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Product Data Sheet
Product Name:Cat. No.:
LDC1267GC14241
Chemical Properties
Cas No.ChemicalNameCanonicalSMILESFormulaSolubilityGeneraltipsShippingCondition
1361030-48-9
N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluoro-2-methylphenyl)-1H-pyrazole-3-carboxamide
FC1=CC=C(N2C=C(OCC)C(C(NC3=CC=C(OC4=CC=NC5=CC(OC)=C(OC)C=C45)C(F)=C3)=O)=N2)C(C)=C1C30H26F2N4O5
≥20.75mg/mL in DMSO
M.WtStorage
560.55Store at -20°C
For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in theultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.Evaluation sample solution : ship with blue ice All other available size: ship with RT , orblue ice upon request.
Structure
Caution: Producthasnot been fully validated for medical applications. For research use only.
Tel: (626) 353-8530 Fax: (626) 353-8530 E-mail: tech@glpbio.com
Address: 10292 Central Ave. #205, Montclair, CA, USA
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Product Data Sheet
实验参考方法
Kinase experiment [1]:
For optimization of Axl/TAM receptor inhibitors, an Axl binding assay wasestablished (HTRF method; Kinase tracer 236). This assay was based on thebinding and displacement of the Alexa Fluor 647-labelled Kinase tracer 236 toeach glutathione S-transferase (GST)-tagged kinase used in the binding assay.Binding of the tracer to the kinase was detected by using europium (Eu)-labelledanti-GST antibodies. Simultaneous binding of both the fluorescent tracer and theEu-labelled antibodies to the GST-tagged kinase generated a fluorescence
Kinase binding
resonance energy transfer (FRET) signal. Binding of inhibitor to the kinase
assays
competed for binding with the tracer, resulting in a loss of the FRET signal. Forthe assay, the compound was diluted in 20 mM HEPES, pH 8.0, 1 mM DTT, 10 mMMgCl2 and 0.01% Brij35. Then, the kinase of interest (5 nM final concentration),fluorescent tracer (15 nM final concentration) and LanthaScreen Eu-anti-GSTantibody (2 nM final concentration) were mixed with the respective compounddilutions (from 5 nM to 10 μM) and incubated for 1 hr. The FRET signal wasquantified using an EnVision Multilabellreader 2104.
Cell experiment [1]:
93 cancer cell lines and 2 primary cells (i.e. IMR90 and human peripheral blood
Cell lines
mononuclear cells)
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining ahigher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake
Preparation method
it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C forseveral months.
Reacting condition0 ~ 35 μM; 72 hrs
In 11 of 95 selected cell lines, LDC1267 moderately affected cell proliferation withthe IC50 values of > 5 μM. In NKG2D-activated NK cells, LDC1267 abolished the
Applications
inhibitory effects on cell proliferation and IFN-γ production induced by Gas6stimulation.
Animal experiment [1]:Animal modelsMice bearing B16F10 metastatic melanomasDosage form20 mg/kg; i.p.
In mice bearing B16F10 metastatic melanomas, LDC1267 efficiently increased
Applicationsanti-metastatic NK cell activity, and inhibited tumor metastases without severe
cytotoxicity.
Please test the solubility of all compounds indoor, and the actual solubility may
Other notesslightly differ with the theoretical value. This is caused by an experimental
system error and it is normal.
Caution: Producthasnot been fully validated for medical applications. For research use only.
Tel: (626) 353-8530 Fax: (626) 353-8530 E-mail: tech@glpbio.com
Address: 10292 Central Ave. #205, Montclair, CA, USA
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Product Data Sheet
References:
[1]. Paolino M, Choidas A2, Wallner S et al. The E3 ligase Cbl-b and TAM receptors regulate cancermetastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12.
Background
LDC1267 is a highly selective TAM kinase inhibitor with IC50 of < 5 nM, 8 nM, and 29 nM for Mer,Tyro3, and Axl, respectively.
LDC1267 preferentially inhibits Tyro3, Axl and Mer at low nano-molarity by tracer-based binding
assays. Treatment of NKG2D- activated NK cells with LDC1267 indeed abolished the inhibitory effectsof Gas6 stimulation; LDC1267 had no apparent additional effect in Cbl-b-deficient NK cells. Adoptivetransfer of LDC1267-treated wild-type NK cells significantly increased the anti-tumour response tolevels observed in mice transplanted with Cbl-b2/2 NK cells, but did not increase the anti-metastaticefficacy of Cbl-b-knockout NK cells, reinforcing the notion that Cbl-b acts downstream of TAMreceptors for NK cell inhibition. [1]
In vivo, wild-type mice treated with LDC1267 showed enhanced cytotoxicity towards RMA cells
overexpressing the NKG2D ligand Rae-1 (RMA-Rae1) to the same extent as C373AKI/KI mice, but hadno effect on the already enhanced NK cytotoxicity in Cbl-b-mutant mice. LDC1267 markedly reducedmetastatic spreading of melanomas; NK1.1 depletion abolished the therapeutic benefits of LDC1267.LDC1267 treatment significantly reduced the numbers and sizes of 4T1 micro-metastases in the liver,without any apparent effect on the primary vehicle LDC1267 mammary tumor. NK cell depletion usinganti-asialoGM1 antibodies resulted in markedly enhanced 4T1 liver metastases and abolished thetherapeutic benefits of LDC1267. Oral LDC1267 significantly reduced 4T1 liver micro-metastases. [1]References:
[1]. Paolino M, Choidas A2, Wallner S et al. The E3 ligase Cbl-b and TAM receptors regulate cancermetastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12. doi: 10.1038/nature12998.Epub 2014 Feb 19.
Caution: Producthasnot been fully validated for medical applications. For research use only.
Tel: (626) 353-8530 Fax: (626) 353-8530 E-mail: tech@glpbio.com
Address: 10292 Central Ave. #205, Montclair, CA, USA
3www.glpbio.com
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