Stenoparib

• CAT Number: I000532
• CAS Number: 1140964-99-3
• Molecular Formula: C18H15N5O
• Molecular Weight: 317.34
• Purity: ≥95%
• Synonyms: 11-(1,3-dihydroisoindol-2-ylmethyl)-2,3,10,12-tetrazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8,11-pentaen-4-one
• InChI: InChI=1S/C18H15N5O/c24-18-13-6-3-7-14-16(13)17(21-22-18)20-15(19-14)10-23-8-11-4-1-2-5-12(11)9-23/h1-7H,8-10H2,(H,22,24)(H,19,20,21)
• InChIKey: JLFSBHQQXIAQEC-UHFFFAOYSA-N
• SMILES: C1C2=CC=CC=C2CN1CC3=NC4=NNC(=O)C5=C4C(=CC=C5)N3

Stenoparib (E7449) is a potent PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC50s of 2.0, 1.0, ∼50 and ∼50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively, using 32P-NAD+ as substrate.
Stenoparib is a potent PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC50s of 2.0, 1.0, ∼50 and ∼50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively, using 32P-NAD+ as substrate. Stenoparib shows no obvious inhibiotry effects on PARP3 or PARPs 6-16. Stenoparib traps PARP1 onto damaged DNA, and affects DNA repair pathways beyond homologous recombination (HR). Stenoparib most potnetly suppresses cells deficient in components of the HR pathway (BRCA1 and 2, CtIP, Rad54). Stenoparib (10 μM) inhibits Wnt signaling in SW480 cells[1].
Stenoparib moderately inhibits the growth of tumors at 100 mg/kg, and significantly ehhances the inhibition via 10, 30 and 100 mg/kg oral dosing in combination with temozolomide (TMZ) in the mouse melanoma B16-F10 isograft model. Stenoparib (30 or 100 mg/kg, p.o.) inhibits PARP, shows anti-tumor activity, and is well-tolerated without any obvious body weight loss or deaths in a BRCA mutant xenograft model. Stenoparib (30, 100 or 300 mg/kg, p.o.) suppresses re-growth of hair in a dose dependent manner, and blocks Wnt signaling in C57BL/6 mice. Stenoparib (100 mg/kg, p.o.) combined with MEK inhibitor exhibits antitumor activity in a Wnt1 subcutaneous model (mammary tumors initially isolated from Wnt1 (int-1) transgenic mice)[1].

Reference

[1]. McGonigle S, et al. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015 Dec 1;6(38):41307-23.
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