E7449

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

E7449 (2X-121) 是一种有效的、口服生物可利用的、脑可渗透的 PARP1/2 和 TNKS1/2 双重抑制剂，IC50 为 2.0/1.0 nM (PARP1/2)、50-100 nM (TNKS1/2)。

E7449 (2X-121) is a potent, orally bioavailable, brain penetrable dual inhibitor of PARP1/2 and TNKS1/2 with IC50 of 2.0/1.0 nM (PARP1/2), 50-100 nM (TNKS1/2); displays no significant inhibitory activity for PARP3 or PARPs6-16; shows sensitivity to cells deficient in DNA repair pathways beyond homologous recombination, inhibits Wnt/β-catenin signaling in colon cancer cell lines, stabilizes axin and TNKS proteins resulting in β-catenin de-stabilization and significantly alters expression of Wnt target genes; potentiates antitumor activity of chemotherapies temozolomide and carboplatin both in vitro and in vivo.Breast Cancer Phase 2 Clinical(In Vitro):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. (In Vivo):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).

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.

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).

E-7449 | 2X-121

Cell Cycle/DNA Damage

PARP

PARP

Cancer

Breast Cancer

1140964-99-3

317.3446

C18H15N5O

>98% (HPLC)

DMSO: < 6.96 mg/mL

O=C1NN=C(N2)C3=C(C=CC=C31)N=C2CN(C4)CC5=C4C=CC=C5

3H-Pyridazino[3,4,5-de]quinazolin-3-one, 8-[(1,3-dihydro-2H-isoindol-2-yl)methyl]-1,2-dihydro-

(-20℃)

With Ice Pack

≥ 2 years