CYP4Z1-IN-1

CYP4Z1-IN-1 (compound 7c) is a potent CYP4Z1 inhibitor, with an IC50 of 41.8 nM. CYP4Z1-IN-1 decreases the expression of breast CSCs stemness markers, spheroid formation, and metastatic ability as well as tumor-initiation capability in a concentration-dependent manner in vitro and in vivo[1].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Cytochrome P450

CYP4Z1:41.8 ± 1.4 nM (IC50)

CYP4F11:291.3 ± 46 nM (IC50)

CYP4F12:1598.3 ± 5 nM (IC50)

CYP2D6:>10 000 nM (IC50)

CYP2C9:>10 000 nM (IC50)

CYP3A4:>10 000 nM (IC50)

CYP4Z1-IN-1 (compound 7c) 显示出对乳腺 CSC (癌症干细胞)的抗增殖活性，IC50 为 483 ± 2.5 nM[1] 。 CYP4Z1-IN-1 (0.8-51.2 μM, 24 h) 抑制乳腺癌细胞中干细胞标记物 (P-gp, Oct3/4, Nanog, ALDH1A1, 和 Sox2) 的表达[1]。 CYP4Z1-IN-1 (0.8-51.2 μM, 24-48 h) 可减弱乳腺癌细胞的迁移和侵袭能力[1]。 Western Blot Analysis[1] Cell Line: MCF-7 and MDA-MB-231 cells Concentration: 0.8 μM, 3.2 μM, 12.8 μM, 51.2 μM Incubation Time: 24 h Result: Significantly suppressed the protein expression of stemness markers (P-gp, Oct3/4, Nanog, ALDH1A1, and Sox2) in MCF-7 cells in a concentration-dependent manner.

CYP4Z1-IN-1 (compound 7c) (2000 mg/kg，口服，连续 7 天)对小鼠没有明显的毒性和体重减轻[1]。 CYP4Z1-IN-1 (12.8 μM, 72 h处理MCF-7 and MDA-MB-231 cells，然后细胞皮下植入小鼠腹股沟乳腺) 可阻断乳腺癌细胞的肿瘤启动能力[1]。 Animal Model: Mice[1] Dosage: 2000 mg/kg Administration: orally, for 7 days Result: Showed that compound 7c was rather safe; no evident toxicity and body weight loss were observed. Animal Model: BALB/c-nude mice (3-4 week old, female)[1] Dosage: 12.8 μM Administration: MCF-7 and MDA-MB-231 cells were pre-treated with 7c (12.8 μM) for 72 h and were then implanted in the inguinal mammary gland of mice subcutaneously Result: Blocked the tumor-initiating ability of breast cancer cells.

[1]. Yuan Y, et al. Identification of a Novel Potent CYP4Z1 Inhibitor Attenuating the Stemness of Breast Cancer Cells through Lead Optimization. J Med Chem. 2022 Dec 8;65(23):15749-15769.