product name LDC1267
Description: LDC1267 is a highly potent and selective TAM kinase inhibitor with IC50 of <5 nM, 8 nM, and 29 nM for Mer, Tyro3, and Axl, respectively. Displays lower activity against Met, Aurora B, Lck, Src, and CDK8. LDC1267 displays lower activity against Met, Aurora B, Lck, Src, and CDK8. LDC1267 markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo.
References: Nature. 2014 Mar 27;507(7493):508-12.
560.55
Formula
C30H26F2N4O5
CAS No.
1361030-48-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (178.4 mM)
Water: <1 mg/mL
Ethanol: 2 mg/mL (3.6 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: LDC1267 moderately affects cell proliferation in 11 of 95 different cell lines with IC50 of >5μM. In NKG2D-activated NK cells, LDC1267 abolishes the inhibitory effects of Gas6 stimulation. Kinase Assay: For optimization of Axl/TAM receptor inhibitors, an Axl binding assay is established (HTRF method; Kinase tracer 236). This assay is based on the binding and displacement of the Alexa Fluor 647-labelled Kinase tracer 236 to each glutathione S-transferase (GST)-tagged kinase used in the binding assay. Binding of the tracer to the kinase was detected by using europium (Eu)-labelled anti-GST antibodies. Simultaneous binding of both the fluorescent tracer and the Eu-labelled antibodies to the GST-tagged kinase generates a fluorescence resonance energy transfer (FRET) signal. Binding of inhibitor to the kinase competes for binding with the tracer, resulting in a loss of the FRET signal. For the assay, the compound is diluted in 20 mM HEPES, pH 8.0, 1 mM DTT, 10 mM MgCl2 and 0.01% Brij35. Then, the kinase of interest (5 nM final concentration), fluorescent tracer (15 nM final concentration) and LanthaScreen Eu-anti-GST antibody (2 nM final concentration) are mixed with the respective compound dilutions (from 5 nM to 10 μM) and incubated for 1 h. The FRET signal is quantified using an EnVision Multilabellreader 2104. Cell Assay: After incubation for 72 hours with LDC1267, CellTiterGlow reagent is used to determine the proliferation relative to the corresponding DMSO control. Cell lines: A panel of 93 cancer cell lines and two primary cells (x axis, IMR90 and human peripheral blood mononuclear cells). |
|---|---|
| In Vivo | In B16F10 melanoma-bearing mice, LDC1267 (20 mg/kg, i.p.) efficiently enhances anti-metastatic NK cell activity, and rejects tumor metastases without serious cytotoxicity. |
| Animal model | Mouse B16F10 metastatic melanoma model |
| Formulation & Dosage | Dissolved in 90% PEG400:10% DMSO; 20 mg/kg; i.p. |
| References | Nature. 2014 Mar 27;507(7493):508-12. |
