GSK1838705A
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MedKoo CAT#: 401475

CAS#: 1116235-97-2

Description: GSK1838705A is a small-molecule kinase inhibitor that inhibits IGF-IR and IR (insulin receptor) with IC50s of 2.0 and 1.6 nM, respectively . GSK1838705A blocks the in vitro proliferation of cell lines derived from solid and hematologic malignancies, including multiple myeloma and Ewing's sarcoma, and retards the growth of human tumor xenografts in vivo. Despite the inhibitory effect of GSK1838705A on insulin receptor, minimal effects on glucose homeostasis were observed at efficacious doses. GSK1838705A also inhibits the anaplastic lymphoma kinase (ALK), which drives the aberrant growth of anaplastic large-cell lymphomas, some neuroblastomas, and a subset of non-small cell lung cancers. GSK1838705A inhibits ALK, with an IC(50) of 0.5 nmol/L, and causes complete regression of ALK-dependent tumors in vivo at well-tolerated doses. GSK1838705A is therefore a promising antitumor agent for therapeutic use in human cancers. (source: Mol Cancer Ther. 2009 Oct;8(10):2811-20).


Chemical Structure

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GSK1838705A
CAS# 1116235-97-2

Theoretical Analysis

MedKoo Cat#: 401475
Name: GSK1838705A
CAS#: 1116235-97-2
Chemical Formula: C27H29FN8O3
Exact Mass: 532.23467
Molecular Weight: 532.57
Elemental Analysis: C, 60.89; H, 5.49; F, 3.57; N, 21.04; O, 9.01

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Same day
25.0mg USD 150.0 Same day
50.0mg USD 250.0 Same day
100.0mg USD 450.0 Same day
200.0mg USD 850.0 Same day
500.0mg USD 1850.0 Same day
1.0g USD 3250.0 Same day
2.0g USD 5450.0 Same day
5.0g USD 11950.0 2 weeks
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Synonym: GSK1838705A; GSK-1838705A; GSK 1838705A.

IUPAC/Chemical Name: 2-((2-((1-(2-(dimethylamino)acetyl)-5-methoxyindolin-6-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-6-fluoro-N-methylbenzamide

InChi Key: HZTYDQRUAWIZRE-UHFFFAOYSA-N

InChi Code: InChI=1S/C27H29FN8O3/c1-29-26(38)23-17(28)6-5-7-18(23)31-25-16-8-10-30-24(16)33-27(34-25)32-19-13-20-15(12-21(19)39-4)9-11-36(20)22(37)14-35(2)3/h5-8,10,12-13H,9,11,14H2,1-4H3,(H,29,38)(H3,30,31,32,33,34)

SMILES Code: O=C(NC)C1=C(F)C=CC=C1NC2=C3C(NC=C3)=NC(NC4=CC5=C(C=C4OC)CCN5C(CN(C)C)=O)=N2

Appearance: white solid powder

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, 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

Biological target: GSK1838705A is a reversible IGF-IR and insulin receptor inhibitor with IC50s of 2.0 and 1.6 nM, respectively.
In vitro activity: As shown in Figure 2A and B, the subG1 DNA content in PC-3R cells significantly increased after treatment with GSK1838705A when compared with the control group (P<0.01). This study also observed the nuclear morphology in PC-3R cells after treatment with GSK1838705A. After treatment with GSK1838705A, the PC-3R cell nuclei showed consistent morphological changes, including chromatin condensation and nuclear fragmentation, both of which are indicators of cell apoptosis (Figure 2C and D). GSK1838705A-induced cell apoptosis was also confirmed by TUNEL staining assay (Figure 2C). These structural alterations indicate that treatment with GSK1838705A generated apoptosis in docetaxel-resistant PC-3R cells. Further, Western blot analysis showed that treatment with GSK1838705A significantly increased levels of cleaved caspase-3 in resistant cells (Figure 2E), further confirming GSK1838705A-induced apoptosis in resistant cells. Reference: Onco Targets Ther. 2015; 8: 753–760. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403692/
In vivo activity: GSK1838705A significantly inhibited the growth of the tumor mass. Treatment with GSK1838705A at 4 or 8 mg/kg resulted in reductions of ~45 and 85% in tumor volume, respectively, 11 days after the first administration (Fig. 4A). No significant weight loss was observed in either treatment group during the course of treatment, indicating that the concentrations of GSK1838705A used were well tolerated by the recipient mice, and no significant cytotoxicity accompanied the GSK1838705A treatment (Fig. 4B). Consistent with the results of the in vitro investigations, GSK1838705A induced significant apoptosis in the tumor cells. Following treatment of tumors with 8 mg/kg GSK1838705A, significant DNA fragmentation was detected using a TUNEL assay and nuclear staining (Fig. 4C). Taken together, these results provided clear evidence indicating that GSK1838705A effectively suppressed the growth of the tumor in vivo by inducing apoptosis of the tumor cells. Reference: Mol Med Rep. 2015 Oct; 12(4): 5641–5646. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581800/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 73.32 137.67
DMSO:PBS (pH 7.2) (1:3) 0.25 0.47
DMF 25.0 46.94
Ethanol 2.0 3.76

Preparing Stock Solutions

The following data is based on the product molecular weight 532.57 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. Zhou F, Chen X, Fan S, Tai S, Jiang C, Zhang Y, Hao Z, Zhou J, Shi H, Zhang L, Liang C. GSK1838705A, an insulin-like growth factor-1 receptor/insulin receptor inhibitor, induces apoptosis and reduces viability of docetaxel-resistant prostate cancer cells both in vitro and in vivo. Onco Targets Ther. 2015 Apr 10;8:753-60. doi: 10.2147/OTT.S79105. PMID: 25926740; PMCID: PMC4403692. 2. Sabbatini P, Korenchuk S, Rowand JL, Groy A, Liu Q, Leperi D, Atkins C, Dumble M, Yang J, Anderson K, Kruger RG, Gontarek RR, Maksimchuk KR, Suravajjala S, Lapierre RR, Shotwell JB, Wilson JW, Chamberlain SD, Rabindran SK, Kumar R. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20. doi: 10.1158/1535-7163.MCT-09-0423. PMID: 19825801. 3. Zhou X, Shen F, Ma P, Hui H, Pei S, Chen M, Wang Z, Zhou W, Jin B. GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo. Mol Med Rep. 2015 Oct;12(4):5641-6. doi: 10.3892/mmr.2015.4129. Epub 2015 Jul 28. PMID: 26238593; PMCID: PMC4581800.
In vitro protocol: 1. Zhou F, Chen X, Fan S, Tai S, Jiang C, Zhang Y, Hao Z, Zhou J, Shi H, Zhang L, Liang C. GSK1838705A, an insulin-like growth factor-1 receptor/insulin receptor inhibitor, induces apoptosis and reduces viability of docetaxel-resistant prostate cancer cells both in vitro and in vivo. Onco Targets Ther. 2015 Apr 10;8:753-60. doi: 10.2147/OTT.S79105. PMID: 25926740; PMCID: PMC4403692. 2. Sabbatini P, Korenchuk S, Rowand JL, Groy A, Liu Q, Leperi D, Atkins C, Dumble M, Yang J, Anderson K, Kruger RG, Gontarek RR, Maksimchuk KR, Suravajjala S, Lapierre RR, Shotwell JB, Wilson JW, Chamberlain SD, Rabindran SK, Kumar R. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20. doi: 10.1158/1535-7163.MCT-09-0423. PMID: 19825801.
In vivo protocol: 1. Zhou X, Shen F, Ma P, Hui H, Pei S, Chen M, Wang Z, Zhou W, Jin B. GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo. Mol Med Rep. 2015 Oct;12(4):5641-6. doi: 10.3892/mmr.2015.4129. Epub 2015 Jul 28. PMID: 26238593; PMCID: PMC4581800. 2. Zhou F, Chen X, Fan S, Tai S, Jiang C, Zhang Y, Hao Z, Zhou J, Shi H, Zhang L, Liang C. GSK1838705A, an insulin-like growth factor-1 receptor/insulin receptor inhibitor, induces apoptosis and reduces viability of docetaxel-resistant prostate cancer cells both in vitro and in vivo. Onco Targets Ther. 2015 Apr 10;8:753-60. doi: 10.2147/OTT.S79105. PMID: 25926740; PMCID: PMC4403692

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1: Bao NR, Lu M, Bin FW, Chang ZY, Meng J, Zhou LW, Guo T, Zhao JN. Systematic screen with kinases inhibitors reveals kinases play distinct roles in growth of osteoprogenitor cells. Int J Clin Exp Pathol. 2013 Sep 15;6(10):2082-91. eCollection 2013. PubMed PMID: 24133586; PubMed Central PMCID: PMC3796230.

2: Ardini E, Magnaghi P, Orsini P, Galvani A, Menichincheri M. Anaplastic Lymphoma Kinase: role in specific tumours, and development of small molecule inhibitors for cancer therapy. Cancer Lett. 2010 Dec 28;299(2):81-94. doi: 10.1016/j.canlet.2010.09.001. Epub 2010 Oct 8. Review. PubMed PMID: 20934803.

3: Kelleher FC, McDermott R. The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene. Eur J Cancer. 2010 Sep;46(13):2357-68. doi: 10.1016/j.ejca.2010.04.006. Epub 2010 May 5. Review. PubMed PMID: 20451371.

4: Sabbatini P, Korenchuk S, Rowand JL, Groy A, Liu Q, Leperi D, Atkins C, Dumble M, Yang J, Anderson K, Kruger RG, Gontarek RR, Maksimchuk KR, Suravajjala S, Lapierre RR, Shotwell JB, Wilson JW, Chamberlain SD, Rabindran SK, Kumar R. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20. doi: 10.1158/1535-7163.MCT-09-0423. PubMed PMID: 19825801.



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