565852

PTP Inhibitor XXXI, II-B08

The PTP Inhibitor XXXI, II-B08 controls the biological activity of PTP. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications.

• Synonyme(s) : PTP Inhibitor XXXI, II-B08, CD45 Inhibitor V, FAP1 Inhibitor, LMWPTP Inhibitor, Lyp Inhibitor III, PTP1B Inhibitor IX, SHP1 Inhibitor IX, SHP2 Inhibitor VI, 3-(1-(3-(Biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid
• Formule empirique (notation de Hill): C₃₃H₂₇N₅O₄
• Poids moléculaire : 557.60
• Code UNSPSC : 12352200

Propriétés

• Niveau de qualité: 200
• Pureté: ≥98% (HPLC)
• Forme: powder
• Puissance: 5.2 μM K_i
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: yellow-white
• Solubilité: DMSO: 100 mg/mL
• Conditions d'expédition: ambient
• Température de stockage: 2-8°C

Description

Description générale

A cell-permeable indolo-salicylic acid compound that is shown to target SHP2 catalytic domain and inhibit SHP2-catalyzed pNPP hydrolysis (IC₅₀ = 5.5 µM) in a reversible and non-competitive manner (K_i = 5.2 µM), exhibiting 2.6- to 5.7-fold selectivity over PTP1B, SHP1, FAP1, Lyp, CD45, and LMWPTP (IC₅₀ = 14.3, 15.7, 20.3, 25.0, 30.0, and 31.1 µM, respectively) and >9-fold selectivity over Cdc14A, HePTP, LAR, PTPα, and VHR (IC₅₀ >50 µM). Effectively blocks hyperproliferative activity of human hematopoietic progenitor cells (Effective conc. = 10 µM) due to SHP2 mutations (D61Y and E76K) or GM-CSF stimulation, as well as c-kit-dependent (via ligand stimulation or D814V mutation), SHP2-mediated myeloid proliferation (Effective conc. = 5 to 75 µM). Dual PI-3K and SHP2 inhibition by LY294002 (Cat. Nos. 440202 & 440204) and II-B08 (10 mg/kg and 50 mg/kg, respectively; daily i.p.) is shown to greatly prolong the survival rate in a D814V KIT-expressing 32D-based murine MPD (myeloproliferative disease) model (0% survival rate on day 23, 27, 28, respectively, with DMSO, LY294002, II-B08 treatment alone; 20% survival rate on day 65 with combined treatment) in vivo.

A cell-permeable indolo-salicylic acid compound that is shown to target SHP2 catalytic domain and inhibit SHP2-catalyzed pNPP hydrolysis (IC₅₀ = 5.5 µM) in a reversible and non-competitive manner (K_i = 5.2 µM), exhibiting 2.6- to 5.7-fold selectivity over PTP1B, SHP1, FAP1, Lyp, CD45, and LMWPTP (IC₅₀ = 14.3, 15.7, 20.3, 25.0, 30.0, and 31.1 µM, respectively). Effectively blocks SHP2-mediated human hematopoietic progenitor cell hyperproliferation (10 µM) due to SHP2 mutations (D61Y and E76K) or GM-CSF stimulation, as well as c-kit-dependent (due to D814V mutation or via ligand stimulation), SHP2-mediated myeloid proliferation (5 to 75 µM). Dual PI-3K and SHP2 inhibition by LY294002 (Cat. Nos. 440202 & 440204) and II-B08 (10 mg/kg and 50 mg/kg, respectively; daily i.p.) is shown to greatly prolong the survival rate of mice bearing D814V KIT-expressing 32D cells in vivo.

Actions biochimiques/physiologiques

Primary Target
SHP2

Reversible: yes

Secondary Target
Other PTPs

Target IC₅₀: 5.5, 9.0 and 10.8 &micro

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 6 months at -20°C.

Autres remarques

Mali, R.S., et al. 2012. Blood120, 2669.
Zhang, X., et al. 2010. J. Med. Chem.53, 2482.

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