(-)-吲哚美坦V

(-)-吲哚美坦V用途

(-)-Indolactam V 是 PKC 的激活剂,对 η-CRD2 (PKCη 代替肽),γ-CRD2 (PKCγ 代替肽) 的 Ki 值分别为 3.36 nM 和 1.03 μM,对 PKC C1A 和 C1B 结构域的 Kd 值分别为 5.5 nM (η-C1B),7.7 nM (ε-C1B),8.3 nM (δ-C1B),18.9 nM (β-C1A-long),20.8 nM (α-C1A-long),137 nM (β-C1B),138 nM (γ-C1A) 和 213 nM (γ-C1B),具有抗肿瘤活性。

(-)-吲哚美坦V名称

[ CAS 号 ]:
90365-57-4

[ 中文名 ]:
(-)-Indolactam V.

[ 英文名 ]:
(-)-Indolactam V

[英文别名 ]:

(-)-indolactam
Indolactam V

(-)-吲哚美坦V生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 癌症

[ 靶点 ]

PKCη-CRD2:3.36 nM (Ki)

PKCη-C1B:5.5 nM (Kd)

PKCε-C1B:7.7 nM (Kd)

PKCδ-C1B:8.3 nM (Kd)

PKCθ-C1B:8.7 nM (Kd)

PKCβ-C1A-long:18.9 nM (Kd)

PKCα-C1A-long:20.8 nM (Kd)

PKCβ-C1B:137 nM (Kd)

PKCγ-C1A:138 nM (Kd)

PKCγ-C1B:213 nM (Kd)

PKCγ-CRD2:1030 nM (Ki)

PKCδ-C1A:1900 nM (Kd)

PKCη-C1A:3770 nM (Kd)

PKCα-C1B-long:4000 nM (Kd)

PKCε-C1A:4110 nM (Kd)

[体外研究]

(-)- Indolactam V是PKC活化剂,Kis为3.36 nM,η-CRD2为1.03μM(PKCη替代肽),γ-CRD2(PKCγ替代肽),具有抗肿瘤活性[1]。 (-)- Indolactam V显示Kds为5.5 nM(η-C1B),7.7 nM(ε-C1B),8.3 nM(δ-C1B),18.9 nM(β-C1A-long),20.8 nM(α-C1A-长),137 nM(β-C1B),138 nM(γ-C1A),213 nM(γ-C1B),分别为[2]。 (-)- Indolactam V(20 nM-5μM)剂量依赖性地影响多种hESC系,如HUES 2,4和8.(-)- Indolactam V也增加Pdx1,HNF6,PTF1A,SOX9的mRNA水平, HB9和PROX1。此外,(-)- Indolactam V(300 nM)在小鼠和人类细胞中均有作用,并证实了胰腺发育的一些信号[3]。

[细胞实验]

为诱导分化为内分泌或外分泌细胞，（ - ） - Indolactam V（300 nM）处理的群体在补充有1 N 2，2 mg / mL白蛋白级分V和10 ng / mL牛FGF的DMEM / F12中培养。前4天然后加入10mM烟酰胺并保持另外8天，每3天更换一次培养基[3]。

[参考文献]

[1]. Nakagawa Y, et al. Synthesis and biological activities of indolactone-V, the lactone analogue of the tumor promoter (-)-indolactam-V. Biosci Biotechnol Biochem. 1997 Aug;61(8):1415-7.

[2]. Masuda A, et al. Binding selectivity of conformationally restricted analogues of (-)-indolactam-V to the C1 domains of protein kinase C isozymes. Biosci Biotechnol Biochem. 2002 Jul;66(7):1615-7.

[3]. Chen S, et al. A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol. 2009 Apr;5(4):258-65.

[相关活性小分子]

(-)-吲哚美坦V物理化学性质

[ 密度 ]:
1.2±0.1 g/cm3

[ 沸点 ]:
584.0±50.0 °C at 760 mmHg

[ 分子式 ]:
C₁₇H₂₃N₃O₂

[ 分子量 ]:
301.383

[ 闪点 ]:
307.0±30.1 °C

[ 精确质量 ]:
301.179016

[ PSA ]:
68.36000

[ LogP ]:
0.75

[ 外观性状 ]:
白色至灰白色固体

[ 蒸汽压 ]:
0.0±1.7 mmHg at 25°C

[ 折射率 ]:
1.590

[ 储存条件 ]:
-20°C，密闭，干燥

(-)-吲哚美坦VMSDS

详细MSDS(安全技术说明书)

(-)-吲哚美坦V毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UY8547000

CHEMICAL NAME :: 3H-Pyrrolo(4,3,2-gh)-1,4-benzodiazonin-3-one, 1,2,4,5,6,8-hexahydro-5-(hydroxymethyl)-1- methyl-2-(1-methylethyl)-, (2S-(2R*,5R*))-

CAS REGISTRY NUMBER :: 90365-57-4

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C17-H23-N3-O2

MOLECULAR WEIGHT :: 301.43

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1250 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 44,1029,1991

(-)-吲哚美坦V安全信息

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

(-)-吲哚美坦V文献

Structural basis of RasGRP binding to high-affinity PKC ligands.

J. Med. Chem. 45(4) , 853-60, (2002)

The Ras guanyl releasing protein RasGRP belongs to the CDC25 class of guanyl nucleotide exchange factors that regulate Ras-related GTPases. These GTPases serve as switches for the propagation and dive...

Tumor promoter binding of the protein kinase C C1 homology domain peptides of RasGRPs, chimaerins, and Unc13s.

Bioorg. Med. Chem. 12(17) , 4575-83, (2004)

Recent investigations discovered nonkinase-type phorbol ester receptors, RasGRPs, chimaerins, and Unc13s. Phorbol ester binding occurs at the cysteine-rich sequences of about 50 residues in the C1 dom...

Indolactam and benzolactam compounds as new medicinal leads with binding selectivity for C1 domains of protein kinase C isozymes.

Curr. Pharm. Des. 10(12) , 1371-85, (2004)

Protein kinase C (PKC) isozymes (alpha, betaI, betaII, gamma, delta, epsilon, eta, theta) are major receptors of tumor promoters and also play a crucial role in cellular signal transduction via the se...

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