475949

NMS-P715

≥98% (HPLC), powder, MPS1 inhibitor, Calbiochem^®

• Synonyme(s) : MPS1 Inhibitor, NMS-P715, (N-(2,6-diethylphenyl)-1-methyl-8-({4-[(1-methylpiperidin-4-yl)carbamoyl]-2-(trifluoromethoxy)phenyl}amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide)
• Formule empirique (notation de Hill): C₃₅H₃₉F₃N₈O₃
• Numéro CAS: 1202055-32-0
• Poids moléculaire : 676.73
• Numéro MDL: MFCD19443684
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• product name: MPS1 Inhibitor, NMS-P715, The MPS1 Inhibitor, NMS-P715 controls the biological activity of MPS1. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications.
• Niveau de qualité: 100
• Pureté: ≥98% (HPLC)
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: white
• Solubilité: DMSO: 10 mg/mL, clear, colorless
• Conditions d'expédition: ambient
• Température de stockage: 2-8°C
• Chaîne SMILES: CN(N=C1C(NC2=C(CC)C=CC=C2CC)=O)C3=C1CCC4=C3N=C(NC5=CC=C(C(NC6CCN(C)CC6)=O)C=C5OC(F)(F)F)N=C4

Description

Description générale

An orally bioavailable, ATP-competitive, pyrazolo-quinazoline, MPS1 inhibitor (IC₅₀ = 182 nM, K_i = 0.99 nM) that is shown to act in a reversible and time-dependent manner. It demonstrates selectivity for MPS1 against a panel of 60 kinases, displaying activity against only three kinases, CK2, MELK, and NEK6 (<10 M), but not against other mitotic kinases including PLK1, CDK1, Aurora A, Aurora B, or the SAC kinase BUB1, in an in vitro kinase assay. It promotes massive SAC (spindle assembly checkpoint) override (EC₅₀ = 65 nM) in nocodazole-arrested U20S cells and elicits a reduction in the G1 and G2/M phase of the cell cycle in A2780 ovarian cancer cells, similar to RNAi-mediated MPS1 silencing. In addition, it is shown to inactivate SAC, delocalize kinetochore components, and inhibit the proliferation of select cancer cell lines (IC₅₀ ~ 1 M), without marked activity among a panel of 127 normal cell lines. Also, it inhibits A2780 tumor xenograft growth in mice (90 mg/kg/day, o.s., in vivo) by 53% without marked body weight loss. Also available as a 5 mM solution in DMSO (Cat. No. 506313).

An orally bioavailable, ATP-competitive, pyrazolo-quinazoline, MPS1 inhibitor (IC₅₀ = 182 nM, K_i = 0.99 nM) that is shown to act in a reversible and time-dependent manner. It demonstrates selectivity for MPS1 against a panel of 60 kinases, displaying activity against only three kinases, CK2, MELK, and NEK6 (<10 µM), but not against other mitotic kinases including PLK1, CDK1, Aurora A, Aurora B, or the SAC kinase BUB1, in an in vitro kinase assay. It promotes massive SAC (spindle assembly checkpoint) override (EC₅₀ = 65 nM) in nocodazole-arrested U20S cells and elicits a reduction in the G1 and G2/M phase of the cell cycle in A2780 ovarian cancer cells, similar to RNAi-mediated MPS1 silencing. In addition, it is shown to inactivate SAC, delocalize kinetochore components, and inhibit the proliferation of select cancer cell lines (IC₅₀ ~ 1 µM), without marked activity among a panel of 127 normal cell lines. Also, it inhibits A2780 tumor xenograft growth in mice (90 mg/kg/day, o.s., in vivo) by 53% without marked body weight loss.

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

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

Autres remarques

Caldarelli, M., et al. 2011. Bioorg. Med. Chem. Lett.21, 4507.
Colombo, R., et al. 2011. Cancer Res.70, 10255.

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 2
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable