UNC1666
UNC1666 is an ATP-competitive dual-target Mer/Flt3 tyrosine kinase inhibitor with IC50 values of 0.55 nM and 0.69 nM, and Ki values of 0.16 nM and 0.67 nM, respectively. UNC1666 reduces the phosphorylation levels of Mer and Flt3, suppresses downstream pro-survival signaling pathways (Erk1/2, Akt and Stat), induces cell apoptosis, and decreases colony formation of acute myeloid leukemia cells. UNC1666 is applicable to research related to acute myeloid leukemia.
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- CAS. Nr.: 1429882-12-1
- Formel: C26H35N5O4S
- Molecular Weight:513.66
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
Beschreibung
In Vitro
UNC1666 (Analogue 2) exhibits subnanomolar to low nanomolar in vitro inhibitory activity against Mer, Flt3, Axl (29 nM) and Tyro3 (37 nM) kinases, with the most potent activity against Flt3 (0.69 nM) and Mer (0.93 nM)[1].
UNC1666 (10-300 nM) inhibits Mer phosphorylation in Kasumi-1 AML cells in a concentration-dependent manner, and potently suppresses Flt3 phosphorylation in MV4;11 Flt3-ITD AML cells[2].
UNC1666 (50-300 nM) dose-dependently inhibits the downstream pro-survival signaling pathways (Erk1/2, Akt, and Stat) in Mer-positive Kasumi-1 cells and Flt3-ITD MV4;11 AML cells following 2 h of treatment, with stronger activity observed in Flt3-ITD cells[2].
UNC1666 (10-300 nM; 72 h) induces apoptosis in Mer-positive and Flt3-ITD AML cell lines in a dose-dependent manner after 72 hours of treatment[2].
UNC1666 (50-300 nM; 72 h) inhibits the long-term rebound growth of Kasumi-1 and MV4;11 acute myeloid leukemia (AML) cells even after the completion of treatment[2].
UNC1666 (10-300 nM; 72 h) significantly reduces the colony-forming ability of Mer-positive and Flt3-ITD AML cell lines cultured in soft agar[2].
UNC1666 (50-300 nM; 2 h) dose-dependently inhibits the phosphorylation of Mer and Flt3 in primary AML blasts co-expressing Mer and Flt3ITD, suppresses downstream pro-survival signaling pathways (Erk1/2, Akt, Stat5) in the cells, induces cellular apoptosis, and reduces colony-forming ability[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Mer-positive (Kasumi-1, NOMO-1) and Flt3-ITD (MV4;11, MOLM-13) AML cell lines
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Concentration:10, 25, 50, 100, 300nM
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Incubation Time:72 h
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Result:Induced apoptosis in 50-67% of Mer-positive cells at 100 nM, and 68-76% of Mer-positive cells at 300 nM, with Kasumi-1 cells showing 76% apoptotic/dead cells at 300 nM.
Induced apoptosis in 54-67% of Flt3-ITD cells at 50 nM, and 90-98% of Flt3-ITD cells at 300 nM, with MV4;11 cells showing 90% apoptotic/dead cells at 300 nM and MOLM-13 cells showing 98% apoptotic/dead cells at 300 nM.
Confirmed increased cleavage of PARP and Caspase-3 in a dose-dependent manner via immunoblot.
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Cell Line:Mer-positive (Kasumi-1) and Flt3-ITD (MV4;11) AML cell lines
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Concentration:50, 100, 300nM
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Incubation Time:72 h (initial treatment)
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Result:Resulted in only a 2.5-fold increase in viable cell number over 6 days in Kasumi-1 cells at 100 nM, compared to a 14-fold increase with vehicle.
Resulted in only a 13-fold increase in viable cell number over 6 days in MV4;11 cells at 50 nM, compared to a 67-fold increase with vehicle.
Caused more striking proliferation defects at higher concentrations, with minimal viable cells at Day 6.
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Cell Line:Mer-positive (Kasumi-1, NOMO-1) and Flt3-ITD (MV4;11, MOLM-13) AML cell lines
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Concentration:10, 25, 50, 100, 300nM
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Incubation Time:Continuous treatment, medium renewed twice weekly (14-21 days total)
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Result:Reduced Kasumi-1 cell colony formation by 90% at 100 nM.
Reduced NOMO-1 cell colony formation by 71% at 100 nM.
Reduced MV4;11 cell colony formation by 61% at 50 nM.
Reduced MOLM-13 cell colony formation by 93% at 50 nM.
Chemical Information
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CAS. Nr. 1429882-12-1
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Molecular Weight 513.66
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Formel C26H35N5O4S
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SMILES
N(CCCC)C=1N=C2C(C(=CN2[C@H]3CC[C@H](O)CC3)C4=CC=C(S(=O)(=O)N5CCOCC5)C=C4)=CN1
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[1]. Zhang W, et al. UNC2025, a potent and orally bioavailable MER/FLT3 dual inhibitor. J Med Chem. 2014;57(16):7031-7041. [Content Brief]
[2]. Lee-Sherick AB, et al. Efficacy of a Mer and Flt3 tyrosine kinase small molecule inhibitor, UNC1666, in acute myeloid leukemia. Oncotarget. 2015;6(9):6722-6736. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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