CXJ2080
CXJ2080 is a selective PROTAC-based CDK7 degrader with a DC50 of 0.88 nM. CXJ2080 recruits VHL E3 ligase to induce ubiquitin-proteasome-dependent CDK7 degradation, disrupts the CDK7-cyclin H-MAT1 complex, suppresses CDK7-dependent phosphorylation of RNA polymerase II CTD Ser5, CDK1 Thr161, and CDK2 Thr160. CXJ2080 activates the p53-p21 axis, suppresses MYC-driven signaling, induces leukemia cell cycle arrest, apoptosis, and differentiation, reduces CD117 expression, spares platelets and normal PBMCs, maintains sustained CDK7 degradation post-washout. CXJ2080 can be used for the research of acute leukemia.
(Pink: CDK7 ligand (HY-183071); Blue: VHL ligand (HY-170348); Black: linker).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C51H68ClN11O6S2
- 分子量:1030.74
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保管条件:
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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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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生物活性
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CDK7 |
CXJ2080 (0.5-200 nM; 6 h) potently degrades CDK7 in MV4-11 acute myeloid leukemia cells with a DC50 of 0.88 nM and >98% maximum degradation efficiency[1].
CXJ2080 (72 h) potently inhibits the proliferation of RS4;11 acute lymphoblastic leukemia cells (IC50 = 17.29 nM) and MV4-11 acute myeloid leukemia cells (IC50 = 4.31 nM)[1].
CXJ2080 (72 h) inhibits the proliferation of primary acute myeloid leukemia patient-derived cell samples[1].
CXJ2080 (100 nM; 4 h pretreatment) induces sustained CDK7 degradation in MV4-11 acute myeloid leukemia cells, with suppression maintained for 48 h post-washout[1].
CXJ2080 (5-100 nM; 8 h) induces dose-dependent CDK7 degradation, p53 accumulation, Myc downregulation, and a biphasic p21 protein response in MV4-11 acute myeloid leukemia cells[1].
CXJ2080 (5-100 nM; 12 h) induces dose-dependent cell cycle arrest in MV4-11 acute myeloid leukemia cells, with increased SubG1 phase accumulation at higher concentrations[1].
CXJ2080 (5-100 nM; 48 h) induces dose-dependent apoptosis in MV4-11 acute myeloid leukemia cells[1].
CXJ2080 (5-100 nM; 24 h) significantly reduces CD117 (c-KIT) stemness marker expression in MV4-11 acute myeloid leukemia cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 acute myeloid leukemia cells
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Concentration:100 nM
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Incubation Time:4 h
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Result:Maintained CDK7 degradation for 48 h post-washout.
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Cell Line:MV4-11 acute myeloid leukemia cells
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Concentration:5 nM; 20 nM; 100 nM
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Incubation Time:8 h
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Result:Degraded CDK7 in a dose-dependent manner.
Induced accumulation of p53 protein.
Downregulated Myc protein.
Caused a biphasic response in p21 protein levels (upregulated at low concentrations, downregulated at high concentrations).
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Cell Line:MV4-11 acute myeloid leukemia cells
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Concentration:5 nM; 20 nM; 100 nM
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Incubation Time:12 h
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Result:Induced cell cycle arrest in a dose-dependent manner.
Increased accumulation of cells in the SubG1 phase at higher concentrations.
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Cell Line:MV4-11 acute myeloid leukemia cells
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Concentration:5 nM; 20 nM; 100 nM
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Incubation Time:48 h
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Result:Induced apoptosis in a dose-dependent manner.
Showed a higher proportion of apoptotic cells observed at higher concentrations.
Exhibited more potent apoptotic effects than TZ1104.
CXJ2080 (20-50 mg/kg; i.v.; every other day; 3 weeks) administered at 50 mg/kg every other day via intravenous injection achieves potent tumor growth inhibition with selective CDK7 degradation in MV4-11 xenograft tumors, while sparing PBMCs and maintaining normal platelet parameters[1].
CXJ2080 (20 mg/kg; i.v.; every other day; 21 days) administered at 20 mg/kg every other day via intravenous injection significantly improves survival in mice with disseminated Molm13 acute myeloid leukemia[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nu/Nu (female; 6-8 weeks old; implanted subcutaneously in
the right flank with 5 × 106 RS4;11 cells for a RS4;11 subcutaneous xenograft model)[1] -
Dosage:20 mg/kg; 50 mg/kg
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Administration:i.v.; every other day; 2 weeks
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Result:Resulted in tumor weights similar to vehicle controls at 20 mg/kg.
Significantly reduced tumor weights relative to vehicle controls at 50 mg/kg.
Achieved robust CDK7 degradation in tumor tissues at 50 mg/kg.
Caused no significant reduction in CDK7 levels in PBMCs at 50 mg/kg.
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Animal Model:Nu/Nu (female; 6-8 weeks old; implanted subcutaneously in
the right flank with 5 × 106 MV4-11cells for a MV4-11 subcutaneous xenograft model)[1] -
Dosage:20 mg/kg; 50 mg/kg
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Administration:i.v.; every other day; 3 weeks
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Result:Resulted in tumor weights similar to vehicle controls at 20 mg/kg.
Significantly reduced tumor weights relative to vehicle controls at 50 mg/kg.
Achieved robust CDK7 degradation in tumor tissues at 50 mg/kg.
Caused no significant reduction in CDK7 levels in PBMCs at 50 mg/kg.
Maintained stable platelet counts, platelet-large cell ratio (P-LCR), and plateletcrit (PCT) throughout the treatment period at 50 mg/kg.
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Animal Model:NOD scid gamma (NSG) (female; 6-8 weeks old; inoculated intravenously with 2 × 104
Molm13 cells via the tail vein for a Molm13 disseminated xenograft model)[1] -
Dosage:20 mg/kg
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Administration:i.v.; every other day; 21 days
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Result:Significantly extended the survival of Molm13 tumor-bearing mice relative to vehicle controls.
Maintained a low leukemia burden in spleens of two surviving mice at the experimental endpoint.
化学情報
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分子量 1030.74
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分子式 C51H68ClN11O6S2
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SMILES
O=C([C@H]1N(C([C@@H](N2N=NC(CCCCCCC(N[C@H]3CC[C@H](NC4=NC=C(Cl)C(NC5=CC=CC=C5S(=O)(C(C)C)=O)=N4)CC3)=O)=C2)C(C)(C)C)=O)C[C@H](O)C1)N[C@H](C6=CC=C(C7=C(C)N=CS7)C=C6)C
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
CXJ2080 関連分類
HY-183070 関連分類
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