Deguelin

	参数	值	评价
结构信息
		氢键受体数	6	Excellent
		可旋转键的数量	2	Excellent
		环数	5	Excellent
		最大环中的原子数	22	―
		杂原子数	6	Excellent
稳定性
		刚性键数	27	Excellent
		柔性	0.074	―
		立体中心数	2	Excellent
溶解性
		拓扑极性表面积	63.22	Excellent
		水溶性值的对数	-4.590 log mol/L	―
		正辛醇/水分配系数的对数	4.573 log mol/L	―
		pH=7.4时正辛醇/水分布系数的对数	4.055 log mol/L	―
药代动力学参数
		定量评估药物相似性	0.767	Excellent
		合成可行性分数	3.698	Excellent
		化合物和天然产物在化学空间中的接近度评分	2.264	―
		类药五原则	Accepted	Accepted
		葛兰素史克内使用的成分 ADMET 分析规则	Rejected	Rejected
		Golden Triangle	Accepted	Accepted
吸收
		人结肠癌的Caco-2细胞渗透性	-4.906	Excellent
		Madin-Darby 犬肾细胞渗透性	0.0000322141 cm/s	Excellent
		Pgp抑制剂	0.999	Poor
		Pgp底物	0	Excellent
		人体肠道吸收性	0.006	Excellent
		人体口服生物利用度20%	0.008	Excellent
分布
		血浆蛋白结合率	0.9827	―
		体积分布	0.74	Excellent
		血脑屏障通透性	0.115	Excellent
		血浆中未结合的部分	0.054	Medium
代谢
		CYP 1A2 抑制剂	0.297	―
		CYP 2C19 抑制剂	0.897	―
		CYP 2C9 抑制剂	0.882	―
		CYP 2D6 抑制剂	0.937	―
		CYP 3A4 抑制剂	0.949	―
		CYP 1A2 底物	0.858	―
		CYP 2C19 底物	0.851	―
		CYP 2C9 底物	0.902	―
		CYP 2D6 底物	0.849	―
		CYP 3A4 底物	0.646	―
排泄
		药物的清除	5.186	Medium
		药物的半衰期	0.093	Excellent
毒性参数
		Pfizer Rule	Rejected	Rejected
		SR-MMP	0.888	―
致毒剂量
		FDA 推荐的每日最大剂量	0.847	Poor
		IGC50	4.826	―
		LC50FM	7.251	―
		LC50DM	7.069	―
致畸性
		NR-AR(Androgen receptor)	0.016	Excellent
		NR-AR-LBD(Androgen receptor)	0.143	Excellent
		NR-Aromatase	0.847	Poor
		NR-ER(Estrogen receptor)	0.376	Medium
		NR-ER-LBD(Estrogen receptor)	0.759	Poor
致敏性
		皮肤致敏规则	3	―
		皮肤致敏	0.167	Excellent
急性毒性
急性毒性		大鼠经口急性毒性	0.696	Medium
器官毒性
		hERG 阻滞剂	0.11	Excellent
		人体肝毒性	0.842	Poor
		药物性肝损伤	0.735	Poor
直接刺激性
		眼睛刺激性	0.003	Excellent
		眼睛腐蚀性	0.04	Excellent
		呼吸道毒性	0.857	Poor
致突变性
致突变性		污染物致突变性	0.222	Excellent
致肿瘤性
		致癌性	0.767	Poor
		抗氧化反应元件	0.819	Poor
		ATP酶家族含AAA结构域蛋白5	0.805	Poor
		SR-p53	0.959	Poor

中药材名称	中药材拉丁名	性	味	归经
灰叶根	Tephrosia purpurea(L.)Pers.	凉	微苦	脾, 胃
铃兰	Convallaria keiskei Miq.	温	甘, 苦
毛鱼藤	Derris elliptica (Roxb.) Benth.	-	―
木榄	Bruguiera gymnorhiza (Linnaeus) Savigny	平	涩	大肠
鱼藤	Derris trifoliata	温	苦, 辛	肝

中药材名称

中药材拉丁名

性

味

归经

灰叶根

Tephrosia purpurea(L.)Pers.

凉

微苦

脾, 胃

铃兰

Convallaria keiskei Miq.

温

甘, 苦

毛鱼藤

Derris elliptica (Roxb.) Benth.

―

木榄

Bruguiera gymnorhiza (Linnaeus) Savigny

平

涩

大肠

鱼藤

Derris trifoliata

温

苦, 辛

肝

产品描述	Deguelin is a PI3K/AKT Inhibitor, which is a natural product isolated from plants in the Mundulea sericea family.
体外活性	In leukaemia cell lines, Deguelin downregulates Akt phosphorylation through activating PI3K/Akt axis. Deguelin increases the sensitivity of human leukaemia cells to chemotherapeutic drugs. In U937 cells deguelin does not affect the expression or the phosphorylation levels of either p44/42 or p38 MAP kinases. Deguelin, when employed for 24 h at 10 nmol/l, causes an S phase arrest of U937 cells, with interference of progression to G2/M phase. While employed alone up to a concentration of 10 nmol/l for 24 h, Deguelin does not significantly increase the apoptotic rate of U937 cells.Deguelin （10 or 100 nmol/l） is potent in inhibiting Akt phosphorylation,while deguelin does not affect total Akt expression. Deguelin dephosphorylates Akt and increases cytarabine sensitivity of AML blasts but not of CB CD34+.
体内活性	In pre-clinical trials, deguelin markedly decreased the tumor incidence. It exhibited significant anti-tumorigenesis and anti-proliferative activity in various types of cancer both in vitro and in vivo. Topically-administered deguelin significantly suppressed the multiplicity of skin tumors with UVB-induction, indicating its effect as a potential cancer chemopreventive agent. Treatment with deguelin, a potential mitochondria complex I inhibitor, reduced tyrosine hydroxylase-positive neurons, leading to Parkinson's disease.Deguelin promoted a PD-like syndrome, mainly by Src/STAT signaling, since α-synuclein (a key protein function in the pathogenesis of PD) was phosphorylated by deguelin-activated Src.Deguelin inhibits in vivo angiogenesis of chick chorioallantoic membrane (CAM) without cytotoxic effect and significantly reduces laser-induced CNV in a mouse model of AMD without significant retinal toxicity. In A/J mice, deguelin clearly reduced the tumor multiplicity and volume, as well as the overall tumor burden with exposure to the tobacco-specific carcinogen benzo(a)pyrene (Bap) and other carcinogens, with no detectable toxicity.
激酶实验	Caspase 3 activity is determined using Caspase-Glo-3 assays. This assay provides luminogenic substrate in a buffer system optimized for each specific caspase activity. The caspase cleavage of the substrate is followed by generation of a luminescent signal. The signal generated is proportional to the amount of caspase activity present in the sample. Protein (10 μg) from the cell samples is diluted in water to a final volume of 50 μL and added to a white 96-well microtitre plate, followed by 50 μL of Caspase-Glo-3 reagent. The plate is sealed and gently mixed at 300-500 rpm for 30 s and incubated at room temperature for 30 min. Luminescence is measured in a microplate reader (TECAN Infinite 200).
细胞实验	U937 Cells are incubated with the indicated concentrations (1 nM, 10 nM, 100 nM) of deguelin for 24 h.Flow cytometric analysis of cell cycle in response to deguelin. Flow cytometric analysis of cell cycle in response to deguelin.
动物实验	A/J mice were treated by oral gavage of 5.0 or 10.0 mg/kg deguelin dissolved in corn oil.

别名	(-)-cis-Deguelin, 鱼藤素, (-)-Deguelin, 魚藤素
分子量	394.42
分子式	C23H22O6
CAS No.	522-17-8

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溶解度

产品理化性质

中药材来源及性味归经

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