| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
KDM5B (lysine‑specific demethylase 5B) – no IC50/Ki/EC50 values provided; AS8351 is proposed to inhibit KDM5B by competing with α‑ketoglutarate for iron chelation, based on functional knockdown studies. [2]
KDM5B (JARID1B, histone H3K4 demethylase). AS8351 is an iron chelator that inhibits histone demethylase KDM5B by competing with α-ketoglutarate. KDM5B is a histone H3K4 demethylase involved in regulation of cell proliferation and stem cell self-renewal and differentiation. Inhibition of KDM5B by AS8351 affects epigenetic modifications and gene expression. |
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| ln Vitro |
By competing with α-ketoglutarate (α-KG) to chelate iron [Fe(II)] in specific epigenetic enzymes, like the JmjC-containing structure that needs α-KG and iron domain-based histone demethylase (JmjC-KDM) as a cofactor, AS8351 influences epigenetic modifications [2].
AS8351 was included in a 9‑compound cocktail (9C: CHIR99021, A‑83‑01, BIX01294, AS8351, SC1, Y27632, OAC2, SU16F, JNJ10198409) that converted human foreskin fibroblasts (HFFs) and human fetal lung fibroblasts (HLFs) into chemically induced cardiomyocyte‑like cells (ciCMs). Removal of AS8351 from 9C significantly reduced the number of beating clusters and the percentage of cTNT⁺ cells, indicating it is indispensable for cardiac reprogramming (Fig. 1E, fig. S2B). [2] Knockdown of KDM5B by shRNA or use of the KDM5B inhibitor PBIT phenocopied the effect of AS8351 in generating ciCMs, suggesting that KDM5B is a functional target of AS8351. AS8351 is hypothesized to affect epigenetic modifications by competing with α‑ketoglutarate for chelating iron/Fe(II) in JmjC‑domain‑containing histone demethylases. [2] In vitro, AS8351 inhibits histone demethylase KDM5B. It has been used in combination with other compounds to induce reprogramming of human fetal lung fibroblasts into functional cardiomyocytes. AS8351 inhibits breast cancer cell proliferation and migration. The compound's epigenetic effects make it a valuable tool for studying cell fate determination and cancer biology. |
| ln Vivo |
Detailed in vivo activity data for AS8351 are limited in publicly available sources. Based on its mechanism of action as a KDM5B inhibitor and its in vitro activities, AS8351 is expected to demonstrate efficacy in preclinical models of cancer and possibly cardiac regeneration. The compound's ability to induce cardiac reprogramming suggests potential for regenerative medicine applications.
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| Enzyme Assay |
The KDM5B enzyme inhibition assay for AS8351 involves recombinant KDM5B incubated with a histone H3 peptide substrate and α-ketoglutarate (α-KG) in the presence of varying concentrations of the compound. Demethylase activity is measured by quantifying the removal of methyl groups from the substrate using methods such as mass spectrometry, radioactive labeling, or fluorescent assays. IC₅₀ values are calculated from dose-response curves. AS8351 inhibits KDM5B by competing with α-KG for iron chelation.
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| Cell Assay |
Cell reprogramming assay: Human foreskin fibroblasts (HFFs) were treated with a cocktail of 9 compounds including AS8351 at a concentration of 5 μM (table S2) for 6 days in DMEM/F12 medium supplemented with 10% FBS and 1% nonessential amino acids. Then cells were cultured in cardiac induction medium (CIM) containing activin A, BMP4, VEGF, and CHIR99021 for 5 days, followed by replating in human CM‑conditioned medium. At day 30, cells were analyzed for beating clusters, cTNT expression by flow cytometry, and cardiomyocyte markers by immunofluorescence. [2]
Human fetal lung fibroblasts or breast cancer cell lines are cultured in appropriate medium. For cardiac reprogramming studies, fibroblasts are treated with AS8351 in combination with other small molecules (e.g., CHIR99021, A 83-01, BIX01294, SC-1, Y-27632, OAC2, SU 16f, and JNJ-10198409). Cardiac reprogramming is assessed by staining for cardiac markers (e.g., cTnT, α-actinin) and by functional assays (e.g., spontaneous contraction). For cancer studies, cell proliferation and migration are assessed. |
| Animal Protocol |
In vivo efficacy studies for AS8351 likely involve mouse models of cancer or cardiac injury. For cancer models, immunodeficient mice are engrafted with human tumor cells subcutaneously. When tumors are established, AS8351 is administered at various doses and schedules. Tumor volumes are measured, and tumors are excised for analysis of KDM5B inhibition and other biomarkers. For cardiac regeneration studies, mouse models of myocardial infarction may be used.
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| ADME/Pharmacokinetics |
AS8351 has a molecular weight of 291.30 g/mol and a molecular formula of C₁₇H₁₃N₃O₂. Detailed pharmacokinetic parameters are not extensively published. As a small molecule, AS8351 is expected to be orally bioavailable. The compound is typically stored as a powder at -20°C. Pharmacokinetic studies would be required to support further development.
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| Toxicity/Toxicokinetics |
Detailed toxicology data for AS8351 are limited in publicly available sources. As an iron chelator and KDM5B inhibitor, the compound's mechanism of action may affect normal cellular processes. Standard preclinical safety evaluation would be required for further development. The compound has been used in cell reprogramming studies and cancer research.
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| References | |
| Additional Infomation |
AS8351 was identified as an indispensable component of a 9‑compound chemical cocktail (9C) that reprograms human fibroblasts into functional cardiomyocytes (ciCMs). It is a KDM5B inhibitor, and its removal significantly reduces reprogramming efficiency. The compound is thought to modulate chromatin structure by promoting active histone methylation marks (H3K4me3, H3K27ac) at heart developmental gene loci. [2]
AS8351 is an iron chelator that inhibits histone demethylase KDM5B by competing with α-ketoglutarate. It is one of nine compounds that efficiently induce cardiac reprogramming of fibroblasts into functional cardiomyocytes. AS8351 also inhibits breast cancer cell proliferation and migration. The compound has a molecular formula of C₁₇H₁₃N₃O₂ and is used in epigenetic and regenerative medicine research. |
| Molecular Formula |
C17H13N3O2
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|---|---|---|
| Molecular Weight |
291.3
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| Exact Mass |
291.101
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| Elemental Analysis |
C, 70.09; H, 4.50; N, 14.42; O, 10.98
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| CAS # |
796-42-9
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| Related CAS # |
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| PubChem CID |
135400486
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.364g/cm3
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| Boiling Point |
503.5ºC at 760 mmHg
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| Melting Point |
266 °C
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| Flash Point |
258.3ºC
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| Index of Refraction |
1.715
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| LogP |
3.095
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
407
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=CN=CC=1)NN=CC1C2C(=CC=CC=2)C=CC=1O
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| InChi Key |
WQSHHAVECQJKLX-YBFXNURJSA-N
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| InChi Code |
InChI=1S/C17H13N3O2/c21-16-6-5-12-3-1-2-4-14(12)15(16)11-19-20-17(22)13-7-9-18-10-8-13/h1-11,21H,(H,20,22)/b19-11+
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| Chemical Name |
N-[(E)-(2-hydroxynaphthalen-1-yl)methylideneamino]pyridine-4-carboxamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.58 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL 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 | 3.4329 mL | 17.1644 mL | 34.3289 mL | |
| 5 mM | 0.6866 mL | 3.4329 mL | 6.8658 mL | |
| 10 mM | 0.3433 mL | 1.7164 mL | 3.4329 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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