BLU-654
BLU-654 is an orally active antineoplastic agent and KIT inhibitor. BLU-654 is a highly selective inhibitor targeting wild-type KIT, PDGFRβ, and KITV654A over most other kinases in the kinome. BLU-654 exerts sustained antineoplastic activity in KITV654A cell-derived xenograft mouse models. BLU-654 can be used in research related to Imatinib (HY-15463)-resistant gastrointestinal stromal tumors.
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- CAS No.: 2999638-62-7
- Formule: C21H28FN7O2
- Masse moléculaire:429.49
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
BLU-654 potently inhibits the autophosphorylation of KIT in HMC1.1 11/13 cells, with an IC50 of 5.7 nM[1].
BLU-654 inhibits the autophosphorylation of wild-type KIT in M-07e cells with an IC50 of 82.7 nM, and is 15-fold more selective for KITV654A than for wild-type KIT[1].
BLU-654 inhibits the autophosphorylation of PDGFRβ in SW569 cells with an IC50 of 1251.4 nM, and is 219-fold more selective for KITV654A than for PDGFRβ[1].
BLU-654 exhibits species-dependent metabolic stability, with no intrinsic clearance in human and canine liver microsomes, low clearance (2 mL·min-1·kg-1) in human hepatocytes, and higher clearance in rat, canine and cynomolgus monkey hepatocytes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID mice[1]
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Dosage:1-30 mg/kg (PK/PD); 3-60 mg/kg (Efficacy)
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Administration:p.o.; daily; 27 days (Efficacy); single dose (PK/PD)
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Result:Elicited a dose- and time-dependent reduction in pSTAT5, with a free in vivo IC50 of 4.2 nM at 4 hours.
Reduced pSTAT5 by 95% over 4 hours at 10 mg/kg, with levels returning to 68% of baseline at 24 hours.
Achieved dose-dependent plasma exposures, exceeding the in vitro pKIT IC50 at most doses 10 hours postdosing, and at 30 mg/kg, exposures remained above the in vitro IC50 for up to 24 hours.
Showed slower tumor growth in mice treated with 3 mg/kg compared to controls after 27 days of daily dosing.
Eliminated tumors in mice treated with 10, 30, and 60 mg/kg, with no tumor regrowth observed during the 48-day post-treatment observation period.
Maintained body weight within 10% of baseline across all doses, indicating good tolerability.
Chemical Information
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CAS No. 2999638-62-7
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Masse moléculaire 429.49
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Formule C21H28FN7O2
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SMILES
F[C@@H](C)C1=NC(N)=CC(NC2=NC=C(C3=CN(CC(C)(O)C)N=C3)C(OC(C)C)=C2)=N1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
BLU-654 Related Classifications
HY-182043 Related Classifications
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