ON044580
Based on 1 Customer Validation
ON044580 is a non–ATP-competitive JAK2 and BCR-ABL kinases inhibitor. ON044580 inhibits wild-type (WT) and V617F mutant JAK2 with IC50 values of 1.23 μM, 1.09 μM, respectively. ON044580 also inhibits both WT and T315I mutant BCR-ABL kinases., ON044580 blocks the IL-3–mediated phosphorylation of JAK2 and STAT5, induces apoptosis in Imatinib (HY-15463)-resistant chronic myeloid leukemia (CML). ON044580 can be used for the study of CML, myelodysplasia (MDS) and other myeloproliferative neoplasms.
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- 純度: 99.11%
- CAS 番号: 1035199-04-2
- 分子式: C23H15BrFNO5S
- 分子量:516.34
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保管条件:
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
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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Help & FAQs
生物活性
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JAK2-WT 1.23 μM (IC50) |
JAK2-V617F 1.09 μM (IC50) |
WT BCR-ABL |
T315I-BCR-ABL |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| K562 | GI50 |
< 1 μM
Compound: 6c
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Growth inhibition of human K562 cells expressing p210Bcr/Abl after 96 hrs by trypan blue exclusion assay.
Growth inhibition of human K562 cells expressing p210Bcr/Abl after 96 hrs by trypan blue exclusion assay.
|
20188579 |
| DU-145 | GI50 |
1 μM
Compound: 6c
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Growth inhibition of human DU145 cells after 96 hrs by trypan blue exclusion assay.
Growth inhibition of human DU145 cells after 96 hrs by trypan blue exclusion assay.
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20188579 |
| K562 | IC50 |
0.5 μM
Compound: 6c
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Inhibition of BCR/ABL p210 autophosphorylation in human K562 cells after 2 hrs by Western blot analysis.
Inhibition of BCR/ABL p210 autophosphorylation in human K562 cells after 2 hrs by Western blot analysis.
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20188579 |
| HEL | GI50 |
0.9 μM
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Inhibits the proliferation of HEL cells.
Inhibits the proliferation of HEL cells.
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20717479 |
| SET-2 | GI50 |
3.0 μM
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Inhibits the proliferation of SET-2 cells.
Inhibits the proliferation of SET-2 cells.
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20717479 |
| K562 | IC50 |
7.94 μM
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Inhibition of BCR-ABL kinase activity.
Inhibition of BCR-ABL kinase activity.
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20717479 |
ON044580 (0.25-10 μM; 30 min) inhibits recombinant wild-type JAK2 and JAK2-V617F kinase activities with IC50 values of 1.23 μM and 1.09 μM, respectively[1].
ON044580 (0-10 μM; 30 min) inhibits full-length JAK2 immunoprecipitated from Ba/F3:JAK2V617F cells with an IC50 of approximately 4 μM[1].
ON044580 (0-20 μM; 30 min) inhibits wild-type BCR-ABL and T315I mutant BCR-ABL kinase activities immunoprecipitated from K562 and 32D:p210T315I cells, with IC50 values of 7.94 μM and 2.08 μM, respectively[1].
ON044580 (0-20 μM; 2 h) inhibits JAK2 autophosphorylation and STAT5 phosphorylation in IL-3-stimulated Ba/F3:JAK2V617F cells in a concentration-dependent manner[1].
ON044580 (10 μM; 15-60 min) inhibits IL-3-mediated JAK2 phosphorylation within 15-30 minutes in Ba/F3:JAK2V617F cells[1].
ON044580 (0-10 μM; 2 h) inhibits STAT3 phosphorylation in U266 multiple myeloma cells (constitutive IL-6 receptor/JAK2/STAT3 pathway) in a dose-dependent manner[1].
ON044580 (0.5-10 μM; 72 h) inhibits the proliferation of JAK2V617F-expressing cells (Ba/F3:JAK2V617F, HEL, SET-2) with GI50 values of 0.25 μM, 0.9 μM, and 3.0 μM, respectively[1].
ON044580 (0.5 μM; 2-24 h) induces PARP cleavage in Ba/F3:JAK2V617F cells at 24 h[1].
ON044580 (0.1-0.5 μM; ex vivo, 48 h) selectively reduces aneuploid (monosomy 7) cells while maintaining/increasing diploid cells in bone marrow mononuclear cells[1].
ON044580 (1-10 μM; 2 h short-term exposure followed by 96 h recovery) inhibits growth of Ba/F3:JAK2V617F, HEL, and K562 cells in a concentration-dependent manner, while normal mouse bone marrow cells remain unaffected[1].
ON044580 (0.5-10 μM; ex vivo, 48 h) induces apoptosis in primary CML cells from blast crisis patients refractory to Imatinib (HY-15463)[1][2].
ON044580 (0.25-10 μM; 30 min) inhibits recombinant Abl kinase activity by 50% at 5 μM and 75% at 10 μM[2].
ON044580 (0.1-10 μM; 16 h) reduces BCR-ABL protein levels and pTyr-JAK2 in Imatinib-sensitive and Imatinib-resistant (T315I, E255K) BCR-ABL+ cells in a dose-dependent manner[2].
ON044580 (10 μM; 6-16 h) reduces levels of BCR-ABL downstream signaling molecules including STAT3, pTyr705-STAT3, pSer727-STAT3, and Akt in BCR-ABL+ 32D cells[2].
ON044580 (0-10 μM; 16 h) reduces HSP90α transcript levels in BCR-ABL+ 32D cells[2].
ON044580 (0.25-10 μM; 16 h) reduces HSP90 protein levels in Imatinib-sensitive and Imatinib-resistant (T315I, E255K) BCR-ABL+ cells[2].
ON044580 (10 μM; 3 h) disrupts the BCR-ABL/JAK2/HSP90 high molecular weight network complex in BCR-ABL+ 32D cells[2].
ON044580 (0-10 μM; 48 h) induces apoptosis in Imatinib-sensitive and Imatinib-resistant (T315I, K562-R) BCR-ABL+ cells at concentrations of 1-5 μM[2].
ON044580 (0.1-0.5 μM; 2 weeks) inhibits colony formation of Imatinib-sensitive and Imatinib-resistant (T315I, E255K) BCR-ABL+ cells in soft agar[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Ba/F3:JAK2V617F cells (+IL-3)
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Concentration:0.1, 0.5, 1, 5, 10 μM
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Incubation Time:2 h
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Result:Inhibited JAK2 autophosphorylation and STAT5 phosphorylation in a concentration-dependent manner.
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Cell Line:Ba/F3:JAK2V617F cells (+IL-3)
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Concentration:10 μM
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Incubation Time:15-60 min
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Result:Inhibited IL-3-mediated JAK2 phosphorylation within 15-30 minutes.
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Cell Line:Ba/F3:JAK2V617F, HEL, SET-2 cells
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Concentration:0.5, 1, 2.5, 5, 10 μM
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Incubation Time:72 h
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Result:Inhibited the proliferation of JAK2V617F-expressing cells (Ba/F3:JAK2V617F, HEL, SET-2) with GI50 values of 0.25 μM, 0.9 μM, and 3.0 μM, respectively.
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Cell Line:Ba/F3:JAK2V617F
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Concentration:0.5 μM
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Incubation Time:2-24 h
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Result:Induced PARP cleavage.
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Cell Line:BCR-ABL+ 32D cells
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Concentration:10 μM
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Incubation Time:6-16 h
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Result:Reduces levels of BCR-ABL downstream signaling molecules including STAT3, pTyr705-STAT3, pSer727-STAT3, and Akt.
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Cell Line:BCR-ABL+ 32D cells
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Concentration:1, 5, 10 μM
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Incubation Time:16 h
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Result:Reduced HSP90 protein levels.
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Cell Line:BCR-ABL+ 32D cells
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Concentration:1, 5, 10 μM
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Incubation Time:16 h
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Result:Reduced HSP90α transcript levels.
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Cell Line:BCR-ABL+ cells (WT, T315I, K562-R)
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Concentration:2.5, 5, 10 μM
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Incubation Time:48 h
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Result:Induced apoptosis in Imatinib-sensitive and Imatinib-resistant (T315I, K562-R) BCR-ABL+ cells.
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Cell Line:BCR-ABL+ cells (WT, T315I, E255K)
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Concentration:0.01, 0.05, 0.1, 0.5, 1 μM
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Incubation Time:2 weeks
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Result:Inhibited colony formation.
化学情報
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CAS 番号 1035199-04-2
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性状 Solid
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分子量 516.34
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分子式 C23H15BrFNO5S
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Color Off-white to light yellow
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SMILES
O=C(C1=CC=C(C(O)=O)C=C1)/C(SCC2=CC=C(Br)C=C2)=C\C3=CC=C(F)C([N+]([O-])=O)=C3
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
純度とドキュメンテーション
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データシート (284 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Jatiani SS, et al. A Non-ATP-Competitive Dual Inhibitor of JAK2 and BCR-ABL Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition. Genes Cancer. 2010 Apr;1(4):331-45. [Content Brief]
[2]. Samanta AK, et al. Destabilization of Bcr-Abl/Jak2 Network by a Jak2/Abl Kinase Inhibitor ON044580 Overcomes Drug Resistance in Blast Crisis Chronic Myelogenous Leukemia (CML). Genes Cancer. 2010 Apr;1(4):346-59. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
ON044580 関連分類
HY-164393 関連分類
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