NCD38
NCD38 is a Lysine-specific demethylase 1 (LSD1) inhibitor with a target IC50 of 0.59 μM. NCD38 selectively disrupts LSD1-GFI1B interactions, dissociates LSD1 and CoREST from the ERG super-enhancer. NCD38 increases apoptosis-related protein levels, induces apoptosis and reduces SOX2 and Oct4 levels. NCD38 can be used for the research of acute myeloid leukemia.
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- No. CAS: 1456907-39-3
- Fòrmula: C35H36ClN3O2
- Peso molecular:566.13
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Actividad biológica
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LSD1 |
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Cell Line
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Type | Value | Description | References |
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| HeLa | GI50 |
4.3 μM
Compound: NCD38
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Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay
Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay
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[PMID: 32931269] |
NCD38 (2 μM; 24 h) selectively disrupts the interaction between GFI1B and the LSD1-CoREST-HDAC1/2 complex in HEL cells[1].
NCD38 (2 μM; 24 h) induces significant upregulation of ERG transcripts in HEL cells[1].
NCD38 (2 μM; 48 h) induces ERG protein expression and downregulates the erythroid marker CD235a in HEL cells[1].
NCD38 (2 μM; 24 h) reduces LSD1 and CoREST occupancy at the ERG super-enhancer in HEL cells[1].
NCD38 potently and selectively inhibits purified LSD1 protein with an IC50 of 0.59 μM, with no activity against MAO A or MAO B[2].
NCD38 (0.5-2 μM; 6-9 days) dose-dependently inhibits the proliferation of HEL, CMK11-5, and MDS-L leukemia cells[2].
NCD38 (2 μM; 48-72 h) induces myeloid differentiation in HEL, CMK11-5, and MDS-L leukemia cells by increasing CD11b expression, decreasing erythroid marker expression, and driving morphologic maturation[2].
NCD38 (2 μM; 2-6 days) induces G0/G1 cell cycle arrest in HEL, CMK11-5, and MDS-L leukemia cells[2].
NCD38 (2 μM; 48 h) activates myeloid development programs and attenuates oncogenic leukemia stem cell programs in HEL, MDS-L, and CMK11-5 leukemia cells, upregulating 89 common genes including key hematopoietic regulators[2].
NCD38 (2 μM; 3-48 h) activates the GFI1 super-enhancer within 3 h of treatment in HEL leukemia cells, preceding increases in GFI1 transcript levels (after 12 h) and myeloid differentiation marker CD11b expression (after 24 h)[2].
NCD38 (2 μM; 48 h)-induced myeloid differentiation in HEL leukemia cells is significantly attenuated in GFI1-knockout sublines[2].
NCD38 (2-5 μM; 10-14 days) inhibits colony formation and induces myeloid differentiation in primary human AML and MDS leukemia cells, while sparing healthy donor hematopoietic cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human erythroleukemia HEL cells
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Concentration:2 μM
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Incubation Time:24 h
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Result:Increased ERG transcript levels with statistical significance (P < 0.01) relative to DMSO-treated controls.
Made ERG transcripts detectable, as they were barely detectable in untreated HEL cells.
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Cell Line:HEL erythroid leukemia cells, CMK11-5 megakaryoblastic leukemia cells, MDS-L MDS-derived leukemia cells
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Concentration:0.5 μM; 1 μM; 2 μM
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Incubation Time:6 days; 9 days
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Result:Dose-dependently reduced cell viability in all three cell lines compared to DMSO control.
Caused a significant decrease in HEL cell number (p<0.01) at 2 μM after 6 days.
Caused a significant decrease in CMK11-5 cell number (p<0.01) at 2 μM after 6 days.
Caused a significant decrease in MDS-L cell number (p<0.01) at 2 μM after 9 days.
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Cell Line:HEL erythroid leukemia cells, CMK11-5 megakaryoblastic leukemia cells, MDS-L MDS-derived leukemia cells
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Concentration:2 μM
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Incubation Time:48 h; 72 h
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Result:Increased the mean fluorescence intensity (MFI) of CD11b from 6.6 to 13.2 in HEL, from 47.2 to 93.3 in CMK11-5, and from 31.9 to 56.9 in MDS-L.
Decreased the MFI of CD71 from 121 to 49 and CD235a from 640 to 382 in HEL.
Decreased the MFI of CD71 from 116 to 81.9 and CD235a from 270 to 161 in CMK11-5.
Induced morphologic maturation to mature myeloid cells in MDS-L cells.
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Cell Line:HEL erythroid leukemia cells, CMK11-5 megakaryoblastic leukemia cells, MDS-L MDS-derived leukemia cells
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Concentration:2 μM
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Incubation Time:2 days; 6 days
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Result:Increased the percentage of cells in the G0/G1 phase in all three cell lines compared to DMSO control.
Decreased the percentage of cells in the S phase in all three cell lines compared to DMSO control.
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Cell Line:GFI1-knockout HEL erythroid leukemia cells
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Concentration:2 μM
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Incubation Time:48 h
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Result:Did not induce GFI1 protein in GFI1-knockout sublines, unlike control sublines.
Significantly attenuated the induction of CD11b mean fluorescence intensity (MFI) in GFI1-knockout sublines compared to control sublines (p<0.005).
NCD38 (repeated 1-week on/off) improves survival in NSG mice bearing MDS-related leukemia with complex karyotype, with 75% of treated mice surviving beyond 4 months[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.Cg-Prkdc/SzJ (NSG) (6-week-old, sublethally irradiated 150 cGy, MDS-related leukemia engrafted)[2]
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Dosage:20 mg/kg
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Administration:i.p.; daily; 10 days
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Result:Achieved long-term survival of at least 28 weeks post-transplantation.
Maintained human CD45-positive cell proportions at 0.0% to 5.2% at 12 weeks post-transplantation.
Maintained human CD45-positive cell proportions at 0.0% to 0.1% at 28 weeks post-transplantation.
Chemical Information
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No. CAS 1456907-39-3
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Peso molecular 566.13
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Fòrmula C35H36ClN3O2
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SMILES
O=C(C1=CC=C(C2=CC=CC=C2)C=C1)N[C@H](C(NCC3=CC(Cl)=CC=C3)=O)CCCCNC4C(C5=CC=CC=C5)C4
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Yamamoto R, et al. Selective dissociation between LSD1 and GFI1B by a LSD1 inhibitor NCD38 induces the activation of ERG super-enhancer in erythroleukemia cells. Oncotarget. 2018;9(30):21007-21021. Published 2018 Apr 20. [Content Brief]
[2]. Sugino N, et al. A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers. Leukemia. 2017 Nov;31(11):2303-2314. [Content Brief]
[3]. Dai XJ, et al. Tranylcypromine Based Lysine-Specific Demethylase 1 Inhibitor: Summary and Perspective. J Med Chem. 2020;63(23):14197-14215. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
NCD38 Related Classifications
HY-183202 Related Classifications
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