4506-66-5 Usage
Description
1,2,4,5-Benzenetetramine tetrahydrochloride, also known as FAK Inhibitor 14, is a cell-permeable tetraamine compound identified through computer-aided molecular docking screening based on its interaction with the Y397 site of focal adhesion kinase (FAK). It is a selective FAK inhibitor that displays no significant activity against a range of other kinases, including EGFR, PDGFR, and IGF-R. 1,2,4,5-Benzenetetramine tetrahydrochloride has been shown to inhibit FAK autophosphorylation and its kinase activity towards paxillin phosphorylation in cell-free kinase assays and in BT474 breast cancer cultures.
Uses
Used in Cancer Therapy:
1,2,4,5-Benzenetetramine tetrahydrochloride is used as an FAK inhibitor for directly blocking phosphorylation of focal adhesion kinase (FAK) in a doseand time-dependent manner. It has demonstrated tumor regression in breast cancer in vivo and has been suggested for use in cancer therapy.
Used in Metastasis Assay:
1,2,4,5-Benzenetetramine tetrahydrochloride is used as a tool in the metastasis assay to study its effect on bone morphogenetic protein 7 (BMP-7)-induced cell crawling and adhesion.
Used in Anticancer Applications:
In the field of cancer research, 1,2,4,5-Benzenetetramine tetrahydrochloride is used as an antiproliferative agent for its ability to inhibit the proliferation of various human tumor cell lines in vitro and in breast cancer cells in vivo. It has also been shown to induce regression of pancreatic tumors and glioblastoma, as well as display antiangiogenic activity.
Used in Drug Development:
1,2,4,5-Benzenetetramine tetrahydrochloride is used as a lead compound in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles have been employed as carriers for the delivery of this compound, aiming to improve its delivery, bioavailability, and therapeutic outcomes.
Biological Activity
Selective focal adhesion kinase (FAK) inhibitor that displays no significant activity at a range of other kinases including EGFR, PDGFR and IGF-RI. Prevents FAK autophosphorylation at Y397 (IC 50 = 1 μ M), promotes cell detachment and inhibits cell adhesion in vitro . Exhibits antiproliferative activity in a variety of human tumor cell lines in vitro and in breast cancer cells in vivo .
Biochem/physiol Actions
1,2,4,5-Benzenetetraamine tetrahydrochloride (FAK Inhibitor 14; Y15) is a cell-permeable, selective focal adhesion kinase (FAK) inhibitor. Focal adhesion kinase (FAK) is essential in regulating integrin signaling pathways responsible for cell survival, cell proliferation and motility. Phosphorylation of FAK tyrosine 397 (Y397) forms a high affinity binding site for the SH2 domain of the Src family kinases and PI3 kinase. FAK is overexpressed in a number of human tumors. 1,2,4,5-Benzenetetraamine tetrahydrochloride (FAK Inhibitor 14, Y15) blocks phosphorylation of Y397-FAK, which results in neuroblastoma cell detachment and apoptosis.
References
1) Golubovskaya et al. (2008), A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth; J. Med. Chem., 51 7405
2) Hochwald et al. (2009), A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer; Cell Cycle, 8 2435
3) Golubovskaya et al. (2013), Pharmacologic blockade of FAK autophosphorylation decreases human glioblastoma tumor growth and synergizes with temozolomide; Mol. Cancer Ther., 12 162
4) Cabrita et al. (2011), Focal Adhesion kinase inhibitors are potent anti-angiogenic agents; Mol. Oncol., 5 517
Check Digit Verification of cas no
The CAS Registry Mumber 4506-66-5 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 4,5,0 and 6 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 4506-66:
(6*4)+(5*5)+(4*0)+(3*6)+(2*6)+(1*6)=85
85 % 10 = 5
So 4506-66-5 is a valid CAS Registry Number.
InChI:InChI=1/C6H10N4/c7-3-1-4(8)6(10)2-5(3)9/h1-2H,7-10H2
4506-66-5Relevant articles and documents
Benzobisimidazole Cruciform Fluorophores
Le, Ha T. M.,El-Hamdi, Nadia S.,Miljani?, Ognjen ?.
, p. 5210 - 5217 (2015/05/27)
A series of 11 cross-conjugated cruciform fluorophores based on a benzobisimidazole nucleus has been synthesized and characterized. Like in their previously reported benzobisoxazole counterparts, the HOMOs of these new fluorophores are localized along the vertical bisethynylbenzene axes, while their LUMOs remain relatively delocalized across the molecule, except in cruciforms substituted with electron-withdrawing groups along the vertical axis. Benzobisimidazole cruciforms exhibit a pronounced response to deprotonation in their UV/vis absorption and emission spectra, but their response to protonation is significantly attenuated. (Chemical Equation Presented).