Ibulocydine
Ibulocydine is an isobutyrate prodrug of the Cdk inhibitor BMK-Y101 (HY-188159), with oral activity, and exhibits IC50 values of approximately 50 nM against CDK1/CDK2, 530 nM against CDK7/cyclin H/Mat1, and 85 nM against CDK9/cyclin T. Ibulocydine reduces the phosphorylation levels of Rb, nucleolin, and RNA polymerase II CTD Ser-5 and Ser-2, downregulates the expression of Mcl-1, survivin, and XIAP, decreases MMP-9 expression, and lowers the Bcl-2/Bax ratio, activates calpain-mediated Bax cleavage, cytochrome c release, and caspase activation. Ibulocydine induces apoptosis, inhibits the growth of cancer cells and xenografts, enhances the sensitivity of cancer cells to TRAIL and radiotherapy, and blocks cancer cell metastasis. Ibulocydine can be used in research related to various cancers, including hepatocellular carcinoma, triple-negative breast cancer, lung cancer, and colon cancer.
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- CAS 番号: 1314096-68-8
- 分子式: C16H20BrN5O6
- 分子量:458.26
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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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Help & FAQs
生物活性
製品説明
IC50 & Target
[1]|
CDK1 ~50 nM (IC50) |
CDK2 ~50 nM (IC50) |
CDK7/Cyclin H/MAT1 530 nM (IC50) |
CDK9/cyclinT1 85 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| SNU-354 | IC50 |
0.45 μM
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Inhibition of Cdk7-mediated Ser-5 phosphorylation of RNA polymerase II in human HCC SNU-354 cells assessed via Western blot analysis after 24 h incubation.
Inhibition of Cdk7-mediated Ser-5 phosphorylation of RNA polymerase II in human HCC SNU-354 cells assessed via Western blot analysis after 24 h incubation.
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21478145 |
| SNU-354 | IC50 |
0.33 μM
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Inhibition of Cdk9-mediated Ser-2 phosphorylation of RNA polymerase II in human HCC SNU-354 cells assessed via Western blot analysis after 24 h incubation.
Inhibition of Cdk9-mediated Ser-2 phosphorylation of RNA polymerase II in human HCC SNU-354 cells assessed via Western blot analysis after 24 h incubation.
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21478145 |
| Hs-578T | IC50 |
3.07 μM
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Cytotoxicity against human Hs578T triple-negative breast cancer cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
Cytotoxicity against human Hs578T triple-negative breast cancer cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
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38892310 |
| MDA-MB-231 | IC50 |
4.64 μM
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Cytotoxicity against human MDA-MB-231-Luc triple-negative breast cancer cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
Cytotoxicity against human MDA-MB-231-Luc triple-negative breast cancer cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
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38892310 |
| MDA-MB-435S | IC50 |
3.25 μM
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Cytotoxicity against human MDA-MB-435S triple-negative breast cancer cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
Cytotoxicity against human MDA-MB-435S triple-negative breast cancer cells assessed as reduction in cell viability incubated for 24 hrs by CCK-8 assay.
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38892310 |
体外実験
Ibulocydine (0-50 μM; 18-24 h) dose-dependently inhibits the viability of SK-HEP-1, HepG2, and SNU-354 cells and suppresses DNA synthesis in SNU-354 cells[1].
Ibulocydine (0.1-50 μM; 24 h) inhibits Cdk7-mediated RNA polymerase II Ser-5 phosphorylation and Cdk9-mediated RNA polymerase II Ser-2 phosphorylation in SNU-354, SK-HEP-1, and HepG2 cells; the corresponding IC50 values in SNU-354 cells are 0.45 μM and 0.33 μM, respectively, with minimal effects on total RNA polymerase II levels[1].
Ibulocydine (50 μM; 6-12 h) inhibits Cdk1-mediated nucleolin phosphorylation by approximately 50% within 12 h and suppresses Cdk2-mediated Rb phosphorylation by about 50% within 6 h in human hepatocellular carcinoma SNU-354 cells[1].
Ibulocydine (10 μM; 6-24 h) time-dependently reduces the mRNA and protein levels of Mcl-1, survivin, and XIAP in SNU-354, SK-HEP-1, and HepG2 cells[1].
Ibulocydine (50 μM; 6 h) induces PARP cleavage (a marker of apoptosis) in SNU-354, SK-HEP-1, and HepG2 cells[1].
Ibulocydine (0.1-50 μM; 24 h) dose-dependently activates caspase-3 activity in SNU-354 cells[1].
Ibulocydine (10-50 μM; 12 h) increases the sub-G1 apoptotic cell population in SNU-354, SK-HEP-1, and HepG2 cells in a dose- and time-dependent manner, but has no effect on the sub-G1 cell population in normal mouse hepatocytes AML-12[1].
Ibulocydine (24 h) reduces the viability of Hs578T, MDA-MB-231-Luc, and MDA-MB-435S cells in a dose-dependent manner, with IC50 values of 3.07 μM, 4.64 μM, and 3.25 μM, respectively[2].
Ibulocydine (1-3 μM; 12 h exposure followed by 9 days of incubation) inhibits long-term colony formation in Hs578T, MDA-MB-231-Luc, and MDA-MB-435S cells[2].
Ibulocydine (0.25-3 μM; 24 h) induces dose-dependent increases in cleaved caspase-3 and cleaved PARP in Hs578T, MDA-MB-231-Luc, and MDA-MB-435S cells, and decreases the expression of anti-apoptotic proteins XIAP, Bcl-xL, survivin, and Mcl-1, as well as dose-dependent reductions in the protein levels of MMP-2, MMP-9, Snail 1/2, TWIST, and ZEB1[2].
Ibulocydine (3 μM; 24 h) induces apoptotic cell death in Hs578T, MDA-MB-231-Luc, and MDA-MB-435S cells[2].
Ibulocydine (50-100 nM; 24 h) sensitizes TRAIL-resistant human hepatocellular carcinoma cells Hep3B and SK-Hep1 to TRAIL-induced caspase-dependent apoptosis, and synergistic cell death is observed upon combined treatment[3].
Ibulocydine (0.05 μM) inhibits Cdk7/Cdk9 activity in Hep3B cells, and co-treatment with TRAIL induces apoptosis in Hep3B and SK-Hep1 cells through calpain-mediated Bax cleavage[3].
Ibulocydine (50-100 nM; 24 h) enhances the sensitivity of human hepatocellular carcinoma cells Hep3B and SK-Hep1 to TRAIL through calpain activation, which mediates Bax cleavage and subsequent caspase-dependent apoptosis[3].
Combined treatment with ibulocydine (50 nM; 24 h) and TRAIL induces apoptosis in human hepatoma Hep3B cells overexpressing Bcl-xL, and this effect is not blocked by Bcl-xL overexpression[3].
Ibulocydine (0.4-0.8 μM, 30 min followed by 10 Gy radiotherapy, with a total incubation time of 24 h) induces caspase-dependent apoptosis in human lung cancer A549 cells and human colon cancer RKO cells through the cleavage of caspase-3, caspase-9, and PARP[4].
Ibulocydine (0.1-1 μM; 16-24 h) inhibits RNA polymerase II phosphorylation at Ser-2 and Ser-5 sites and regulates Bcl-2 and Bax expression at the transcriptional level in a dose-dependent manner; in human lung cancer A549 cells and human colon cancer RKO cells, its combination with radiotherapy reduces the Bcl-2/Bax ratio[4].
Ibulocydine (1-3 μM; 24 h) inhibits the migration of Hs578T and MDA-MB-231-Luc cells in a dose-dependent manner; at (0.5-1 μM), it inhibits the migration of MDA-MB-435S cells[2].
Ibulocydine (0.5-1 μM; 24 h) inhibits the invasion of Hs578T, MDA-MB-231-Luc, and MDA-MB-435S cells in a dose-dependent manner[2].
Combined treatment with ibulocydine (50-100 nM; 24 h) and TRAIL induces apoptosis in Hep3B and SK-Hep1 human hepatocellular carcinoma cells through mitochondrial translocation of cleaved Bax, which mediates MMP loss and cytochrome c release[3].
Ibulocydine (0.4-0.8 μM; pretreatment for 30 min before 10 Gy radiotherapy, with a total incubation time of 24 h) induces significant mitochondrial dysfunction in human lung cancer A549 cells and human colon cancer RKO cells, including MMP loss and cytochrome c release, and its effect depends on the downregulation of Bcl-2 expression levels[4].
Ibulocydine (24 h) synergizes with radiotherapy to reduce the viability of A549, RKO, Hep3B, and MCF-7 cells; among these, the viability inhibitory effect begins at 1 μM in A549 cells and at concentrations above 0.8 μM in RKO cells[4].
Ibulocydine (0.4-0.8 μM; pretreatment for 30 min before 10 Gy radiotherapy, with a total incubation time of 24 h) increases sub-G1 cell accumulation in human lung cancer A549 cells and human colon cancer RKO cells[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human HCC SNU-354, SK-HEP-1, HepG2 cells
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Concentration:0.1, 0.5, 1, 5, 10, 50 μM (24 h incubation); 10 μM (6, 12, 18, 24 h incubation)
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Incubation Time:24 h (0.1-50 μM); 6-24 h (10 μM)
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Result:Inhibited Cdk7-mediated Ser-5 phosphorylation of RNA polymerase II with an IC50 of 0.45 μM in SNU-354 cells.
Inhibited Cdk9-mediated Ser-2 phosphorylation of RNA polymerase II with an IC50 of 0.33 μM in SNU-354 cells, with greater potency than comparison compounds.
Reduced Ser-5 and Ser-2 phosphorylation in a time-dependent manner in SK-HEP-1 and HepG2 cells, with greater efficacy than parent compound BMK-Y101.
Left total RNA polymerase II levels minimally affected.
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Cell Line:human HCC SNU-354, SK-HEP-1, HepG2 cells, mouse normal hepatocyte AML-12 cells
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Concentration:0.1, 0.5, 1, 5, 10, 50 μM (24 h incubation); 50 μM (6, 12, 18, 24 h incubation); 10, 50 μM (12 h incubation)
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Incubation Time:24 h (0.1-50 μM); 6-24 h (50 μM); 12 h (10-50 μM)
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Result:Increased the sub-G1 population in dose- and time-dependent manners in SNU-354 cells, with greater efficacy than parent compound BMK-Y101.
Increased the sub-G1 population in SK-HEP-1, HepG2, and SNU-354 cells after treatment with 10 or 50 μM for 12 h.
Caused no increase in the sub-G1 population in AML-12 normal hepatocyte cells.
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Cell Line:human TNBC cell lines Hs578T, MDA-MB-231-Luc, and MDA-MB-435S
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Concentration:1 μM, 3 μM
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Incubation Time:12 h exposure followed by 9 days of incubation
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Result:Inhibited long-term survival by reducing the number of colonies formed in all three TNBC cell lines.
Showed greater inhibition at the 3 μM dose compared to the 1 μM dose.
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Cell Line:human TNBC cell lines Hs578T, MDA-MB-231-Luc, and MDA-MB-435S
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Concentration:0.25 μM, 0.5 μM, 1 μM, 3 μM
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Incubation Time:24 h
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Result:Increased cleavage levels of caspase-3 and PARP in a dose-dependent manner.
Reduced protein levels of anti-apoptotic proteins XIAP, Bcl-xL, survivin, and Mcl-1 in a dose-dependent manner.\nReduced protein levels of MMP-2, MMP-9, and mesenchymal markers Snail 1/2, TWIST, and ZEB1 in a dose-dependent manner across all three TNBC cell lines.
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Cell Line:human TNBC cell lines Hs578T, MDA-MB-231-Luc, and MDA-MB-435S
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Concentration:0.5 μM, 1 μM
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Incubation Time:24 h
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Result:Significantly reduced the number of invading cells in a dose-dependent manner across all three TNBC cell lines.
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Cell Line:A549 cells, RKO cells
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Concentration:0.8 μM (A549 cells); 0.4 μM (RKO cells)
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Incubation Time:30 min pretreatment before 10 Gy radiotherapy; 24 h total incubation
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Result:Did not increase sub-G1 phase cell accumulation when used alone.
Did not increase sub-G1 phase cell accumulation when radiotherapy was used alone.
Significantly increased sub-G1 phase cell accumulation in both A549 and RKO cells when combined with radiotherapy.
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Cell Line:A549 cells, RKO cells
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Concentration:0.8 μM (A549 cells); 0.4 μM (RKO cells)
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Incubation Time:30 min pretreatment before 10 Gy radiotherapy; 24 h total incubation
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Result:Induced only small amounts of Annexin V-positive cells when used alone.
Induced only small amounts of Annexin V-positive cells when radiotherapy was used alone.
Markedly increased Annexin V-positive cells, reaching ~20% in both A549 and RKO cells, when combined with radiotherapy.
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Cell Line:A549 cells, RKO cells
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Concentration:0.8 μM (A549 cells); 0.4 μM (RKO cells)
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Incubation Time:30 min pretreatment before 10 Gy radiotherapy; 24 h total incubation
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Result:Did not induce cleavage of caspase-3, caspase-9, or PARP when used alone.
Did not induce cleavage of caspase-3, caspase-9, or PARP when radiotherapy was used alone.
Induced cleavage of caspase-3, caspase-9, and PARP in both A549 and RKO cells when combined with radiotherapy, while precursor levels of caspase-8 remained unchanged.
Blocked cell death induced by the combined treatment when pre-treated with the pan-caspase inhibitor zVAD-fmk.
体内実験
Ibulocydine (100 μg per mouse; intrathecal injection; once every 3 days for a total of 3 doses) combined with radiotherapy significantly delays tumor growth in A549 xenograft mice, accompanied by decreased Bcl-2 expression, without causing body weight loss[4].
Ibulocydine (3 µM; in vitro pretreatment; 6 h) inhibits lung metastasis of triple-negative breast cancer cells in a mouse model, as evidenced by persistently lower total flux of luciferase at day 56 and reduced tumor burden in the lungs[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:athymic nude mice (male, 5-6 weeks old, subcutaneous xenograft of SNU-354 human HCC cells)[1]
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Dosage:4 mg/kg; 20 mg/kg
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Administration:i.p.; five times weekly; 3 weeks
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Result:Suppressed SNU-354 xenograft growth by 15% at 4 mg/kg.
Suppressed SNU-354 xenograft growth by 47% at 20 mg/kg.
Induced apoptosis in xenografted HCC cells in a dose-dependent manner.
Caused no change in body weight.
Detected no apoptosis in normal liver tissues.
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Animal Model:BALB/c nude mice (female, 6 weeks old, experimental lung metastasis model via intravenous injection of MDA-MB-231-Luc cells)[2]
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Dosage:3 µM
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Administration:in vitro pretreatment; 6 h
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Result:Maintained luciferase total flux near baseline throughout 56-day observation period.
Reduced lung tumor burden markedly at study endpoint compared to control mice.
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Animal Model:Balb/c nude (male, 5-week old)[4]
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Dosage:100 μg/mouse
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Administration:i.t.; 3 times at 3-day intervals; administered 2 hours prior to radiotherapy
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Result:Induced marked tumor growth delay, with tumor growth almost halted for 15 days.
Showed no body weight loss.
Reduced Bcl-2 protein levels significantly in tumor specimens compared to controls.
化学情報
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CAS 番号 1314096-68-8
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分子量 458.26
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分子式 C16H20BrN5O6
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SMILES
O=C(C(C)C)OC[C@H]1[C@@H](O)[C@H](O)[C@@H](N2C3=NC(Br)=C(C3=C(N)N=C2)C(N)=O)O1
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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)
Ibulocydine 関連分類
HY-116054 関連分類
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