Syk/HDAC6-IN-1
Syk/HDAC6-IN-1 is a dual SYK/HDAC6 selective inhibitor with IC50 values of 0.19 nM (SYK) and 0.66 nM (HDAC6). Syk/HDAC6-IN-1 downregulates p-SYK to block downstream AKT/FOXO1 signaling, elevates acetylated histone H3 and α-tubulin via HDAC suppression, represses SREBF1 -mediated lipid biosynthetic pathways, triggers G0/G1 cell cycle arrest and robust mitochondrial-dependent caspase-3-mediated apoptosis in leukemia cells. Syk/HDAC6-IN-1 can be used for the research of FLT3-mutant acute myeloid leukemia.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C27H28N8O3
- 分子量:512.56
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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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生物活性
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HDAC6 0.66 nM (IC50) |
Syk 0.19 nM (IC50) |
HDAC1 3.39 nM (IC50) |
HDAC2 4.26 nM (IC50) |
HDAC3 7.55 nM (IC50) |
Caspase 3 |
FOXO1 |
α-Tubulin |
Syk/HDAC6-IN-1 (Compound 14) exhibits significant SYK inhibitory activity with an IC50 of 0.19 nM[1].
Syk/HDAC6-IN-1 (48 h) suppresses proliferation of MV4-11 cells bearing FLT3-ITD mutations, with an IC50 of 0.11 μM[1].
Syk/HDAC6-IN-1 displays potent and preferential inhibitory activity toward HDAC6 with an IC50 of 0.66 nM, while it also inhibits HDAC1 (IC50=3.39 nM), HDAC2 (IC50=4.26 nM), and HDAC3 (IC50=7.55 nM) at low nanomolar concentrations[1].
Syk/HDAC6-IN-1 (0.5-2.5 μM; 24 h) effectively inhibits SYK activation and modulates HDAC inhibition-associated biomarkers in MV4-11 cells[1].
Syk/HDAC6-IN-1 binds tightly to the SYK pocket via extensive polar and nonpolar interactions[1].
Syk/HDAC6-IN-1 is highly selective for SYK, only weakly inhibiting FLT1, SLK, JAK2 and LCK among 60 tested kinases[1].
Syk/HDAC6-IN-1 occupies the catalytic tunnel of HDAC6 and establishes hydrogen bonds, hydrophobic contacts and catalytic zinc coordination[1].
Syk/HDAC6-IN-1 (0.25-1 μM; 24 h) fails to induce cell cycle arrest in MV4-11 cells, primarily driving apoptosis via mitochondrial membrane potential loss and caspase-3 cleavage while displaying moderate autophagy-inducing capacity[1].
Syk/HDAC6-IN-1 (0.5 μM; 48 h) effectively represses cholesterol and fatty acid metabolism at the transcriptomic level in MV4-11 cells[1].
Syk/HDAC6-IN-1 (0.25-1 μM; 24 h) dose-dependently reduces SREBF1 mRNA and inhibits lipogenic signaling in MV4-11 cells[1].
Syk/HDAC6-IN-1 (0.25-1 μM; 24 h) suppresses AKT activation, reduces FOXO1 phosphorylation and thereby activates FOXO1 in MV4-11 cells[1].
Syk/HDAC6-IN-1 (10-20 μM; 24 h) dose-dependently impairs endothelial tube formation and migration in HUVEC[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 cells
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Concentration:0.5 μM, 1 μM, 2.5 μM
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Incubation Time:24 h
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Result:Significantly reduced the p-SYK/total SYK ratio.
Increased acetylation levels of α-tubulin and histone H3 (biomarkers associated with HDAC inhibition).
Significantly increased acetylation levels on the ninth lysine of histone H3 (Ac-H3K9).
Significantly increased the cleaved caspase-3/total caspase-3 ratio.
Reduced P62 protein levels in a dose-dependent manner.
Increased LC3-II accumulation and a higher LC3-II/LC3-I ratio.
Reduced the level of p-AKT protein.
Reduced the level of p-FOXO1 protein.
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Cell Line:MV4-11 cells
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Concentration:0.25 μM, 0.5 μM, 1 μM
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Incubation Time:24 h
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Result:Failed to induce obvious cell cycle arrest, with no notable S/G2/M cell accumulation detected.
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Cell Line:MV4-11 cells
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Concentration:0.25 μM, 0.5 μM, 1 μM
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Incubation Time:24 h
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Result:Elevated apoptotic cell populations in a significant, dose-dependent manner.
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Cell Line:MV4-11 cells
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Concentration:0.5 μM, 1 μM, 2.5 μM
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Incubation Time:24 h
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Result:Triggered dose-dependent nuclear morphological changes such as chromatin condensation and fragmentation.
Concentration-dependently diminished mitochondrial fluorescence and impaired mitochondrial function.
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Cell Line:MV4-11 cells
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Concentration:0.25 μM, 0.5 μM, 1 μM
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Incubation Time:24 h
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Result:Dose-dependently reduced SREBF1 mRNA levels.
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Cell Line:HUVEC
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Concentration:10 μM, 20 μM
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Incubation Time:24 h
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Result:Dose-dependently impaired endothelial migration and vascular-like tube formation.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | MRT0-inf | Bioavailability |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.p. | 275.02 min | 120 min | 14.6 ng/mL | 6144.6 min·ng/mL | 418.44 min | 81.28 % |
| Mice[1] | 1 mg/kg | i.v. | 370.32 min | 60 min | 17.55 ng/mL | 7559.45 min·ng/mL | 516.44 min | 100 % |
| Mice[1] | 50 mg/kg | o.a. | 416.82 min | 240 min | 123.95 ng/mL | 74638.5 min·ng/mL | 659.33 min | 19.74 % |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:6-week-old male BALB/c nude mice (CAnN.Cg-Foxn1nu/Crl) subcutaneously implanted with MV4-11 cells[1]
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Dosage:25 mg/kg, 50 mg/kg
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Administration:i.p., once daily, for 24 days
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Result:Significantly inhibited tumor size.
Significantly reduced tumor weight by approximately 80% at a dose of 50 mg/kg.
Did not have a significant effect on mouse body weight.
Dose-dependently reduced p-SYKY323 levels and elevated Ac-H3K9 levels.
Showed a significantly reduced p-SYK/SYK ratio at a dose of 50 mg/kg.
Induced a concentration-dependent increase in histone H3K9 acetylation levels, consistent with HDAC inhibition.
Did not affect serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), creatine phosphokinase (CPK), and creatinine (CRE).
Did not cause any significant morphological changes in the heart, liver, spleen, lungs, or kidney tissues.
化学情報
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分子量 512.56
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分子式 C27H28N8O3
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SMILES
O=C(NC1=CC=C(NC2=NC(C3=CC4=C(C=C3)C=NN4)=CN5C2=NC=C5)C=C1)CCCCCCC(NO)=O
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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)
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