5.33850

TAM Receptor Kinase Inhibitor, LDC1267

• Synonyme(s) : TAM Receptor Kinase Inhibitor, LDC1267, TAM Receptor Blocker
• Formule empirique (notation de Hill): C₃₀H₂₆F₂N₄O₅
• Numéro CAS: 1361030-48-9
• Poids moléculaire : 560.55
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• 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: 50 mg/mL
• Température de stockage: 2-8°C
• InChI: 1S/C30H26F2N4O5/c1-5-40-28-16-36(23-8-6-18(31)12-17(23)2)35-29(28)30(37)34-19-7-9-25(21(32)13-19)41-24-10-11-33-22-15-27(39-4)26(38-3)14-20(22)24/h6-16H,5H2,1-4H3,(H,34,37)
• Clé InChI: ISPBCAXOSOLFME-UHFFFAOYSA-N

Description

Description générale

A cell-permeable, bioactive, non-toxic quinoline based compound that acts as a highly potent, ATP-non-competitive, tight-binding type II TAM (Tyro3, Axl, and Mer) kinase inhibitor (IC₅₀ = 8, 29, and 5 nM, respectively for Tyro3, Axl, and Mer). Occupies both the ATP binding cleft and an adjacent hydrophobic pocket. Also displays inhibitory activity against Met, Aurora B, Lck, and Src, but only at relatively higher concentration (IC₅₀ = 35, 36, 51, and 338 nM, respectively). Displays modest selectivity over 39 other protein kinases (at ~1 µM). Reduces the proliferation of selected cancer lines (~ 15 µM). By inhibiting TAM receptors, it enhances anti-metastatic activity of natural killer (NK) cells via TAMR/E3 ligase (Cbl-b; casitas B-lineage lymphoma-b) pathway modulation. Reduces the number and size of 4T1 micro metastases in the liver of an orthotopic murine model of metastatic breast cancer without apparently affecting the primary mammary tumor. Also shown to reduce metastatic spreading of B16F10 melanomas, an effect that is abolished upon NK1.1 depletion.

A cell-permeable, bioactive, non-toxic quinoline based compound that acts as a highly potent, ATP-non-competitive, tight-binding type II TAM (Tyro3, Axl, and Mer) kinase inhibitor (IC₅₀ = 8, 29, and 5 nM, respectively for Tyro3, Axl, and Mer). Occupies both the ATP binding cleft and an adjacent hydrophobic pocket. Also displays inhibitory activity against Met, Aurora B, Lck, and Src, but only at relatively higher concentration (IC₅₀ = 35, 36, 51, and 338 nM, respectively). Displays modest selectivity over 39 other protein kinases (at ~1 µM). Reduces the proliferation of selected cancer lines (~ 15 µM). By inhibiting TAM receptors, it enhances anti-metastatic activity of natural killer (NK) cells via TAMR/E3 ligase (Cbl-b; casitas B-lineage lymphoma-b) pathway modulation. Reduces the number and size of 4T1 micro metastases in the liver of an orthotopic murine model of metastatic breast cancer without apparently affecting the primary mammary tumor. Also shown to reduce metastatic spreading of B16F10 melanomas, an effect that is abolished upon NK1.1 depletion.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

TAM Receptor Kinase Inhibitor, LDC1267, is a cell-permeable, tight-binding "type II" TAM kinase inhibitor (IC₅₀ = 8, 29 & 5 nM for Tyro3, Axl & Mer). Enhances anti-metastatic activity of NK cells.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
Tyro3, Axl, and Mer kinases

Secondary Target
Met, Aurora B, Lck and Src kinases

Target IC₅₀: 8, 29, and 5 nM for Tyro3, Axl, and Mer, respectively

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

Paolino, M., et al. 2014. Nature.507, 508.

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