TAS1440 benzoate
TAS1440 benzoate is an orally active LSD1/KDM1A inhibitor with a human IC50 of 4.8 nM. TAS1440 benzoate non-covalently binds to the histone H3-binding pocket of LSD1, inhibiting demethylase activity and disrupting repressive complexes with INSM1 and SMAD2. TAS1440 benzoate activates tumor-suppressive TGF-β and NOTCH signaling pathways via transcriptional reprogramming. TAS1440 benzoate can be used for the research of small cell lung cancer, specifically the SCLC-A subtype.
For research use only. We do not sell to patients.
- CAS No.: 2642224-15-3
- Formula: C35H33F2N3O4
- Molecular Weight:597.65
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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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KDM1/LSD1 4.8 nM (IC50) |
TAS1440 benzoate is a highly selective, histone H3-competitive inhibitor of purified recombinant human LSD1, with an IC50 of 4.8 nM and no significant activity against LSD2, MAO-A, MAO-B, or a broad panel of other epigenetic enzymes[1].
TAS1440 (0-7500 nM; 8 days) benzoate selectively inhibits proliferation of SCLC-A cell lines, with the greatest potency in NCI-H1417, NCI-H510A, NCI-H146, and COR-L51 cells, and exhibits stronger antiproliferative activity than covalent LSD1 inhibitors in these sensitive models[1].
TAS1440 (300 nM; 1-7 days) benzoate induces transcriptional reprogramming in SCLC cell lines, activating tumor-suppressive TGF-β and NOTCH pathways and suppressing neuroendocrine gene expression, with the most pronounced changes in TAS1440-sensitive SCLC-A cell lines[1].
TAS1440 (300 nM; 30 min-5 days) benzoate activates TGF-β and NOTCH signaling in SCLC-A cell lines by inducing SMAD2 phosphorylation, NOTCH1 upregulation, and nuclear accumulation of active pathway components, while also disrupting INSM1-LSD1 and SMAD2-LSD1 protein complexes more effectively than covalent LSD1 inhibitors[1].
TAS1440 (300 nM; 5 days) benzoate induces global epigenetic reprogramming in SCLC-A cell lines, increasing active histone marks (H3K4me1, H3K4me2, H3K27ac) at TSSs and promoting INSM1 and SMAD2 binding to tumor-suppressive NOTCH and TGF-β pathway gene promoters[1].
TAS1440 (100-3,000 nM; 7 days) benzoate antiproliferative and transcriptional effects in SCLC-A cell lines depend on LSD1 expression and catalytic activity, while its ability to disrupt INSM1/SMAD2-LSD1 complexes is independent of LSD1 catalytic function[1].
TAS1440 (300 nM; 2 h-10 days) benzoate requires INSM1 for its antiproliferative effects, transcriptional reprogramming, and activation of TGF-β/NOTCH signaling in SCLC-A cell lines[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:19 small cell lung cancer (SCLC) cell lines stratified into SCLC-A, SCLC-N, and SCLC-P subtypes
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Concentration:7500 nM
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Incubation Time:8 days
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Result:Showed the strongest growth suppression in SCLC-A cell lines compared to SCLC-N and SCLC-P subtypes.
Exhibited the lowest IC50 values in NCI-H1417, NCI-H510A, NCI-H146, and COR-L51 SCLC-A cells.
Exhibited greater potency than covalent LSD1 inhibitors in sensitive SCLC-A lines, as covalent comparators often had IC50 values ≥1,000 nM or were right-censored at the 7,500 nM testing limit.
Showed broadly similar inhibition patterns to another H3-competitive inhibitor (CC-90011) but greater potency in the most sensitive SCLC-A lines.
TAS1440 (50 mg/kg/day; p.o.; daily; 3 weeks) benzoate significantly reduces tumor growth in INSM1-wild-type but not INSM1-knockout NCI-H146 SCLC-A xenografts, demonstrating INSM1 dependence for in vivo efficacy[1].
TAS1440 (50 mg/kg/day; p.o.; daily; 4 weeks) benzoate reduces pulmonary tumor burden by 67% in an orthotopic NCI-H146 SCLC-A xenograft model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C.B-17 SCID mice (male, 6-week-old, subcutaneously injected with NCI‑H1417, NCI‑H146, NCI‑H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1]
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Dosage:16.7 mg/kg; 50 mg/kg
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Administration:p.o.; daily; 3 weeks
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Result:Significantly reduced tumor growth in NCI-H1417 xenografts compared with vehicle at 16.7 and 50 mg/kg/day.
Significantly reduced tumor growth in NCI-H146, NCI-H510A, and COR-L51 xenografts compared with vehicle at 50 mg/kg/day.
Upregulated NOTCH1 and increased phosphorylated SMAD2 (pSMAD2) in xenograft tumors.
Induced NOTCH/TGF-β pathway genes (NOTCH1, HES1, TGFB2, TGFBR2, ID3) and reduced ASCL1 and DLL3 in xenograft tumors.
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Animal Model:C.B-17 SCID mice (male, 6-week-old, subcutaneously injected with NCI‑H1417, NCI‑H146, NCI‑H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 3 weeks
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Result:Significantly reduced tumor growth in INSM1-wild-type NCI-H146 xenografts compared with vehicle.
Had no significant effect on tumor growth in INSM1-knockout NCI-H146 xenografts.
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Animal Model:C.B-17 SCID mice (male, 6-week-old, subcutaneously injected with NCI‑H1417, NCI‑H146, NCI‑H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 4 weeks
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Result:Reduced pulmonary tumor area by 67% compared with vehicle, as measured by micro-CT volumetric quantification.
Chemical Information
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CAS No. 2642224-15-3
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Molecular Weight 597.65
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Formula C35H33F2N3O4
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SMILES
O=C(O)C1=CC=CC=C1.N[C@H](C2)CCN2C(C(C=C3C4=CC=C(C#N)C(F)=C4)=CC=C3C5=CC=C(C=C5F)CC(C)(C)O)=O
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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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