136164-66-4 Usage
Uses
Used in Pharmaceutical Industry:
E 3330 is used as an active pharmaceutical ingredient for the inhibition of endothelial cancer cells and apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1). Its ability to inhibit APE1, an enzyme involved in DNA repair, makes it a potential therapeutic agent for cancer treatment.
Used in Ophthalmology:
E 3330 is used as a potent and selective APE1 inhibitor for the treatment of age-related macular degeneration (AMD). By inhibiting APE1, it can potentially reduce the progression of this vision-threatening condition.
Biological Activity
ap endonuclease 1 (ape1) is a dual-function protein, which contains a redox domain and a dna repair domain. ape1 is overexpressed in numerous solid cancers, including prostate and bladder cancers, non-small cell lung cancers, gliomas, medulloblastomas and primitive neurectodermal tumors, osteosarcomas, and germ cell tumors. e3330 is a small molecule inhibitor of redox activity of ape1 protein.
Biochem/physiol Actions
E3330 is a specific inhibitor of AP endonuclease 1 redox domain. E3330 inhibits APE-1 regulation of transcription factors, but does not affect Ape1 DNA repair activity. AP endonuclease 1 (APE1; also known as REF-1) is a multifunctional protein with dual functions in DNA repair and redox regulation of transcription factors. It is involved in apurinic/apyrimidinic endonuclease DNA base excision repair activity, in proofreading exonuclease activity, and in modulating DNA binding activity of several transcription factors including NF-κB, Egr-1, p53, AP-1, CREB, HIF-α, and members of the Pax family. APE1 is overexpressed in several human cancers, and disruption of APE1 function has detrimental effects on cancer cell viability. E3330 significantly reduces the growth of human pancreatic cancer cells in vitro and inhibits pancreatic cancer cell migration.
in vitro
e3330 significantly reduces the growth of human pancreatic cancer cells in vitro. this phenomenon was further confirmed by a small interfering rna experiment to knockdown ape1 expression in pancreatic cancer cells. furthermore, the growth-inhibitory effects of e3330 are accentuated by hypoxia, and this is accompanied by striking inhibition in the dna binding ability of hypoxia-inducible factor-1α [1].
in vivo
oral pretreatment with e3330 attenuated the elevation of plasma tumor necrosis factor activity and protected micefrom liver injury. furthermore, e3330 inhibited the production of tumor necrosis factor from cultured propionibacterium acnes-elicited murine peritoneal macrophages on stimulation with lipopolysaccharide in vitro [2].
references
[1] gang-ming zou and anirban maitra. small-molecule inhibitor of the ap endonuclease 1/ref-1 e3330 inhibits pancreatic cancer cell growth and migration. mol cancer ther. 2008 jul; 7(7): 2012–2021. [2] nagakawa j, hishinuma i, miyamoto k, hirota k, abe s, yamanaka t, katayama k, yamatsu i. protective effects of (2e)-3-[5-(2,3-dimethoxy-6-methyl-1,4- benzoquinoyl)]-2-nonyl-2-propenoic acid on endotoxin-mediated hepatitis in mice. j pharmacol exp ther. 1992 jul;262(1):145-50.
Check Digit Verification of cas no
The CAS Registry Mumber 136164-66-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,6,1,6 and 4 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 136164-66:
(8*1)+(7*3)+(6*6)+(5*1)+(4*6)+(3*4)+(2*6)+(1*6)=124
124 % 10 = 4
So 136164-66-4 is a valid CAS Registry Number.
InChI:InChI=1/C21H30O6/c1-5-6-7-8-9-10-11-12-15(21(24)25)13-16-14(2)17(22)19(26-3)20(27-4)18(16)23/h13H,5-12H2,1-4H3,(H,24,25)/b15-13+
136164-66-4Relevant articles and documents
Design and synthesis of novel quinone inhibitors targeted to the redox function of apurinic/apyrimidinic endonuclease 1/redox enhancing factor-1 (Ape1/Ref-1)
Nyland II, Rodney L.,Luo, Meihua,Kelley, Mark R.,Borch, Richard F.
experimental part, p. 1200 - 1210 (2010/07/18)
The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Ape1/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Ape1 can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Ape1 redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Ape1. Benzoquinone and naphthoquinone analogues of the Ape1-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Ape1 redox activity, and the most potent analogues inhibited tumor cell growth with IC50 values in the 10-20 μM range.
