WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201436
Description: GPI-15427 is a potent PARP-1 inhibitor capable of crossing the blood-brain barrier, which can significantly increased the antitumor activity of the methylating agent TMZ against malignant melanoma, glioblastoma multiforme, or lymphoma growing at the CNS site. GPI-15427 acts as a potent inhibitor of the enzyme, being capable of inhibiting the activity of purified PARP-1 at nanomolar concentrations. GPI-15427 induced significant sensitization to radiotherapy, representing a promising new treatment in the management of HNSCC.
MedKoo Cat#: 201436
Chemical Formula: C20H20N4O2
Exact Mass: 348.15863
Molecular Weight: 348.4
Elemental Analysis: C, 68.95; H, 5.79; N, 16.08; O, 9.18
Synonym: GPI15427; GPI 15427; GPI-15427.
IUPAC/Chemical Name: 10-((4-methylpiperazin-1-yl)methyl)chromeno[4,3,2-de]phthalazin-3(2H)-one.
InChi Key: DZRLVSOGARUEGQ-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H20N4O2/c1-23-7-9-24(10-8-23)12-13-5-6-16-15(11-13)19-18-14(20(25)22-21-19)3-2-4-17(18)26-16/h2-6,11H,7-10,12H2,1H3,(H,22,25)
SMILES Code: O=C1NN=C2C3=C1C=CC=C3OC4=C2C=C(CN5CCN(C)CC5)C=C4
GPI 15427 + radiation significantly reduced tumor volume compared to vehicle treated mice and mice treated with GPI 15427 alone or mice treated with radiation alone. In conclusion, these data indicate that iv administration of the PARP inhibitor GPI 15427 is well tolerated and induces significant enhancement of radiation anti-tumor efficacy against human head and neck cancer. (source: http://aacrmeetingabstracts.org/cgi/content/abstract/2004/1/311-c).
1: Khan K, Araki K, Wang D, Li G, Li X, Zhang J, Xu W, Hoover RK, Lauter S, O'Malley B Jr, Lapidus RG, Li D. Head and neck cancer radiosensitization by the novel poly(ADP-ribose) polymerase inhibitor GPI-15427. Head Neck. 2010 Mar;32(3):381-91. doi: 10.1002/hed.21195. PubMed PMID: 19672867.
2: Di Paola R, Mazzon E, Xu W, Genovese T, Ferrraris D, MuiÃ C, Crisafulli C, Zhang J, Cuzzocrea S. Treatment with PARP-1 inhibitors, GPI 15427 or GPI 16539, ameliorates intestinal damage in rat models of colitis and shock. Eur J Pharmacol. 2005 Dec 19;527(1-3):163-71. Epub 2005 Nov 28. PubMed PMID: 16310767.
3: Tentori L, Leonetti C, Scarsella M, Vergati M, Xu W, Calvin D, Morgan L, Tang Z, Woznizk K, Alemu C, Hoover R, Lapidus R, Zhang J, Graziani G. Brain distribution and efficacy as chemosensitizer of an oral formulation of PARP-1 inhibitor GPI 15427 in experimental models of CNS tumors. Int J Oncol. 2005 Feb;26(2):415-22. PubMed PMID: 15645126.
4: Tentori L, Leonetti C, Scarsella M, D'Amati G, Vergati M, Portarena I, Xu W, Kalish V, Zupi G, Zhang J, Graziani G. Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin Cancer Res. 2003 Nov 1;9(14):5370-9. PubMed PMID: 14614022.