(-)-Indolactam V

Names

[ Name ]:
(-)-Indolactam V

[Synonym ]:
(2S,5S)-5-(hydroxymethyl)-1-methyl-2-(propan-2-yl)-1,2,4,5,6,8-hexahydro-3H-[1,4]diazonino[7,6,5-cd]indol-3-one
3H-1,4-Diazonino[7,6,5-cd]indol-3-one, 1,2,4,5,6,8-hexahydro-5-(hydroxymethyl)-1-methyl-2-(1-methylethyl)-, (2S,5S)-
(-)-indolactam
Indolactam V
(2S,5S)-5-(Hydroxymethyl)-2-isopropyl-1-methyl-1,2,4,5,6,8-hexahydro-3H-[1,4]diazonino[7,6,5-cd]indol-3-one

Biological Activity

[Description]:

(-)-Indolactam V is a PKC activator, with Kis of 3.36 nM, 1.03 μM for η-CRD2 (PKCη surrogate peptide), γ-CRD2 (PKCγ surrogate peptide), and Kds of 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), 213 nM (γ-C1B), and has antitumor activity.

[Related Catalog]:

Research Areas >> Cancer

[Target]

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)

[In Vitro]

(-)-Indolactam V is a PKC activator, with Kis of 3.36 nM, 1.03 μM for η-CRD2 (PKCη surrogate peptide), γ-CRD2 (PKCγ surrogate peptide), and has antitumor activity[1]. (-)-Indolactam V shows Kds of 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), 213 nM (γ-C1B), respectively[2]. (-)-Indolactam V (20 nM-5 μM) dose-dependently affects multiple hESC lines, such as HUES 2, 4 and 8. (-)-Indolactam V also increases the mRNA levels of Pdx1, HNF6, PTF1A, SOX9, HB9 and PROX1. In addition, (-)-Indolactam V (300 nM) functions in both mouse and human cells and confirms that some signals for pancreatic development[3].

[Cell Assay]

For induced differentiation to endocrine or exocrine cells, the (-)-Indolactam V (300 nM)-treated populations are cultured in DMEM/F12 supplemented with 1 N2, 2 mg/mL albumin fraction V and 10 ng/mL bovine FGF for the first 4 d. 10 mM nicotinamide is then added and maintained for an additional 8 d, changing the medium every 3 d[3].

[References]

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
584.0±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₇H₂₃N₃O₂

[ Molecular Weight ]:
301.383

[ Flash Point ]:
307.0±30.1 °C

[ Exact Mass ]:
301.179016

[ PSA ]:
68.36000

[ LogP ]:
0.75

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.590

MSDS

Click to get detail MSDS

Toxicological Information

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

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Articles

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...