505487

TEPP-46

≥98% (HPLC), solid, PKM2 activator, Calbiochem^®

• Synonyme(s) : PKM2 Activator IV, TEPP-46, 6-((3-Aminophenyl)methyl)-4-methyl-2-methylsulfinylthieno[3,4]pyrrolo[1,3-d]pyridazin-5-one, Pyruvate Kinase M2 Activator IV, ML265, NCGC00186528, TEPP46, Pyruvate Kinase M2 Activator IV, ML265, NCGC00186528, TEPP46, 6-((3-Aminophenyl)methyl)-4-methyl-2-methylsulfinylthieno[3,4]pyrrolo[1,3-d]pyridazin-5-one
• Formule empirique (notation de Hill): C₁₇H₁₆N₄O₂S₂
• Numéro CAS: 1221186-53-3
• Poids moléculaire : 372.46
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• product name: PKM2 Activator IV, TEPP-46,
• Pureté: ≥98% (HPLC)
• Niveau de qualité: 100
• Forme: solid
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: white
• Solubilité: DMSO: 100 mg/mL
• Conditions d'expédition: ambient
• Température de stockage: 2-8°C
• InChI: 1S/C17H16N4O2S2/c1-20-13-7-14(25(2)23)24-16(13)12-8-19-21(17(22)15(12)20)9-10-4-3-5-11(18)6-10/h3-8H,9,18H2,1-2H3
• Clé InChI: ZWKJWVSEDISQIS-UHFFFAOYSA-N

Description

Description générale

A cell-permeable thienopyrrolopyridazinone that acts as a potent allosteric PKM2 activator (AC₅₀ = 92 nM; [PKM2] = 0.1 nM) via stoichiometric interaction (Two activator molecules per tetramer) with FBP-bound PKM2 tetramer (One FBP per monomer) in a similar manner as PKM2 Activator III (Cat. No. 504537), resulting in highly stabilized PKM2 tetramer resistant to dissociation in the presence of phosphotyrosine-containing peptide/protein or upon PKM2 K305Q mutation. Reported to exhibit good aqueous solubility (29.6 µg/mL or 79.5 µM in PBS, pH 7.4) and retard human lung carcinoma H1299 proliferation under hypoxia, but not normoxia, condition in cultures (doubling time = 50 and 35 h, respectively, with or without 30 µM TEPP-46; 1% O₂) in vitro. TEPP-46 is bioavailable in mice via i.p. (T_max = 0.5 h; C_max = 10.854 µg/mL; AUC_INF = 26.994 hr·µg/mL; 10 mg/kg) or p.o. (T_max = 0.25 h; C_max = 10.179 µg/mL; AUC_INF = 24.350 hr·µg/mL; 10 mg/kg) administration and shown to impair H1299 tumorigenesis in mice (%tumor development/av. tumor weight = 30%/0.13 mg and 70%/2.6 mg, respectively, with or without 50 mg/kg/12 h oral dosage for 7 wks) in vivo with no apparent toxicity.

A cell-permeable thienopyrrolopyridazinone that exhibits good aqueous solubility (29.6 µg/mL or 79.5 µM in PBS, pH 7.4) and acts as a potent allosteric PKM2 activator (AC₅₀ = 92 nM; [PKM2] = 0.1 nM) by stabilizing PKM2 tetramer via stoichiometric interaction with FBP-bound PKM2 (2 activator/4 FBP/tetramer) in a similar manner as PKM2 Activator III (Cat. No. 504537). Reprorted to retard human lung carcinoma H1299 proliferation under hypoxia, but not normoxia, condition in cultures (doubling time = 50 and 35 h, respectively, with or without 30 µM TEPP-46; 1% O₂) in vitro and impair H1299 tumorigenesis in mice (50 mg/kg/12 h p.o.) in vivo with no apparent toxicity.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
PKM2

Reversible: yes

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.

Use only fresh DMSO for reconstitution.

Autres remarques

Anastasiou, D., et al. 2012. Nat. Chem. Biol.8, 839.

Jiang, J.K., et al. 2010. Bioorg. Med. Chem. Lett.20, 3387.

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 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable