ON012380
ON012380 is a kinase inhibitor with an IC50 of 9 nM against BCR-ABL. As a substrate-competitive BCR-ABL inhibitor, ON012380 binds to a non-ATP site, and inhibits the kinase activities of PDGFR, Fyn and LynB at higher concentrations. ON012380 induces apoptosis, inhibits STAT-5 phosphorylation, reduces cell viability and suppresses cell growth in leukemia cells. ON012380 can be used in the research of chronic myeloid leukemia and Imatinib (HY-15463)-resistant chronic myeloid leukemia.
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- CAS No.: 592543-24-3
- 화학식: C22H27NO8S
- 분자량:465.52
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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
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Bcr-Abl 9 nM (IC50) |
PDGFR |
Fyn |
LynB |
STAT5 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| DU-145 | IC50 |
0.025 μM
Compound: 27d
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Cytotoxicity against human DU145 cells after 96 hrs by trypan blue exclusion assay
Cytotoxicity against human DU145 cells after 96 hrs by trypan blue exclusion assay
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[PMID: 21812421] |
| K562 | IC50 |
0.015 μM
Compound: 27d
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Cytotoxicity against human K562 cells after 96 hrs by trypan blue exclusion assay
Cytotoxicity against human K562 cells after 96 hrs by trypan blue exclusion assay
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[PMID: 21812421] |
In Vitro
ON012380 (1 nM-1 μM; 30 min pre-incubation, 20 min kinase reaction) potently inhibits wild-type BCR-ABL kinase activity with an IC50 of 9.0 nM, and acts synergistically with Imatinib (HY-15463) to reduce the IC50 to 0.83 nM[1].
ON012380 (0.1 nM-1000 nM; 30 min pre-incubation, 20 min kinase reaction) acts as a substrate-competitive inhibitor of wild-type BCR-ABL, with IC50 values unaffected by ATP concentration but increased by higher Crk substrate concentrations[1].
ON012380 (30 min pre-incubation, 20 min kinase reaction) potently inhibits the kinase activity of the Imatinib-resistant BCR-ABLT315I mutant with an IC50 of 1.5 nM[1].
ON012380 (72 h) reduces viability of K562 and 32Dcl3-p210BCR-ABL cells with an LD50 of 10-15 nM[1].
ON012380 (10 nM-1000 nM; 24 h) dose-dependently inhibits BCR-ABL kinase activity and suppresses STAT-5 phosphorylation in K562 cells[1].
ON012380 (72 h) reduces viability of all tested Imatinib-resistant BCR-ABL mutant-expressing 32Dcl3 cell lines with LD50 values ranging from 5.9 nM to 10.0 nM[1].
ON012380 (1 nM-1000 nM; 24 h) dose-dependently inhibits BCR-ABLT315I kinase activity and suppresses STAT-5 phosphorylation in 32Dcl3-BCR-ABLT315I cells[1].
ON012380 potently inhibits growth of cells expressing wild-type Bcr-Abl and all tested Imatinib-resistant Bcr-Abl mutants (including BCR-ABLT315I) at concentrations < 10 nM, and also inhibits PDGFR- and Lyn-dependent cell proliferation with an IC50 of approximately 80 nM[2].
ON012380 (1.38-9 nM) potently inhibits wild-type Bcr-Abl kinase activity with an IC50 of 9 nM and the Imatinib-resistant Bcr-AblT315I mutant with an IC50 of 1.38 nM via non-ATP competitive binding[3].
ON012380 (<10 nM) induces apoptosis and cell death in Ph+ CML cells expressing the Imatinib-resistant BCR-ABLT315I isoform[3].
ON012380 (2-24 h) reduces viability and induces apoptosis in IL-3-dependent BaF3 cells, wild-type BCR-ABL-transformed BaF3 cells, and BCR-ABLT315I-mutant BCR-ABL-transformed BaF3 cells, with no significant inhibition of BCR-ABL signaling (Stat5 and CrkL phosphorylation)[4].
ON012380 reduces viability with an IC50 of ~300 nM and induces apoptosis in K562, BV-173, and T315I-mutant BCR-ABL-expressing BV-173R CML cells, but has limited activity in Lyn-overexpressing K562R cells, with no associated inhibition of BCR-ABL or Lyn kinase signaling[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:K562 cells
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Concentration:10 nM; 100nM; 1000nM
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Incubation Time:24 h
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Result:Inhibited BCR-ABL kinase activity in a dose-dependent manner.
Inhibited STAT-5 phosphorylation.
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Cell Line:32Dcl3-BCR-ABLT315I cells
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Concentration:1 nM; 10 nM; 100nM; 1000nM
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Incubation Time:24 h
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Result:Inhibited BCR-ABLT315I kinase activity in a dose-dependent manner.
Inhibited STAT-5 phosphorylation.
In Vivo
ON012380 (100 mg/kg; i.p.; daily; 21 days) produces significant growth inhibition of Bcr-AblT315I-positive leukemias in nude mice without causing hematoxicity[3].
ON012380 (200 mg/kg; i.v.; single dose) does not impair normal hematopoietic colony formation in CD-1 mice[1].
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 (female, ncr-ncr, injected i.v. with 1×106 32Dcl3 cells expressing Imatinib-resistant BCR-ABL T315I mutant)[1]
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Dosage:100 mg/kg (efficacy); 200 mg/kg (7-day safety); 300 mg/kg (single-dose safety)
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Administration:i.p.; daily; up to 21 days (100 mg/kg, 200 mg/kg); i.v.; single dose (300 mg/kg)
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Result:Reduced the average number of T315I leukemic cells per 10 blood fields on days 7 and 14 compared to vehicle- and Imatinib-treated groups.
Showed no signs of toxicity, including no body weight loss, ruffled coats, lethargy, or abnormal feces.
Was well tolerated at 100 mg/kg daily i.p. for up to 21 days.
Produced no toxicity at a single 300 mg/kg dose.
Was well tolerated at 200 mg/kg daily dosing for 7 days.
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Animal Model:CD-1 mice[1]
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Dosage:200 mg/kg
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Administration:i.v.; single dose
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Result:Showed no reduction in colony formation for erythroid (BFU-E), granulocyte (CFU-G), macrophage (CFU-M), granulocyte-macrophage (CFU-GM), or pre-B lymphocyte lineages compared to control mice.
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Animal Model:Nude mice[3]
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Dosage:100 mg/kg
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Administration:i.p.; daily; 21 days
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Result:Induced significant growth inhibition of T315I leukemias.
Caused no hematoxicity during daily dosing over 3 weeks at doses >100 mg/kg.
- Western Blot
- Mammalian live/dead viability and cytotoxicity staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- Somatic Cell Culture
- CCK-8/WST-8 Cell Proliferation Assay
- Cell Counting-Based Growth Curve Assay
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Cell Cytotoxicity Assay
- Protocol for Cell Counting and Cell Density Analysis
- Apoptosis Solutions
- Protocol for Kinase activity and phosphorylation assays
- MTT Cell Proliferation Assay
Chemical Information
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CAS No. 592543-24-3
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분자량 465.52
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화학식 C22H27NO8S
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SMILES
C(=C/S(CC1=CC(N[C@H](C(O)=O)C)=C(OC)C=C1)(=O)=O)\C2=C(OC)C=C(OC)C=C2OC
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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)
ON012380 Related Classifications
HY-10365 Related Classifications
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