128125

Aloisine A

A cell-permeable pyrrolo-pyrazine compound that exerts anti-proliferative effects.

• Synonym(e): Aloisine A, RP107, 7- n-Butyl-6-(4-hydroxyphenyl)[5H]pyrrolo[2,3-b]pyrazine
• Empirische Formel (Hill-System): C₁₆H₁₇N₃O
• CAS-Nummer: 496864-16-5
• Molekulargewicht: 267.33
• MDL-Nummer: MFCD04973541
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Qualitätsniveau: 100
• Assay: ≥95% (HPLC)
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: yellow
• Löslichkeit: DMSO: 10 mg/mL
• Versandbedingung: ambient
• Lagertemp.: 2-8°C
• SMILES String: [nH]1c2nccnc2c(c1c3ccc(cc3)O)CCCC
• InChI: 1S/C16H17N3O/c1-2-3-4-13-14(11-5-7-12(20)8-6-11)19-16-15(13)17-9-10-18-16/h5-10,20H,2-4H2,1H3,(H,18,19)
• InChIKey: PRIGRJPRGZCFAS-UHFFFAOYSA-N

Beschreibung

Allgemeine Beschreibung

A cell-permeable pyrrolo-pyrazine compound that exerts anti-proliferative effects. Acts as a potent, selective, reversible, and ATP-competitive inhibitor of cyclin-dependent kinases (Cdks; IC₅₀ = 150 nM, 120 nM, 400 nM, and 200 nM for Cdk1/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E, and Cdk5/p25, respectively), glycogen synthase kinase-3 (GSK-3; IC₅₀ = 500 nM and 1.5 µM for GSK-3α, GSK-3β, respectively), and c-Jun N-terminal kinase (JNK; IC₅₀ = ~ 3 - 10 µM). It inhibits several other enzymes (CK1, CK2, MAPKK, PKA, PKG, PKCs, and c-raf) poorly (IC₅₀ ≥ 100 µM). Shown to arrest cells in both G₁ and G₂ phases (IC₅₀ = 7 µM and 10.5 µM for undifferentiated human teratocarcinoma cells NT2 and differentiated postmitotic neurons hNT, respectively). Shown to selectively stimulate CFTR-dependent iodide efflux in wtCFTR-CHO, Calu-3 and F508del-CFTR-CF15 cells in the presence of 1 µM Forskolin (Cat. No. 344270) with high affinity (EC₅₀ = 150 nM, 140 nM and 111 nM, respectively).

A cell-permeable, pyrrolo-pyrazine compound that exerts anti-proliferative effects. Acts as a potent, selective, reversible, and ATP-competitive inhibitor of cyclin-dependent kinases (Cdks; IC₅₀ = 150 nM for Cdk1/cyclin B, 120 nM for Cdk2/cyclin A, 400 nM for Cdk2/cyclin E, and 160 nM for Cdk5/p25), glycogen synthase kinase-3 (GSK-3; IC₅₀ = 500 nM for GSK-3α and 1.5 µM for GSK-3β), and c-Jun N-terminal kinase (JNK; IC₅₀ ~3-10 µM). Also inhibits extracellular signal-regulated kinases (ERKs; IC₅₀ = 18 µM for ERK1 and 22 µM for ERK2), PIM1 (IC₅₀ >10 µM), and insulin receptor tyrosine kinase (IC₅₀ = 60 µM) at higher concentrations. Does not significantly inhibit Cdk4/cyclin D1, CK1, CK2, MAPKK, PKA, PKG, PKCs, or c-raf (IC₅₀ = ≥ 100 µM). Shown to arrest undifferentiated human teratocarcinoma cells (NT2) and differentiated post-mitotic neurons (hNT) in both G₁ and G₂ phases (IC₅₀ = 7 µM and 10.5 µM, respectively). Also shown to selectively stimulate CFTR-dependent iodide efflux in wtCFTR-CHO, Calu-3 and F508del-CFTR-CF15 cells in the presence of 1 µM of Forskolin (Cat. No. 344270) with high affinity (EC50 = 150 nM, 140 nM and 111 nM, respectively).

Biochem./physiol. Wirkung

Cell permeable: yes

EC50 = 150 nM, 140 nM and 111 nM, in stimulating CFTR-dependent iodide efflux in wtCFTR-CHO, Calu-3 and F508del-CFTR-CF15 cells in the presence of 1 µM Forskolin, respectively

Primary Target
Cyclin-dependent kinases

Product competes with ATP.

Reversible: yes

Target IC₅₀: 150 nM, 120 nM, 400 nM, and 200 nM for Cdk1/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E, and Cdk5/p25, respectively; 500 nM and 1.5 µM for GSK-3α, GSK-3β, respectively

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

Following reconstitution aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Sonstige Hinweise

Noel, S., et al. 2006. J. Pharm. Exp. Ther. , 319, 349.
Mettey, Y., et al. 2003. J. Med. Chem.46, 222.

Rechtliche Hinweise

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 1
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable