WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205482
Description: 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.
MedKoo Cat#: 205482
Chemical Formula: C20H23ClN6O2
Exact Mass: 414.1571
Molecular Weight: 414.894
Elemental Analysis: C, 57.90; H, 5.59; Cl, 8.54; N, 20.26; O, 7.71
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
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)
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:
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.