| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
KDM5B (JARID1B or PLU1), a histone demethylase. GSK467 is a cell penetrant and selective inhibitor of KDM5B.
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| ln Vitro |
GSK467 (0-100 μM; 6 days) exhibits antiproliferative effects on human multiple myeloma tumor cells [1]. The 2-OG binding pocket is located by GSK467 [2]. GSK467 prevents the spheroid and colony formation of HCC cells.
GSK467 inhibits KDM5B with a Ki of 10 nM and an IC50 of 26 nM. It shows apparent 180-fold selectivity for KDM4C and no measurable inhibitory effects toward KDM6 or other Jumonji family members. GSK467 demonstrates antiproliferative effects on human multiple myeloma and HCC cells. GSK467 (0-100 μM; 6 days) exhibits antiproliferative effects on human multiple myeloma tumor cells. GSK467 is located in the 2-OG-binding pocket. |
| ln Vivo |
In female BALB/c nude mice, GSK-467 can suppress the development and proliferation of HCC tumor cells by upregulating the expression of miR-448 and blocking YTHDF3/ITGA6 blue [3].
In vivo, GSK467 suppresses HCC tumor growth by upregulating miR-448 and downregulating the YTHDF3/ITGA6 pathway. In female BALB/c nude mice, GSK-467 can suppress the development and proliferation of HCC tumor cells. Specific dosing regimens are available in the primary literature. The compound's ability to modulate histone methylation and gene expression makes it a valuable tool for studying epigenetic regulation in cancer. |
| Enzyme Assay |
KDM5B inhibition is assessed using in vitro enzyme assays with recombinant KDM5B and a histone substrate (e.g., H3K4me3 peptide). Demethylation activity is measured by detecting the conversion of methylated to demethylated products using mass spectrometry, antibody-based detection (e.g., anti-H3K4me3 antibodies in ELISA or AlphaScreen formats), or by measuring formaldehyde release. Ki and IC50 values are calculated from dose-response curves using nonlinear regression analysis. Selectivity is evaluated by profiling against other Jumonji family members including KDM4C, KDM6, and other KDM5 family members.
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| Cell Assay |
cell proliferation assay [1]
Cell Types: Human multiple myeloma tumor cell line MM.1S Tested Concentrations: 0-100 μM Incubation Duration: 6 days Experimental Results: Demonstrated anti-proliferation Effect, IC50>50 μM. Cellular activity is evaluated in multiple myeloma and HCC cell lines. Cells are treated with GSK467 at various concentrations (typically 0.1-100 μM) for appropriate time periods (e.g., 6 days for proliferation assays, 24-72 hours for gene expression). Cell proliferation is assessed by MTT, CellTiter-Glo, or colony formation assays. Histone methylation levels (H3K4me3, H3K4me2, H3K4me1) are assessed by Western blot using specific antibodies. miR-448 expression is measured by qRT-PCR. YTHDF3 and ITGA6 expression is measured by qRT-PCR or Western blot. Apoptosis is assessed by caspase-3/7 activation or Annexin V staining. Cell cycle distribution is analyzed by flow cytometry. |
| Animal Protocol |
In vivo efficacy is studied in female BALB/c nude mouse xenograft models of HCC. GSK467 is administered via various routes (oral, intraperitoneal) at doses determined from pharmacokinetic and tolerability studies. Tumor growth is measured by caliper twice weekly and tumor volume is calculated. At study termination, tumors are excised and weighed. Tumor tissues are analyzed for miR-448 expression (qRT-PCR), YTHDF3 and ITGA6 expression (qRT-PCR, Western blot, immunohistochemistry), histone methylation levels (Western blot, immunohistochemistry), and proliferation markers (Ki-67 immunohistochemistry). Pharmacodynamic markers include H3K4me3 levels, miR-448 expression, and YTHDF3/ITGA6 pathway activity in tumor tissue.
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| ADME/Pharmacokinetics |
GSK467 has a molecular formula of C19H18N4O and a molecular weight of 318.37 g/mol. CAS Number: 1628332-52-4. It is a cell penetrant and selective KDM5B inhibitor. Purity: typically ≥98% by HPLC. The compound is soluble in DMSO, water, and ethanol. Storage: store at -20°C for long-term stability, protected from light and moisture. Detailed pharmacokinetic parameters including half-life, oral bioavailability, volume of distribution, and plasma protein binding are available from the primary literature.
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| Toxicity/Toxicokinetics |
Safety data for GSK467 indicate it is a research compound for laboratory use only. As a histone demethylase inhibitor, it may have epigenetic effects on gene expression, cell proliferation, and differentiation. Specific toxicological profiles including acute toxicity, organ toxicity, genotoxicity, and reproductive toxicity are not extensively published. Standard laboratory safety practices should be followed during handling, including the use of personal protective equipment and adequate ventilation. The compound is for research use only and not for human therapeutic applications without appropriate regulatory approval. Consult the material safety data sheet (MSDS) for detailed safety information.
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| References |
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| Additional Infomation |
GSK467 is a research tool compound for studying KDM5B biology and epigenetic regulation. It is not approved for clinical use. The compound has been investigated for its antiproliferative effects on multiple myeloma and HCC, and for its ability to suppress HCC tumor growth by modulating miR-448 and the YTHDF3/ITGA6 pathway. GSK467 is a cell penetrant and selective inhibitor of KDM5B (JARID1B/PLU1) with a Ki of 10 nM. It shows apparent 180-fold selectivity for KDM4C and no measurable inhibitory effects toward KDM6 or other Jumonji family members. GSK467 is located in the 2-OG-binding pocket. The compound prevents the removal of methyl groups from histones, influencing gene expression by maintaining histone methylation. GSK467 is used to study epigenetic regulation in various diseases.
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| Molecular Formula |
C17H13N5O2
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| Molecular Weight |
319.317422628403
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| Exact Mass |
319.106
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| CAS # |
1628332-52-4
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| PubChem CID |
135567128
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| Appearance |
White to off-white solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
491
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1=NC2C=NC=CC=2C(N1)=O)C1C=NN(C=1)CC1C=CC=CC=1
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| InChi Key |
ZTYRLXUTLYBVHH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H13N5O2/c23-16-14-6-7-18-9-15(14)20-17(21-16)24-13-8-19-22(11-13)10-12-4-2-1-3-5-12/h1-9,11H,10H2,(H,20,21,23)
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| Chemical Name |
2-(1-benzylpyrazol-4-yl)oxy-3H-pyrido[3,4-d]pyrimidin-4-one
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| Synonyms |
GSK 467; GSK-467; GSK467
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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 |
| 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 : ~20.83 mg/mL (~65.23 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (6.51 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. Solubility in Formulation 2: 2.08 mg/mL (6.51 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 3.1317 mL | 15.6583 mL | 31.3165 mL | |
| 5 mM | 0.6263 mL | 3.1317 mL | 6.2633 mL | |
| 10 mM | 0.3132 mL | 1.5658 mL | 3.1317 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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