LAF389
LAF389, a prodrug of LAF153 (HY-183876), is a methionine aminopeptidase (MetAps) inhibitor with an IC50 of 800 nM against MetAp2, and exhibits a maximum inhibition rate of 20% against MetAp1 at 300 nM. LAF389 possesses antiproliferative, antiangiogenic and cytotoxic activities. LAF389 can be used in research related to cancers such as advanced solid tumors.
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- CAS No.: 270902-51-7
- 화학식: C25H42N2O8
- 분자량:498.61
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
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MetAp2 800 nM (IC50) |
MetAp1 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
13 nM
Compound: LAF389
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Antiproliferative activity against human A549 cells after 96 hrs
Antiproliferative activity against human A549 cells after 96 hrs
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[PMID: 28185457] |
| HCT-116 | IC50 |
23 nM
Compound: LAF389
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Antiproliferative activity against human HCT116 cells after 96 hrs
Antiproliferative activity against human HCT116 cells after 96 hrs
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[PMID: 28185457] |
| MDA-MB-435 | IC50 |
40 nM
Compound: LAF389
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Cytotoxicity against human MDA-MB-435 cells assessed as reduction in cell viability after 72 hrs by MTS assay
Cytotoxicity against human MDA-MB-435 cells assessed as reduction in cell viability after 72 hrs by MTS assay
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[PMID: 28185457] |
LAF389 potently inhibits monolayer proliferation of human cancer cell lines, including those unresponsive to standard cytotoxics or with drug resistance, and is more unaffected by P-glycoprotein overexpression than paclitaxel[1].
LAF389 (0.0001-10 μM; 72 h) inhibits proliferation of HUVEC (IC50 = 20 nM) and A549 human non-small cell lung carcinoma cells, with greater potency against endothelial cells and cytotoxic activity against A549 cells at micromolar concentrations[2].
LAF389 (3-300 nM; 8-48 h) induces a pH-shifted, unprocessed form of 14-3-3γ in H1299, U2OS, MDA-MB-435, and A549 cells, with detection starting at 3 nM after 24 h and accumulation over 48 h[2].
LAF389 (0.1-1000 nM; 18 h) inhibits processing of 14-3-3γ in HUVEC, inducing the unprocessed form with maximal response at 1 μM after 18 h of incubation[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A549 human non-small cell lung carcinoma cells, human umbilical vein endothelial cells (HUVEC)
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Concentration:0.0001, 0.001, 0.01, 0.1, 1, 10 μM
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Incubation Time:72 h
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Result:Potently inhibited HUVEC proliferation with an IC50 of 20 nM.
Inhibited A549 cell proliferation with roughly 10-fold lower potency.
Caused substantial cell death of A549 cells at micromolar concentrations.
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Cell Line:H1299 human small cell lung carcinoma cells, U2OS, MDA-MB-435, A549 human non-small cell lung carcinoma cells
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Concentration:3-300 nM (24 h incubation); 200 nM (8 h, 24 h, 48 h incubation)
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Incubation Time:8 h, 24 h, 48 h
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Result:Shifted the isoelectric point of the 14-3-3γ isoform to a more basic pH in H1299 cells.
Caused the shifted band to be detectable after 8 h of incubation and accumulate up to 48 h.
Induced effects starting at 3 nM LAF389 at 24 h, increasing up to 300 nM.
Confirmed the shifted band as the unprocessed form of 14-3-3γ, retaining its N-terminal methionine.
Induced the same effect in U2OS, MDA-MB-435, and A549 cells.
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Cell Line:human umbilical vein endothelial cells (HUVEC)
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Concentration:0.1, 0.3, 1, 3, 10 and 30 nM (18 h incubation); 1, 10, 100 and 1000 nM (18 h incubation)
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Incubation Time:18 h
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Result:Inhibited MetAp processing of 14-3-3γ, leading to detection of the unprocessed form via both isoform-specific polyclonal antibodies and the unprocessed-form-specific monoclonal antibody.
Caused maximal detection of the unprocessed form at 1 μM LAF389.
LAF389 (intravenous injection; repeated bolus administration; repeated cycle 3 times with a 7-day interval after 3 consecutive days of administration) exhibits significant, frequency-dependent tumor growth inhibition in a panel of human solid tumor xenograft models in immunocompromised mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 270902-51-7
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분자량 498.61
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화학식 C25H42N2O8
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SMILES
CC(C)(C)/C=C/[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC)C(N[C@H]1CC[C@H](CNC1=O)OC(C2CCCCC2)=O)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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