LTK-14A
LTK-14A, a derivative of Garcinol (HY-107569), is an orally effective selective inhibitor of histone butyrylation. LTK-14A selectively inhibits butyrylation without affecting acetylation by interacting with the C1438 residue in the catalytic domain of p300. LTK-14A significantly inhibits H4K5 butyrylation in vitro and downregulates the expression of adipogenic genes, thereby blocking adipogenesis. LTK-14A inhibits body weight gain and reduces body weight in obese mice. LTK-14A can be used in obesity-related research.
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- CAS No.: 71118-00-8
- 화학식: C40H54O6
- 분자량:630.85
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
제품 설명
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
>20 μM
Compound: 6b
|
Antiproliferative activity against human A549 cells after 72 hrs by MTT assay
Antiproliferative activity against human A549 cells after 72 hrs by MTT assay
|
[PMID: 30500683] |
| HEL | IC50 |
>20 μM
Compound: 6b
|
Antiproliferative activity against HEL cells after 72 hrs by MTT assay
Antiproliferative activity against HEL cells after 72 hrs by MTT assay
|
[PMID: 30500683] |
| HeLa | IC50 |
19.68 μM
Compound: 6b
|
Antiproliferative activity against human HeLa cells after 72 hrs by MTT assay
Antiproliferative activity against human HeLa cells after 72 hrs by MTT assay
|
[PMID: 30500683] |
| K562 | IC50 |
>20 μM
Compound: 6b
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Antiproliferative activity against human K562 cells after 72 hrs by MTT assay
Antiproliferative activity against human K562 cells after 72 hrs by MTT assay
|
[PMID: 30500683] |
| MCF7 | IC50 |
>20 μM
Compound: 6b
|
Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay
Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay
|
[PMID: 30500683] |
In Vitro
LTK-14A (10-25 μM) selectively inhibits p300-catalyzed histone butyrylation without affecting acetyltransferase activity in in vitro reconstitution assays, and this selective inhibitory effect depends on the Cys1438 residue[1].
LTK-14A (25 μM; 6 days) is cell-permeable and exhibits metabolic stability in 3T3L1 preadipocytes[1].
LTK-14A (25 μM; 2-6 days) shows no toxicity to 3T3L1 preadipocytes[1].
LTK-14A (25 μM; 8 days) potently inhibits adipogenesis in 3T3L1 preadipocytes by suppressing the expression of pro-adipogenic genes and disrupting lipid metabolic pathways[1].
LTK-14A (25 μM) specifically inhibits histone butyrylation in 3T3L1 preadipocytes (with particularly prominent effects on H3K23 and H4K5), without altering histone acetylation or other tested post-translational modifications[1].
LTK-14A (10-1000 μg/plate) shows no mutagenicity towards Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 at high concentrations, regardless of the presence of metabolic activation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:3T3L1 pre-adipocytes
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Concentration:25 μM
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Incubation Time:2, 4 and 6 days
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Result:Does not reduce cellular oxidoreductase activity (a marker of metabolic output and viability) at any tested time point compared to control cells.
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Cell Line:3T3L1 pre-adipocytes
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Concentration:25 μM
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Incubation Time:8 days total: 2 days in differentiation medium, then 6 days in maintenance medium with alternate-day treatment
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Result:Causes a significant reduction in Oil Red-O staining, indicating strong inhibition of adipocyte differentiation.
Downregulates 2200 genes and upregulates 1309 genes compared to controls, with a predominant effect on lipid metabolism pathways.
Confirms downregulation of pro-adipogenic genes including Pparg, Lep, Slc2a4, and Adipoq via Real Time qPCR.
In Vivo
LTK-14A (50 mg/kg; p.o.; daily; for 30 consecutive days) reduces body weight, fat content, and the expression of adipogenesis-promoting genes in genetically obese db/db mice by inhibiting H4K5 butyrylation without altering histone acetylation levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 8 weeks old, high-fat diet-induced obesity model)[1]
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Dosage:50 mg/kg
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Administration:mixed with high-fat diet; 16 weeks
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Result:Produced weight gain intermediate between normal chow and untreated high-fat diet-fed mice.
Reduced epididymal fat pad weight compared to untreated high-fat diet-fed mice.
Eliminated adipocyte hypertrophy and hepatic steatosis observed in untreated high-fat diet-fed mice.
Reduced H4K5 butyrylation in liver and epididymal fat pads compared to untreated high-fat diet-fed mice.
Left histone acetylation levels (H3K14, H3K18, H4K12) unchanged across groups.
Maintained food intake similar to untreated high-fat diet-fed mice.
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Animal Model:db/db (male, 8-10 weeks old, genetic obesity model); db+/- (male, 8-10 weeks old)[1]
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Dosage:50 mg/kg
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Administration:i.g.; daily; 30 days
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Result:Arrested weight gain and reduced body weight in db/db mice by the end of the 30-day period.
Reduced liver and epididymal fat pad weights compared to vehicle-treated db/db mice.
Eliminated adipocyte hypertrophy and hepatocyte ballooning observed in vehicle-treated db/db mice.
Reduced H4K5 butyrylation in liver and epididymal fat pads compared to vehicle-treated db/db mice.
Left histone acetylation levels (H3K14, H3K18, H4K12) largely unchanged across groups.
Robustly inhibited expression of pro-adipogenic genes (Pparg, Lep, Slc2a4, Adipoq) in epididymal fat pads.
Chemical Information
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CAS No. 71118-00-8
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분자량 630.85
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화학식 C40H54O6
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SMILES
O=C([C@]1(C(C)2C)C/C=C(C)\C)[C@@](C[C@H]2C/C=C(C)/C)(C[C@@H]3C/C=C(C)\C)C(OC(C)3C)=C(C1=O)C(C(C=C4)=CC(OC)=C4OC)=O
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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.
Protocol
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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3T3-L1 preadipocyte-to-adipocyte differentiation
3T3-L1 preadipocytes are induced to differentiate after growth arrest using adipogenic media containing insulin, dexamethasone, and IBMX; differentiation is assessed by lipid-droplet accumulation, triglyceride increase, Oil Red O staining, and adipocyte-marker induction such as PPARγ and C/EBPα.
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
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Lipid Droplets: Oil Red O/Sudan Dye Lipid Staining
Lipid droplets are intracellular organelles with a neutral-lipid core that stores triacylglycerols and sterol esters, and Oil Red O or Sudan dyes detect these hydrophobic lipid deposits by partitioning into retained lipids in fresh or frozen specimens. Oil Red O stains neutral triglycerides and lipids in frozen tissue sections or air-dried cytologic preparations, while Sudan Black B has also been used as a histochemical fat stain for lipid-rich tissue structures.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)