XL413 hydrochloride

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

XL-413 是一种口服生物可利用的细胞分裂周期 7 同系物 (CDC7) 激酶抑制剂，具有潜在的抗肿瘤活性。

XL-413 is an orally bioavailable cell division cycle 7 homolog (CDC7) kinase inhibitor with potential antineoplastic activity. CDC7 kinase inhibitor BMS-863233 binds to and inhibits the activity of CDC7, which may result in the inhibition of DNA replication and mitosis, the induction of tumor cell apoptosis, and the inhibition of tumor cell proliferation in CDC7-overexpressing tumor cells. CDC7, a serine-threonine kinase overexpressed in a variety of tumor cell types, plays an essential role in the initiation of DNA replication by activating origins of replication.(In Vitro):XL413 (BMS-863233) hydrochloride inhibits the cell proliferation (IC50=2685 nM), decreases cell viability (IC50=2142 nM) and elicits the caspase 3/7 activity (EC50=2288 nM) in Colo-205 cells. XL413 hydrochloride also significantly inhibits the anchorage-independent growth of colo-205 in soft agar (IC50=715 nM).XL413 hydrochloride shows cytotoxic effects on tumors, with IC50 of 22.9 μM in HCC1954 cells and 1.1 μM in Colo-205 cells. XL413 hydrochloride induces apoptosis in the Colo-205 cells, but not in HCC1954 cells. XL413 is effective DDK inhibitors in vitro, with IC50 of 22.7 nM. XL413 hydrochloride is defective in inhibiting DDK-dependent Mcm2 phosphorylation in HCC1954 cells but is effective in Colo-205 cells.(In Vivo):XL413 (BMS-863233; 100 mg/kg, p.o.) hydrochloride shows excellent plasma exposures in mice and possesses good PK properties. XL413 (10, 30, or 100 mg/kg, p.o.) hydrochloride is well tolerated at all the doses, with no significant body weight loss.

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PI3K/Akt/mTOR signaling

mTOR

CK2| Cdc7| Pim1

Cancer

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1169562-71-3

326.18

C14H13Cl2N3O2

>98% (HPLC)

DMSO : 3.4 mg/mL

c1([nH]c2c(c(=O)n1)oc1c2cc(cc1)Cl)[C@H]1NCCC1.Cl

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(-20℃)

With Ice Pack

≥ 2 years