(Z)-LFM-A13
Based on 3 publication(s) in Google Scholar
LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC50s of 2.5 μM, 10 μM and 61 μM; LFM-A13 shows no effects on JAK1 and JAK3, Src family kinase HCK, EGFR and IRK.
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- Purity: 99.80%
- CAS No.: 244240-24-2
- 화학식: C11H8Br2N2O2
- 분자량:360.01
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
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Publications Citing Use of MedChemExpress (MCE) (Z)-LFM-A13
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Customer Validation & Images
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WB
Biological Activity
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Plx1 10 μM (IC50) |
PLK3 61 μM (IC50) |
BRK 267 μM (IC50) |
BMX 281 μM (IC50) |
FYN 240 μM (IC50) |
Hepatocyte growth factor receptor kinase (Met) 215 μM (IC50) |
BTK 2.5 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| Platelet | IC50 |
2.8 μM
Compound: 36
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Inhibition of collagen-induced human platelet aggregation preincubated for 20 mins followed by collagen stimulation and measured for 10 mins by aggregometry
Inhibition of collagen-induced human platelet aggregation preincubated for 20 mins followed by collagen stimulation and measured for 10 mins by aggregometry
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[PMID: 32463237] |
| Sf21 | IC50 |
10.3 μM
Compound: LFM-A13
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Inhibition of xenopus recombinant Plx1 expressed in Sf21 cells by measuring autophosphorylation by 15-mins kinase assay
Inhibition of xenopus recombinant Plx1 expressed in Sf21 cells by measuring autophosphorylation by 15-mins kinase assay
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[PMID: 17098432] |
| Sf21 | IC50 |
32.5 μM
Compound: LFM-A13
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Inhibition of Xenopus recombinant Plx1 expressed in Sf21 cells by GST-Cdc25 substrate phosphorylation assay
Inhibition of Xenopus recombinant Plx1 expressed in Sf21 cells by GST-Cdc25 substrate phosphorylation assay
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[PMID: 17098432] |
LFM-A13 significantly inhibits BTK activity with an IC50 of 6.2 ± 0.3 μg/mL (= 17.2 ± 0.8 μM). The calculated Kis of LFM-A13 for BTK, JAK1, JAK3, IRK, EGFR and HCK are 1.4, 110, 148, 31.6, 166 and 214 μM. LFM-A13 (200 μM) markedly increases the chemosensitivity of ALL-1 cells to ceramide-induced apoptosis[1]. LFM-A13 (100 μM) suppresses Epo-induced phosphorylation of EpoR, Jak2, Btk, Stat5 and Erk1/2 in R10 cells. LFM-A13 (100 μM) inhibits auto-phosphorylation of Jak2, Tec and Btk rather than Lyn kinase auto-phosphorylation in COS cells[2]. LFM-A13 potently inhibits Plx1 with IC50 of 10 μM; also inhibits BRK, BMX, FYN and with IC50s of 267, 281, 240 and 215 μM[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 244240-24-2
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Appearance Solid
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분자량 360.01
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화학식 C11H8Br2N2O2
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Color Light yellow to yellow
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SMILES
BrC1=C(NC(/C(C#N)=C(C)\O)=O)C=C(Br)C=C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (3)
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Journal Impact Factor
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Most Recent
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Sci Immunol
SLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors. [Abstract]2022 Jan 21;7(67):eabj5501. PMID: 35061505 -
Dig Dis Sci
Effects of Tec Tyrosine Kinase Inhibition on the Inflammatory Response of Severe Acute Pancreatitis-Associated Acute Lung Injury in Mice. [Abstract]2019 Aug;64(8):2167-2176. PMID: 30761473 -
Oncotarget
BMX/Etk promotes cell proliferation and tumorigenicity of cervical cancer cells through PI3K/AKT/mTOR and STAT3 pathways. [Abstract]2017 Jul 25;8(30):49238-49252. PMID: 28514765
(Z)-LFM-A13 purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Jul 25;8(30):49238-49252. [Abstract]
HeLa and SiHa cells are treated with DMSO and LFM-A13, a pharmacologic inhibitor of BMX, and the phosphorylation and total BMX levels are determined using a western blot analysis.
용액&용해도
DMSO : ≥ 42 mg/mL (116.66 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.94 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (6.94 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Purified His6-Plx1 (250 ng) is added to a 20 μL reaction mixture containing 1× kinase buffer (10 mM Tris-HCl, pH 7.5, 10 mM MgCl2, and 1 mM TT), 25 μM cold ATP, and 1 μCi [γ-32P]ATP in the presence of different concentrations of LFM-A13 ranging from 5 μg/mL (13.9 μM) to 100 μg/mL (278 μM). The reaction mixtures are incubated at room temperature for 15-30 min and autophosphorylation is stopped by addition of 2× SDS-PAGE reducing sample buffer. A parallel experiment is performed in the presence of cold ATP. The kinase reactions are then subjected to immunoblotting using the commercially available anti-Plk antibodies. The immunoblots confirmed that the same amount of Plx1 protein is present in each reaction. In addition, we also examined the effects of LFM-A13 on substrate phosphorylation by Plx1. In brief, 250 ng of purified Plx1 is first incubated at room temperature for one hour with different concentrations of LFM-A13. After one hour of incubation, the tubes containing the reaction mixtures are put on ice and the substrate, GST-Cdc25 peptide (254-316) (200 ng), kinase buffer, and [γ-32P]ATP are added and the kinase reaction allowed to proceed for 15 min at room temperature. Immunoblotting with anti-Cdc25 antibodies is used to confirm that equal amounts of the substrate peptide are present in each reaction mixture. Anti-Plk antibodies, the polyclonal antibodies to gluthathione-S-transferase (GST) and ECL kit are used in the assay. The mode of human PLK3 inhibition by LFM-A13 is examined in titration experiments using increasing concentrations of [γ-32P]ATP and purified N-terminal His6-tagged recombinant human PLK3, residues 19-301, expressed by baculovirus in Sf21 insect cells. In brief, in a final reaction volume of 25 μL, PLK3 (h) (5-10 mU) is incubated with 8 mM MOPS, pH 7.0, 0.2 mM EDTA, 2 mg/mL casein, 10 mM Mg acetate, and [γ-32P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 min at room temperature, the reaction is stopped by the addition of 5 μL of a 3% phosphoric acid solution. Ten microliters of the reaction is then spotted onto a P30 filtermat and washed three times for 5 min in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting. The Ki of PLK3 by LFM-A13 is calculated from the reciprocal plots of the intensity of phosphorylation of the substrate (1/v) versus the concentration of the inhibitor (i) (viz., LFM-A13). From this Dixon plot, the Ki represents the dissociation constants of the EI complex, which is determined by the point of linear intersection[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[4]
Neu transgenic mice carrying one or more tumors are randomLy placed in the study. For the evaluation of tumor kinetics, tumor-bearing mice are randomLy assigned to either vehicle control or treatment groups. Tumor growth is determined by the measurement of tumors with a caliper in three dimensions three days a week and expressed as tumor volume in cubic millimeters (mm3). Tumor volumes are calculated using the formula for the volume of a prolate spheroid, V = 4/3 × 3. 14 × length/2 × width/2 × depth/2. Due to the large heterogeneity in transgenic tumor volumes on day 0, tumor growth for each mouse is normalized to the starting volume for that particular tumor. Therefore, each mouse also serves as its own control, and the tumor growth curves are generated to show the rate of change in tumor volumes. LFM-A13 (10 or 50 mg/kg) is administered by twice daily intraperitoneal injections on 5 consecutive days per week. Paclitaxel is administered intraperitoneally on days 1, 3, 5, 8, 10, and 12 at a dose level of 6.7 mg/kg. Gemcitabine is administered on days 1, 8, and 15 at a dose level of 33.7 mg/kg.
Rats[4]
Lewis rats are kept in microisolater cages containing autoclaved food, water, and bedding. Lewis rats are treated with i.v. injections of LFM-A13 at multiple dose levels. LFM-A13 is administered as a 0.5 mL bolus injection containing 10% DMSO as a vehicle. Animals are electively sacrificed on day 7 to determine the toxicity of LFM-A13 by evaluating multiple organs for the presence of toxic lesions. Blood is collected by intracardiac puncture following anesthesia with ketamine:xylazine and immediately heparinized. Blood counts (red blood cells [RBC], white blood cells [WBC], and platelets [Plt]) are determined using a HESKA Vet ABC-Diff Hematology Analyzer. Absolute neutrophil counts (ANC) and absolute lymphocyte counts (ALC) are calculated from WBC values after determining the percentages of neutrophils and lymphocytes by a manual differential count. Values for the laboratory parameters are pooled for vehicle controls and LFM-A13 treatments, and for each parameter differences between means are evaluated for statistical significance using Students t-test (vehicle vs LFM-A13 treatment, unequal variances, two-tailed). The calculations are performed in Excel spreadsheets. To determine significant effects, the p-values are adjusted using the Bonferroni method to control for random variation. For histopathologic studies, formalin fixed tissues are dehydrated and embedded in paraffin by routine methods. Glass slides with affixed 4-5 micron tissue sections are prepared and stained with hematoxylin and eosin.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
순도&문서
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Data Sheet (285 KB)
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SDS (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Mahajan S, et al. Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J Biol Chem. 1999 Apr 2;274(14):9587-99. [Content Brief]
[2]. van den Akker E, et al. The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity. Biol Chem. 2004 May;385(5):409-13. [Content Brief]
[3]. "Sahin K, et al. LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice. Invest New Drugs. 2017 Nov 15. " [Content Brief]
[4]. Uckun FM, et al. Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK). Bioorg Med Chem. 2007 Jan 15;15(2):800-14. Epub 2006 Oct 26. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7777 mL | 13.8885 mL | 27.7770 mL | 69.4425 mL |
| 5 mM | 0.5555 mL | 2.7777 mL | 5.5554 mL | 13.8885 mL | |
| 10 mM | 0.2778 mL | 1.3889 mL | 2.7777 mL | 6.9443 mL | |
| 15 mM | 0.1852 mL | 0.9259 mL | 1.8518 mL | 4.6295 mL | |
| 20 mM | 0.1389 mL | 0.6944 mL | 1.3889 mL | 3.4721 mL | |
| 25 mM | 0.1111 mL | 0.5555 mL | 1.1111 mL | 2.7777 mL | |
| 30 mM | 0.0926 mL | 0.4630 mL | 0.9259 mL | 2.3148 mL | |
| 40 mM | 0.0694 mL | 0.3472 mL | 0.6944 mL | 1.7361 mL | |
| 50 mM | 0.0556 mL | 0.2778 mL | 0.5555 mL | 1.3889 mL | |
| 60 mM | 0.0463 mL | 0.2315 mL | 0.4630 mL | 1.1574 mL | |
| 80 mM | 0.0347 mL | 0.1736 mL | 0.3472 mL | 0.8680 mL | |
| 100 mM | 0.0278 mL | 0.1389 mL | 0.2778 mL | 0.6944 mL |
(Z)-LFM-A13 Related Classifications
HY-18009 Related Classifications
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