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| 25mg |
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Purity: ≥98%
LDC1267 (LDC-1267) is a novel, highly potent and selective TAM (Tyro3, Axl and Mer) kinase inhibitor with potential antitumor activity. It has lower effects on other kinases like Met, Aurora B, Lck, Src, and CDK8, and inhibits Mer, Tyro3, and Axl with IC50s of<5 nM, 8 nM, and 29 nM, respectively. In the mouse B16F10 metastatic melanoma model, it exhibits outstanding in vivo antitumor efficacy.
| Targets |
Mer (IC50 <5 nM); Tyro3 (IC50 = 8 nM); Axl (IC50 = 29 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
Kinase tracer 236 and the HTRF method have established an Axl binding assay for the purpose of optimizing Axl/TAM receptor inhibitors. The basis of this assay is the binding and displacement of each glutathione S-transferase (GST)-tagged kinase utilized in the binding assay by the Alexa Fluor 647-labelled Kinase tracer 236, as demonstrated by this method. Utilizing anti-GST antibodies labeled with europium (Eu), the tracer's binding to the kinase was distinguished. A fluorescence resonance energy transfer (FRET) signal is produced when the fluorescent tracer and the Eu-labeled antibodies bind to the GST-tagged kinase simultaneously. The FRET signal is lost when the inhibitor binds to the kinase and competes with the tracer for binding. The chemical is diluted in 20 mM HEPES, pH 8.0, 1 mM DTT, 10 mM MgCl2, and 0.01% Brij35 for the assay. Next, the compound dilutions ranging from 5 nM to 10 μM are combined with the kinase of interest (5 nM final concentration), fluorescent tracer (15 nM final concentration), and LanthaScreen Eu-anti-GST antibody (2 nM final concentration) and incubated for a duration of 1 hour. An EnVision Multilabellreader 2104 is used to quantify the FRET signal.
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| Cell Assay |
CellTiterGlow reagent is used to measure the proliferation in comparison to the corresponding DMSO control after the LDC1267 is incubated for 72 hours.
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| Animal Protocol |
Mouse B16F10 metastatic melanoma model
20 mg/kg i.p. |
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| References |
| Molecular Formula |
C30H26F2N4O5
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| Molecular Weight |
560.55
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| Exact Mass |
560.187
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| Elemental Analysis |
C, 64.28; H, 4.68; F, 6.78; N, 10.00; O, 14.27
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| CAS # |
1361030-48-9
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| Related CAS # |
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| PubChem CID |
56847486
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
628.4±55.0 °C at 760 mmHg
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| Flash Point |
333.8±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.610
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| LogP |
6.48
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
41
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| Complexity |
860
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C([H])=C([H])C(=C(C([H])([H])[H])C=1[H])N1C([H])=C(C(C(N([H])C2C([H])=C([H])C(=C(C=2[H])F)OC2C([H])=C([H])N=C3C([H])=C(C(=C([H])C3=2)OC([H])([H])[H])OC([H])([H])[H])=O)=N1)OC([H])([H])C([H])([H])[H]
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| InChi Key |
ISPBCAXOSOLFME-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-4-ethoxy-1-(4-fluoro-2-methylphenyl)pyrazole-3-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.46 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10 mg/mL (17.84 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7840 mL | 8.9198 mL | 17.8396 mL | |
| 5 mM | 0.3568 mL | 1.7840 mL | 3.5679 mL | |
| 10 mM | 0.1784 mL | 0.8920 mL | 1.7840 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
a, TC-1 tumour growth in Cbl-b+/+ Rag2−/− and Cbl-b−/− Rag2−/− mice (mean ± s.e.m., n = 10 each). ***P |
a, In vitro Cbl-b-dependent ubiquitylation of Tyro3, Axl and Mer (anti-Ub). Control, no TAM receptors. Loading controls are shown. b, IFN-γ+ Cbl-b+/− and Cbl-b−/− NK cells (%) stimulated with anti-NKG2D antibodies in the presence of sol…Nature. 2014 Mar 27;507(7493):508-12. |
a, Kinetics of primary 4T1 tumour cell growth in the mammary fat pad of control and anti-asialo GM1-treated mice that received LDC1267 or vehicle (mean ± s.e.m., n = 6–9 mice per group). NS, not significant (one-way ANOVA). Nature. 2014 Mar 27;507(7493):508-12. |
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