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| Other Sizes |
| Targets |
KAT8-IN-1 targets lysine acetyltransferase 8 (KAT8), also known as MOF (males absent on the first), which is a histone acetyltransferase (HAT). KAT8 acetylates histone H4 at lysine 16 (H4K16ac), a mark associated with transcriptional activation. Dysregulation of KAT8 and other HATs can contribute to diseases such as cancer and inflammatory diseases. KAT8-IN-1 inhibits histone acetyltransferases with IC50 values of 141 μM for KAT8, 221 μM for KAT2B, and 106 μM for KAT3B. The compound's mechanism involves competitive inhibition of the acetyltransferase activity. A distinctive feature of this compound is the detailed characterization of its inhibitory mechanism, including the calculation of both free enzyme and acetylated intermediate binding constants (Ki). The compound is used as a fragment for medicinal chemistry and drug discovery.
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| ln Vitro |
KAT8-IN-1 (compound 19) no longer exhibits antioxidant action (EC50>1 mM)[1].
In vitro, KAT8-IN-1 inhibits lysine acetyltransferase 8 (KAT8) activity with an IC50 of 141 μM. The compound also inhibits KAT2B with an IC50 of 221 μM and KAT3B with an IC50 of 106 μM. The compound's inhibitory activity has been characterized in detail, including the calculation of Ki values: 23 μM for free KAT8 and 190 μM for acetylated KAT8, representing an 8.3-fold shift that enables mechanistic autoacetylation studies. KAT8-IN-1 is a fragment molecule that can be used as a building block for medicinal chemistry and drug discovery. The compound's fragment properties minimize aggregation and non-specific binding in biophysical assays. Broad-spectrum HAT inhibitors suffer from off-target effects, while KAT8-IN-1 addresses this gap with a rigorously defined, fragment-based kinetic profile. |
| ln Vivo |
KAT8-IN-1 is not used as a therapeutic agent but rather as a research tool for studying histone acetyltransferase function and for fragment-based drug discovery. The compound is used in epigenetic research to study the role of KAT8 and other HATs in gene regulation and disease. KAT8-IN-1 is a fragment molecule that can serve as a starting point for the development of more potent KAT8 inhibitors. It is used in medicinal chemistry for fragment-based drug design and optimization. The compound's role as a chemical probe allows researchers to investigate the biological functions of KAT8 and the therapeutic potential of targeting this enzyme in cancer and inflammatory diseases. The compound is not approved for clinical use.
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| Enzyme Assay |
In vitro enzyme assays for KAT8-IN-1 typically involve measuring the inhibition of histone acetyltransferase (HAT) activity. The compound is dissolved in DMSO to prepare stock solutions and diluted in assay buffer to concentrations ranging from 1-1000 μM. For HAT assays, recombinant KAT8, KAT2B, or KAT3B enzymes are incubated with histone substrates, acetyl-CoA, and varying concentrations of the compound. The incorporation of [3H]-acetyl or detection of acetylated histone using antibodies is measured. IC50 values are calculated by plotting the percentage of inhibition against the compound concentration. For Ki determination, enzyme kinetics are measured at various substrate and inhibitor concentrations. The compound is soluble in DMSO at 100 mg/mL (528.63 mM).
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| Cell Assay |
In vitro cell-based assays using KAT8-IN-1 are conducted in cell culture models to study the effects of KAT8 inhibition on histone acetylation and gene expression. Cells are treated with the compound at concentrations ranging from 10-500 μM for 24-72 hours. Histone acetylation levels are measured by Western blot using antibodies specific for acetylated histone H4K16. Gene expression changes are analyzed by qPCR or RNA sequencing. Cell viability is assessed using MTT or CCK-8 assays. The compound is typically dissolved in DMSO and diluted in cell culture medium, with the final DMSO concentration kept below 0.1%. The compound's effects on histone acetylation and gene expression are concentration-dependent. The compound is stored at 4°C under nitrogen.
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| Animal Protocol |
In vivo animal experiments with KAT8-IN-1 are not well-documented as the compound is primarily used as a research tool and fragment for drug discovery. The compound's moderate potency (IC50 141 μM) suggests that high doses would be required for in vivo studies, which may limit its use in animal models. However, as a fragment molecule, KAT8-IN-1 may be used as a starting point for the development of more potent KAT8 inhibitors with improved pharmacokinetic properties for in vivo use. The compound is intended for research use only and is not approved for clinical applications. If used in animal studies, the compound would likely be formulated in appropriate vehicles such as DMSO, PEG, or saline for administration.
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| ADME/Pharmacokinetics |
KAT8-IN-1 has a molecular weight of 189.17 g/mol and the formula C10H7NO3. The compound is soluble in DMSO at 100 mg/mL (528.63 mM). For long-term storage, the compound is stored at 4°C under nitrogen. The compound's pharmacokinetic properties have not been extensively characterized as it is primarily used as a research tool. The compound is a fragment molecule that can serve as a building block for medicinal chemistry and drug discovery. Its moderate potency and well-characterized kinetic profile make it useful for fragment-based drug design. The compound's parent scaffold is 4-amino-1-naphthol, and it is also known as 4-nitro-1-naphthol. The compound is stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
The toxicity of KAT8-IN-1 has not been extensively characterized as the compound is primarily used as a research tool for in vitro studies. The compound is intended for research use only and is not for human use. Standard laboratory safety precautions should be followed when handling the compound, including the use of gloves and eye protection. The compound is a small-molecule inhibitor of histone acetyltransferases, and its toxicity in cell culture is likely concentration-dependent. At higher concentrations, the compound may affect cell viability due to inhibition of essential epigenetic processes. The compound is not classified as a highly toxic substance but should be handled with appropriate care. Safety data sheets recommend standard handling procedures for research chemicals.
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| References |
[1]. Wapenaar H, et al. The relevance of Ki calculation for bi-substrate enzymes illustrated by kinetic evaluation of a novel lysine (K) acetyltransferase 8 inhibitor. Eur J Med Chem. 2017 Aug 18;136:480-486.
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| Additional Infomation |
KAT8-IN-1 (CAS 605-62-9) is a small-molecule fragment inhibitor targeting lysine acetyltransferase 8 (KAT8, also known as MOF). The compound has the molecular formula C10H7NO3 and a molecular weight of 189.17 g/mol. It is also known as 4-nitro-1-naphthol. KAT8-IN-1 was identified through a fragment screening approach, with its parent scaffold being 4-amino-1-naphthol. The compound exhibits moderate inhibitory potency with IC50 values of 141 μM for KAT8, 221 μM for KAT2B, and 106 μM for KAT3B. A distinctive feature is the detailed characterization of its inhibitory mechanism, including Ki values of 23 μM for free KAT8 and 190 μM for acetylated KAT8. KAT8-IN-1 is used as a fragment molecule for medicinal chemistry and drug discovery research. It is soluble in DMSO at 100 mg/mL and stored at 4°C under nitrogen. The compound is intended for research use only.
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| Molecular Formula |
C10H7NO3
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| Molecular Weight |
189.1675
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| Exact Mass |
189.042
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| CAS # |
605-62-9
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| PubChem CID |
343829
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| Appearance |
Yellow to brown solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
398.8±25.0 °C at 760 mmHg
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| Melting Point |
165-168°C
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| Flash Point |
179.8±11.6 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.714
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
14
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| Complexity |
226
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C1=C([H])C([H])=C(C2=C([H])C([H])=C([H])C([H])=C21)[N+](=O)[O-]
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~528.63 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (5.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.2863 mL | 26.4313 mL | 52.8625 mL | |
| 5 mM | 1.0573 mL | 5.2863 mL | 10.5725 mL | |
| 10 mM | 0.5286 mL | 2.6431 mL | 5.2863 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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