SKLB06489
SKLB06489 is a selective and orally active inhibitor of type I PRMT enzymes, with IC50 values of 64.55 nM (PRMT1), 4.21 nM (PRMT6), and 51.27 nM (PRMT8). SKLB06489 inhibits cell proliferation, colony formation, DNA replication, and DNA damage repair in cancer cells. SKLB06489 induces G0/G1-phase cell cycle arrest and apoptosis in cancer cells. SKLB06489 enhances intracellular cholesterol efflux via ABCA1 and ABCG1 upregulation, disrupts cholesterol metabolic homeostasis, and suppresses tumor growth in subcutaneous xenograft models. SKLB06489 can be used for the research of triple-negative breast cancer (TNBC).
For research use only. We do not sell to patients.
- Formula: C25H33N5O
- Molecular Weight:419.56
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Storage:
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
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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PRMT1 64.55 nM (IC50) |
PRMT6 4.21 nM (IC50) |
PRMT8 51.27 nM (IC50) |
SKLB06489 (40 μM; 8 h) selectively and stably binds to PRMT1 and PRMT6 in HEK293T cells, enhancing their thermal stability[1].
SKLB06489 (5-7 days) dose-dependently inhibits proliferation of MDA-MB-231, Hs578T, and BT549 TNBC cells with IC50 values in the low micromolar range[1].
SKLB06489 (2.5-20 μM; 12-14 days) dose-dependently inhibits colony formation in MDA-MB-231, Hs578T, and BT549 TNBC cells[1].
SKLB06489 (2.5-10 μM; 6 days) dose-dependently reduces ADMA levels in MDA-MB-231 and Hs578T TNBC cells, indicating inhibition of type I PRMT enzymatic activity in cells[1].
SKLB06489 (5-20 μM; 1-3 days) dose- and time-dependently inhibits DNA replication in MDA-MB-231, Hs578T, and BT549 TNBC cells[1].
SKLB06489 (10 μM; 24 h) impairs DNA damage repair in MDA-MB-231 and Hs578T TNBC cells, with a more pronounced effect than MS023 in Hs578T cells[1].
SKLB06489 (5-20 μM; 24 h) dose-dependently induces G0/G1 phase cell cycle arrest in MDA-MB-231, Hs578T, and BT549 TNBC cells[1].
SKLB06489 (5-20 μM; 72 h) dose-dependently induces apoptosis in MDA-MB-231, Hs578T, and BT549 TNBC cells[1].
SKLB06489 (10 μM; 4 days) upregulates ABCA1 and ABCG1 mRNA expression in MDA-MB-231 and Hs578T TNBC cells[1].
SKLB06489 (5-10 μM; 4 days) dose-dependently enhances cholesterol efflux (increasing medium cholesterol) and reduces intracellular cholesterol in MDA-MB-231 and Hs578T TNBC cells[1].
SKLB06489 (5-10 μM) upregulates ABCG1 protein levels in MDA-MB-231 and Hs578T TNBC cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 and Hs578T cells
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Concentration:2.5 μM, 5 μM, 10 μM
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Incubation Time:6 days
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Result:Dose-dependently reduced ADMA levels without affecting PRMT1 or PRMT6 expression.
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Cell Line:MDA-MB-231, Hs578T, and BT549 cells
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Concentration:5 μM, 10 μM, 20 μM
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Incubation Time:24 h
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Result:Dose-dependently increased the proportion of cells in G0/G1 phase and decreased the proportion in S phase.
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Cell Line:MDA-MB-231, Hs578T, and BT549 cells
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Concentration:5 μM, 10 μM, 20 μM
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Incubation Time:72 h
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Result:Dose-dependently increased the percentage of apoptotic cells (early + late) in MDA-MB-231 (5.9% to 41.8% and 82.9%), Hs578T (20.7% to 68.4% and 79.9%), and BT549 (6.5% to 49.1% and 92.3%) cells at 10 and 20 μM, respectively.
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Cell Line:MDA-MB-231 and Hs578T cells
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Concentration:10 μM
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Incubation Time:4 days
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Result:Significantly upregulated ABCA1 (15.93-fold in MDA-MB-231, 13.90-fold in Hs578T) and ABCG1 (4.64-fold in MDA-MB-231, 3.79-fold in Hs578T) mRNA expression.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, aged 4-5 weeks, 6-week-old) bearing DA-MB-231 cells[1]
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Dosage:40 mg/kg; 80 mg/kg
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Administration:i.g.; daily; 33 days
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Result:Dose-dependently suppressed tumor growth; had a tumor growth inhibition (TGI) value of 58.4% at 80 mg/kg; reduced tumor weight compared to vehicle control; increased cleaved caspase-3-positive cells; decreased Ki67-positive cells in tumor tissues.
Chemical Information
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Molecular Weight 419.56
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Formula C25H33N5O
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SMILES
CNCCN(CC1=NNC2=CC=C(C=C21)C3=CC=C(C=C3)NC(C4CCCCC4)=O)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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