GSK2256098 | CAS#1224887-10-8 | FAK Inhibitor

MedKoo Cat#: 205482 | Name: GSK-2256098

Description:

WARNING: This product is for research use only, not for human or veterinary use.

GSK2256098, also known as GTPL7939, is a focal adhesion kinase-1 (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. FAK inhibitor GSK2256098 inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including ERK, JNK/MAPK and PI3K/Akt, thereby inhibiting tumor cell migration, proliferation and survival, and tumor angiogenesis. The tyrosine kinase FAK is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types.

Chemical Structure

GSK-2256098

CAS#1224887-10-8 (free base)

Theoretical Analysis

MedKoo Cat#: 205482

Name: GSK-2256098

CAS#: 1224887-10-8 (free base)

Chemical Formula: C20H23ClN6O2

Exact Mass: 414.1571

Molecular Weight: 414.89

Elemental Analysis: C, 57.90; H, 5.59; Cl, 8.54; N, 20.26; O, 7.71

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship

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Related CAS #

1416771-10-2 (HCl) 1224887-10-8 (free base)

Synonym

GSK2256098; GSK 2256098; GSK-2256098; GTPL7939; GTPL-7939; GTP L7939.

IUPAC/Chemical Name

2-((5-chloro-2-((1-isopropyl-3-methyl-1H-pyrazol-5-yl)amino)pyridin-4-yl)amino)-N-methoxybenzamide

InChi Key

BVAHPPKGOOJSPU-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H23ClN6O2/c1-12(2)27-19(9-13(3)25-27)24-18-10-17(15(21)11-22-18)23-16-8-6-5-7-14(16)20(28)26-29-4/h5-12H,1-4H3,(H,26,28)(H2,22,23,24)

SMILES Code

CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C

Appearance

White to off-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

More Info

Interim Clinical trial results with GSK2256098 : 57 pts with advanced solid tumors have been treated at escalating doses ranging from 80 mg to 1500 mg BID: median age=58.8 (range 21-84). The most common tumor types include: mesothelioma (23), ovary (7), colon (3), kidney (3), and pancreas (3). MTD was determined to be 1000 mg BID. DLTs were Gr 2 proteinuria (1000 mg), Gr 2 nausea, vomiting, fatigue (1250 mg) and Gr 3 asthenia (1500 mg). Most frequent toxicities were nausea (32 pts, 56%), diarrhea (31 pts, 54%), vomiting (25 pts, 44%), decreased appetite (18 pts 32%) and asthenia (11 pts, 19%). The majority of toxicities were Gr 1-2; Gr 3 drug-related events included hypertriglyceridemia (n=2), hyperlipasemia (2), asthenia (1), increased amylase (1), and loss of consciousness (1). Few dose reductions and interruptions have occurred. Minor responses/stable disease (SD) were observed in pts with mesothelioma (-12%, 27 wks), melanoma (-26%, 54 wks), and naso/pharyngeal cancer (-31% target lesion, 30 wks) and SD in renal cell (48+ wks). In preliminary analysis of single-dose PK, exposure generally increased in a dose-proportional manner, and the geometric mean tÅ“ was 4.2 h. Accumulation was not observed with repeat dosing. Conclusions: GSK2256098 is well tolerated with evidence of clinical activity. PK supports BID dosing. (source: J Clin Oncol 30, 2012 (suppl; abstr 3000)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC60822

QC Data

View QC data: current batch, Lot#BBC60822

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

FAK kinase inhibitor with Ki of 0.4 nM.

In vitro activity:

Focal adhesion kinase (FAK) hyperactivation is common in pancreatic ductal adenocarcinoma (PDAC). GSK2256098 inhibits FAK activity through targeting the phosphorylation site of FAK, tyrosine (Y) 397. In order to determine whether GSK2256098 inhibition of FAK Y397 phosphorylation attenuates PDAC-associated cell proliferation, motility and survival, cultured PDAC cells were used as cellular models of GSK2256098-impaired abnormal growth. Western blot analysis, cell viability analysis, clonogenic survival, soft-agar and wound healing assays were performed. GSK2256098 inhibition of FAK Y397 phosphorylation correlated with decreased levels of phosphorylated Akt and ERK in L3.6P1 cells. GSK2256098 decreased cell viability, anchorage-independent growth, and motility in a dose dependent manner. Reference: Cell Cycle. 2014;13(19):3143-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615113/

In vivo activity:

To examine the effect of GSK2256098 in pre-clinical models of uterine cancer, orthotopic mouse models of uterine cancer were used. Mice were inoculated with Ishikawa or Hec1a cells. In the Ishikawa model, tumor growth was inhibited to a greater extent in the GSK2256098 monotherapy group (Fig. 3A) as compared to the Hec1A model (Fig. 3B). Extent of distant metastases was also substantially reduced with GSK2256098-based therapy. All tumor models in mice treated with GSK2256098 exhibited less proliferation via Ki67 than control. Ishikawa tumors had the lowest Ki67 expression in response to therapy. Ishikawa tumors had higher apoptotic indices than Hec1A tumors after treatment with GSK2256098. Reference: Mol Cancer Ther. 2015 Jun;14(6):1466-1475. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458384/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.3	114.08
	DMF	30.0	72.31
	Ethanol	56.0	134.98
	Ethanol:PBS (pH 7.2) (1:4)	0.2	0.48

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 414.89 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. Zhang J, He DH, Zajac-Kaye M, Hochwald SN. A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9. doi: 10.4161/15384101.2014.949550. PMID: 25486573; PMCID: PMC4615113. 2. Thanapprapasr D, Previs RA, Hu W, Ivan C, Armaiz-Pena GN, Dorniak PL, Hansen JM, Rupaimoole R, Huang J, Dalton HJ, Ali-Fehmi R, Coleman RL, Sood AK. PTEN Expression as a Predictor of Response to Focal Adhesion Kinase Inhibition in Uterine Cancer. Mol Cancer Ther. 2015 Jun;14(6):1466-1475. doi: 10.1158/1535-7163.MCT-14-1077. Epub 2015 Apr 1. PMID: 25833835; PMCID: PMC4458384.

In vitro protocol:

In vivo protocol:

1. Thanapprapasr D, Previs RA, Hu W, Ivan C, Armaiz-Pena GN, Dorniak PL, Hansen JM, Rupaimoole R, Huang J, Dalton HJ, Ali-Fehmi R, Coleman RL, Sood AK. PTEN Expression as a Predictor of Response to Focal Adhesion Kinase Inhibition in Uterine Cancer. Mol Cancer Ther. 2015 Jun;14(6):1466-1475. doi: 10.1158/1535-7163.MCT-14-1077. Epub 2015 Apr 1. PMID: 25833835; PMCID: PMC4458384.

1: Thanapprapasr D, Previs RA, Hu W, Ivan C, Armaiz-Pena GN, Dorniak PL, Hansen JM, Rupaimoole R, Huang J, Dalton HJ, Ali-Fehmi R, Coleman RL, Sood AK. PTEN Expression as a Predictor of Response to Focal Adhesion Kinase Inhibition in Uterine Cancer. Mol Cancer Ther. 2015 Jun;14(6):1466-75. doi: 10.1158/1535-7163.MCT-14-1077. Epub 2015 Apr 1. PubMed PMID: 25833835; PubMed Central PMCID: PMC4458384. 2: Zhang J, He DH, Zajac-Kaye M, Hochwald SN. A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9. doi: 10.4161/15384101.2014.949550. PubMed PMID: 25486573; PubMed Central PMCID: PMC4615113. 3: Schultze A, Fiedler W. Clinical importance and potential use of small molecule inhibitors of focal adhesion kinase. Anticancer Agents Med Chem. 2011 Sep;11(7):593-9. Review. PubMed PMID: 21787277.