Antitumor agent-81

立即咨询

Antitumor agent-81

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

2765180-17-2

Antitumor agent-81 (化合物 5 a) 是一种低细胞毒性的P62-RNF168激动剂，能促进P62与RNF168的相互作用。Antitumor agent-81 诱导RNF168介导的H2A泛素化减少，并损害同源重组介导的 DNA 修复。Antitumor agent-81 还能以剂量依赖的方式抑制小鼠异种移植肿瘤的生长。

生物活性

Antitumor agent-81 (compound 5a) is a low cytotoxicP62-RNF168agonist that promotes the interaction ofP62withRNF168. Antitumor agent-81 induces a decrease inRNF168-mediatedH2Aubiquitination and impairs homologous recombination-mediated DNA repair. Antitumor agent-81 also inhibits mice xenograft tumor growth in a dose-dependent manner^[1].

体外研究
(In Vitro)

Antitumor agent-81 (0-20 μM; 72 h) exhibits antiproliferative activity in cells of the most common cancer types^[1].
Antitumor agent-81 (1, 2, 5 μM; 24 h) compromises HR (homologous recombination)-mediated DSB repair in HCT-116 cells^[1].
Antitumor agent-81 tethers the interaction between P62 and RNF168 in HCT-116 cells^[1].
Antitumor agent-81 inhibits the catalytic activity of RNF168 and RNF168 E3 ligase activity in HCT-116 cells^[1].

Cell Proliferation Assay^[1]

Cell Line:	A549, HCT-116, A375, HeLa, HepG2, MCF-7, MDA-MB-231, MGC-803, U2OS and MCF-10A cells
Concentration:	0-20 μM
Incubation Time:	72 h
Result:	Inhibited A549, HCT-116, A375, HeLa, HepG2, MCF-7, MDA-MB-231, MGC-803, U2OS and MCF-10A cells, with IC₅₀values of 1.18, 0.36, 1.93, 2.48, 19.61, 2.79, 1.17, 1.88, 3.64 and 6.98, respectively.

Cell Cycle Analysis^[1]

Cell Line:	HCT-116 cells
Concentration:	1, 2, 5 μM
Incubation Time:	24 h
Result:	Induced a G2/M arrest but no significant accumulation of sub-G1 phase. Compromised both HR(homologous recombination)- and NHEJ (non-homologous end joining)- mediated DSB repair in a dose-dependent manner, but HR was the more severely impacted process.

体内研究
(In Vivo)

Antitumor agent-81 (5, 10 mg/kg; i.p.; single every 3 days for 22 days) suppresses tumor volumes in a dose-dependent manner in mice^[1].
1.19Pharmacokinetic Parameters of Antitumor agent-81 in Female BALB/c nude mice^[1].

Dose	T_1/2(h)	C_max(ng/mL)	AUC_0-t(h?ng/mL)	CL ((mL/h)/kg)
IP (5 mg/kg)	16.17	26.10	215.69	19647.83
IP (10 mg/kg)	31.00	39.87	408.18	16554.30
IP (20 mg/kg)	22.10	52.23	1003.58	14669.81

Animal Model:	Female BALB/c nude mice (xenograft tumor model)^[1].
Dosage:	5, 10 mg/kg
Administration:	Intraperitoneal injection; single every 3 days for 22 days
Result:	Suppressed tumor growth by promoting apoptosis in xenografted tumorigenesis.

Animal Model:	Female BALB/c nude mice^[1].
Dosage:	5, 10, 20 mg/kg
Administration:	Intraperitoneal injection; single
Result:	Exhibited plasma concentration peaked 1 h after administration. Showed a relatively high maximum concentration (C_max= 52.23 ng/mL) and exposure (AUC_0-t= 1003.58 hong/mL) at a dose of 20 mg/kg.

分子量

393.40

Formula

C₁₉H₁₉N₇O₃

CAS 号

2765180-17-2

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.