(-)-棉子素

(-)-棉子素用途

(R)-(-)-Gossypol (AT-101) 是天然产物 Gossypol 的左旋异构体。(R)-(-)-Gossypol (AT-101) 结合到 Bcl-2,Mcl-1 和 Bcl-xL 蛋白,Ki 值分别为 260±30 nM,170±10 nM 和 480±40 nM。

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(-)-棉子素名称

[ CAS 号 ]:
90141-22-3

[ 中文名 ]:
(-)-棉子素

[ 英文名 ]:
AT-101

[英文别名 ]:

UNII:XNA7DR63CQ
UNII:8DY2X8LXW4
Gossypol
UNII:KAV15B369O
AT-101

(-)-棉子素生物活性

[ 描述 ]:

(R)-(-)-Gossypol (AT-101) 是天然产物 Gossypol 的左旋异构体。(R)-(-)-Gossypol (AT-101) 结合到 Bcl-2,Mcl-1 和 Bcl-xL 蛋白,Ki 值分别为 260±30 nM,170±10 nM 和 480±40 nM。

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

信号通路 >> 细胞凋亡 >> Bcl-2家族

研究领域 >> 癌症

天然产物 >> 酚类

[ 靶点 ]

Bcl-2:260 nM (Ki)

Bcl-xL:480 nM (Ki)

Mcl-1:170 nM (Ki)

Autophagy

[体外研究]

天然外消旋棉酚具有两种对映体,即(R)-(-)-棉酚(AT-101)和(+)-棉酚对映体。 (R)-(-)-棉酚(AT-101)和(+)-棉酚与具有相似结合亲和力的Bcl-2或Bcl-xL结合,AT-101比(+)-棉酚抑制细胞更有效。生长和诱导细胞凋亡,可能是由于血清在细胞培养实验中的影响。在6天MTT测定中,针对UM-SCC-6和UM-SCC-14A测试外消旋形式和棉酚的每种对映体。在测试的两种细胞系中,相对于(±)-棉酚,AT-101表现出比(+)-棉酚更大的生长抑制(P <0.001)。用(±)-棉酚观察到中间生长抑制作用,但这种作用仅在较高剂量的棉酚(10μM,P <0.0001)下观察到。 (R)-(-)-棉酚(AT-101)以相当高的亲和力结合Bcl-xL和Bcl-2蛋白的BH3结合沟,对头颈部鳞状细胞癌(HNSCC)细胞系具有强大的活性。体外。此外,它在表达功能性p53的HNSCC肿瘤细胞中高效诱导细胞凋亡,并且还通过不同的机制杀死具有突变体p53的肿瘤细胞。抑制人成纤维细胞系生长50％所需的AT-101剂量比HNSCC细胞系高2至10倍。为了抑制人口腔角质形成细胞生长50％,(R)-(-)-棉酚(AT-101)浓度比HNSCC细胞系高2至3倍。 (R)-(-)-棉酚(AT-101)在6天MTT测定中引起10种UM-SCC细胞系中细胞生长的剂量依赖性抑制,范围为0.5至10μM。细胞系的相对敏感性不同于IC50为2-5μM的非常敏感组和IC50聚集在10μM左右的敏感性较低的组[1]。 (R)-(-)-棉酚(AT-101)被确定与Bcl-2,Mcl-1和Bcl-xL蛋白结合,Ki值为260±30 nM,170±10 nM和480±40 nM分别为[2]。

[细胞实验]

两个代表性的UM-SCC细胞系UM-SCC-6和UM-SCC-14A连续暴露于0（载体对照），5或10μM（±） - 棉酚，（R） - （ - ） - 棉酚或（+） - 在6天MTT细胞存活试验中的棉酚[1]。

[参考文献]

[1]. Oliver CL, et al. In vitro effects of the BH3 mimetic, (-)-Gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res. 2004 Nov 15;10(22):7757-63.

[2]. Sun Y, et al. Apogossypolone, a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins, effectively inhibits growth of diffuse large cell lymphoma cells in vitro and in vivo. Cancer Biol Ther. 2008 Sep;7(9):1418-26.

[相关活性小分子]

(-)-棉子素物理化学性质

[ 密度 ]:
1.4±0.1 g/cm3

[ 沸点 ]:
707.9±55.0 °C at 760 mmHg

[ 熔点 ]:
166-167ºC

[ 分子式 ]:
C₃₀H₃₀O₈

[ 分子量 ]:
518.554

[ 闪点 ]:
395.9±28.0 °C

[ 精确质量 ]:
518.194092

[ PSA ]:
155.52000

[ LogP ]:
6.16

[ 蒸汽压 ]:
0.0±2.3 mmHg at 25°C

[ 折射率 ]:
1.742

(-)-棉子素MSDS

详细MSDS(安全技术说明书)

(-)-棉子素毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DU3103500

CHEMICAL NAME :: (2,2'-Binaphthalene)-8,8'-dicarboxaldehyde, 1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl- 5,5'-bis(1-methylethyl)-, (-)-

CAS REGISTRY NUMBER :: 90141-22-3

BEILSTEIN REFERENCE NO. :: 1917878

LAST UPDATED :: 199612

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C30-H30-O8

MOLECULAR WEIGHT :: 518.60

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 210 mg/kg

SEX/DURATION :: male 2 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

REFERENCE :: JOETD7 Journal of Ethnopharmacology. (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1979- Volume(issue)/page/year: 20,21,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 320 mg/kg

SEX/DURATION :: male 40 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 31,141,1985

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(-)-棉子素安全信息

[ 危险品运输编码 ]:
NONH for all modes of transport

(-)-棉子素文献

Male contraception: history and development.

Urol. Clin. North Am. 41(1) , 145-61, (2014)

Although the twentieth century has seen great strides in the development of female contraception, not a single new agent has been introduced as an approved method for common use for male contraception...

The investigational agent MLN2238 induces apoptosis and is cytotoxic to CLL cells in vitro, as a single agent and in combination with other drugs.

Br. J. Haematol. 165(1) , 78-88, (2014)

Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in the U.S. The course of the disease has been shown to be negatively impacted by increased levels of BCL2. Strategies ...

(-)-Gossypol-enriched cottonseed oil inhibits proliferation and adipogenesis of human breast pre-adipocytes.

Anticancer Res. 33(3) , 949-55, (2013)

Breast cancer is the most commonly diagnosed cancer in women. Obesity is an important risk factor for developing breast cancer and is one of few risk factors that women can modify to prevent cancer. (...

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