EP652
EP652 is a METTL3 inhibitor and antitumor agent with IC50 values of 2 nM, <10 nM, and 37 nM in SPA, intracellular, and ATPlite assays, respectively. EP652 exhibits high selectivity against 40 other methyltransferases and FTO, and possesses favorable pharmacokinetic parameters. EP652 reduces intracellular N6-methyladenosine (m6A) levels in mRNA. EP652 inhibits tumor growth and progression of both hematologic malignancies and solid tumors. EP652 can be used for the research of acute myeloid leukemia, ovarian cancer, non-small cell lung cancer, and hypopharyngeal squamous cell carcinoma.
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- CAS No.: 3050819-22-9
- 화학식: C25H34N8O
- 분자량:462.59
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
In Vitro
EP652 (range; 24 h for Calu-6) potently reduces intracellular m6A levels across multiple liquid and solid tumor cell lines, with IC50 values ranging from 3 nM to 9 nM, including an IC50 of 8.6 nM in Calu-6 cells after 24-hour treatment[1].
EP652 inhibits 3D spheroid proliferation of NCI-H1650 lung cancer cells with an IC50 of 99 nM[1].
EP652 (respective IC50 concentrations; 72 h) modulates key oncogenic and pro-apoptotic biomarkers in solid tumor cell lines after 72-hour treatment at their respective IC50 concentrations, reducing Bcl-2 levels and increasing Bax levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Kasumi-1, MV-4-11, Caov-3, Calu-6, A549, FaDu, SK-OV-3
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Concentration:Range (to determine IC50 values)
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Incubation Time:72 h
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Result:Demonstrated dose-dependent antiproliferative activity with IC50 values of 37 nM (Kasumi-1), 234 nM (MV-4-11), 20 nM (Caov-3), 18 nM (Calu-6), 169 nM (A549), 50 nM (FaDu), and 11 nM (SK-OV-3).
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Cell Line:SK-OV-3, FaDu, A549
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Concentration:IC50 concentration (respective cell lines)
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Incubation Time:72 h
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Result:Downregulated the oncogenic biomarker Bcl-2 (relative expression: 0.9 in SK-OV-3, 0.6 in FaDu, 0.3 in A549) compared to DMSO-treated controls.
Upregulated the pro-apoptotic biomarker Bax (relative expression: 1.6 in SK-OV-3, 1.9 in FaDu, 1.6 in A549) compared to DMSO-treated controls.
Parmacokinetics
In Vivo
EP652 (30 mg/kg; intraperitoneal injection; once daily; for 91 consecutive days) significantly prolongs the survival of patient-derived xenograft models of acute myeloid leukemia, with a 100% survival rate on day 112[1].
EP652 (10-30 mg/kg; i.p.; once daily; days 19 to 31) inhibits the progression of acute myeloid leukemia, reduces the human cancer cell burden in the blood, bone marrow and spleen, and a dose-dependent response is observed at the doses of 10 mg/kg and 30 mg/kg[1].
EP652 (30 mg/kg; i.p.; once daily) prolongs the survival time of mice in orthotopic xenograft models of non-small cell lung cancer and subcutaneous xenograft models of pharyngeal squamous cell carcinoma, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley rats (male)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:i.p.; daily; 2 days
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Result:Induced a maximum ~75% reduction in cellular m6A levels in peripheral blood mononuclear cells at the 0.3 mg/kg dose.
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Animal Model:NSG mice with Acute myeloid leukemia (female; orthotopic patient-derived xenograft model via intratibial implantation of LEXFAM 4128 cells)[1]
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Dosage:30 mg/kg
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Administration:i.p.; daily; 91 days
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Result:Resulted in 100% survival of mice up to study conclusion on day 112, compared to vehicle control mice which had 0% survival by day 60.
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Animal Model:NSG mice with Acute myeloid leukemia (female; disseminated cell line-derived xenograft model via intravenous implantation of 2×106 MV-4-11-Luc-mCh-Puro cells)[1]
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Dosage:10 mg/kg (day 19 bioluminescence assessment); 30 mg/kg (31-day treatment)
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Administration:i.p.; daily; 19 days (10 mg/kg); daily; 31 days (30 mg/kg)
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Result:Inhibited AML progression as measured by bioluminescence imaging at 30 mg/kg.
Showed selective decreases in hCD45+ human cancer cells in bone marrow, blood, and spleen (reaching near-undetectable levels in bone marrow and spleen) at 30 mg/kg.
Induced a dose-dependent reduction in bioluminescence signal on day 19 post-implant at 10 mg/kg and 30 mg/kg.
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Animal Model:NSG mcie with Ovarian cancer (female; orthotopic cell line-derived xenograft model via implantation of SK-OV-3 cells)[1]
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Dosage:30 mg/kg
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Administration:i.p.; daily
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Result:Inhibited tumor growth as measured by bioluminescence imaging, with sustained low signal levels compared to vehicle control.
Significantly improved survival (p < 0.01) relative to vehicle control.
Caused minimal body weight loss and no macroscopic adverse events.
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Animal Model:Subcutaneous cell line-derived xenograft mice model via implantation of FaDu cells[1]
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Dosage:30 mg/kg
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Administration:i.p.; daily
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Result:Significantly prolonged survival.
Inhibited tumor growth as measured by direct tumor volume assessment.
Caused minimal body weight loss and no macroscopic adverse events.
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Animal Model:Orthotopic cell line-derived xenograft mice model via implantation of A549 cells[1]
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Dosage:30 mg/kg
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Administration:i.p.; daily
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Result:Significantly prolonged survival relative to vehicle control.
Caused minimal body weight loss and no macroscopic adverse events.
Chemical Information
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CAS No. 3050819-22-9
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분자량 462.59
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화학식 C25H34N8O
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SMILES
C[C@H](N1C=CC(N2CCC[C@H](C2)NCC3CC3)=CC1=O)N4C=C(N=N4)C5=CC(N(C)C)=CN=C5
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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)
EP652 Related Classifications
HY-168878 Related Classifications
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