showed significant increases in insulin level, HOMA-IR, and HOMA-β compared to normal control. Also, diabetic rats injected with I-OMe-AG538 showed a reduction in expression of IGF-1, PI3K, and IR (5.6-, 2.2-, and 1.8-fold, resp.) and an increase in the ratio of insulin/IR (33.3-fold) compared to normal control.
Reference: Oxid Med Cell Longev. 2016;2016:2492107. https://pubmed.ncbi.nlm.nih.gov/27579151/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
50.0 |
114.37 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
437.19
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.
| 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. Gong H, Wang X, Wang L, Liu Y, Wang J, Lv Q, Pang H, Zhang Q, Wang Z. Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1. Mol Med Rep. 2017 Jul;16(1):787-793. doi: 10.3892/mmr.2017.6639. Epub 2017 May 26. PMID: 28560388; PMCID: PMC5482190.
2. Balbaa M, El-Zeftawy M, Ghareeb D, Taha N, Mandour AW. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet. Oxid Med Cell Longev. 2016;2016:2492107. doi: 10.1155/2016/2492107. Epub 2016 Aug 4. PMID: 27579151; PMCID: PMC4989085.
In vitro protocol:
1. Gong H, Wang X, Wang L, Liu Y, Wang J, Lv Q, Pang H, Zhang Q, Wang Z. Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1. Mol Med Rep. 2017 Jul;16(1):787-793. doi: 10.3892/mmr.2017.6639. Epub 2017 May 26. PMID: 28560388; PMCID: PMC5482190.
In vivo protocol:
1. Balbaa M, El-Zeftawy M, Ghareeb D, Taha N, Mandour AW. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet. Oxid Med Cell Longev. 2016;2016:2492107. doi: 10.1155/2016/2492107. Epub 2016 Aug 4. PMID: 27579151; PMCID: PMC4989085.
1: Gong H, Wang X, Wang L, Liu Y, Wang J, Lv Q, Pang H, Zhang Q, Wang Z. Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1. Mol Med Rep. 2017 Jul;16(1):787-793. doi: 10.3892/mmr.2017.6639. Epub 2017 May 26. PMID: 28560388; PMCID: PMC5482190.
2: Balbaa M, El-Zeftawy M, Ghareeb D, Taha N, Mandour AW. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet. Oxid Med Cell Longev. 2016;2016:2492107. doi: 10.1155/2016/2492107. Epub 2016 Aug 4. PMID: 27579151; PMCID: PMC4989085.
3: Wang XL, Li CM, Lü Q, Wang L, Wang J, Gong HB. [Insulin-like growth factor 1 induces bone mesenchymal stem cells differentiation into cardiomyocyte-like cells]. Zhonghua Xin Xue Guan Bing Za Zhi. 2013 Feb;41(2):150-5. Chinese. PMID: 23710747.
4: Momose I, Kunimoto S, Osono M, Ikeda D. Inhibitors of insulin-like growth factor-1 receptor tyrosine kinase are preferentially cytotoxic to nutrient- deprived pancreatic cancer cells. Biochem Biophys Res Commun. 2009 Feb 27;380(1):171-6. doi: 10.1016/j.bbrc.2009.01.065. Epub 2009 Jan 21. PMID: 19166817.
5: Liu H, Yang H, Wang D, Liu Y, Liu X, Li Y, Xie L, Wang G. Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappaB pathway but not a PI3K/Akt pathway. Eur J Pharmacol. 2009 Jan 14;602(2-3):277-82. doi: 10.1016/j.ejphar.2008.11.026. Epub 2008 Nov 21. PMID: 19049803.
6: Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005 Dec 1;65(23):11118-28. doi: 10.1158/0008-5472.CAN-04-3841. Erratum in: Cancer Res. 2008 Nov 15;68(22):9566. PMID: 16322262.
7: Nemoto E, Shimonishi M, Nitta Y, Shimauchi H. The involvement of platelet- derived growth factor receptors and insulin-like growth factor-I receptors signaling during mineralized nodule formation by human periodontal ligament cells. J Periodontal Res. 2004 Dec;39(6):388-97. doi: 10.1111/j.1600-0765.2004.00750.x. PMID: 15491343.
8: Hallak H, Moehren G, Tang J, Kaou M, Addas M, Hoek JB, Rubin R. Epidermal growth factor-induced activation of the insulin-like growth factor I receptor in rat hepatocytes. Hepatology. 2002 Dec;36(6):1509-18. doi: 10.1053/jhep.2002.37138. PMID: 12447877.
