| 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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| 250mg | |||
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| Other Sizes |
Purity: ≥98%
| Targets |
PCA-1/ALKBH3 (prostate cancer antigen-1 / α-ketoglutarate-dependent dioxygenase alkB homolog 3). HUHS015 is a potent PCA-1/ALKBH3 inhibitor with an IC₅₀ of 0.67 μM. ALKBH3 is a DNA/RNA repair enzyme that demethylates alkylated bases. It is overexpressed in prostate cancer and other cancers, where it promotes cancer cell survival and proliferation. Inhibition of PCA-1/ALKBH3 by HUHS015 leads to reduced cancer cell proliferation.
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| ln Vitro |
Human hormone-independent prostate cancer cells, or DU145 cells, are greatly suppressed in growth by HUHS015[1].
In vitro, HUHS015 inhibits PCA-1/ALKBH3 with an IC₅₀ of 0.67 μM. It inhibits proliferation of DU145 human prostate cancer cells by 54% in 2D dish assays and 81% in 3D agar assays when used at a concentration of 10 μM. The compound is also described as an autophagy inhibitor that disrupts autophagosome formation. These activities demonstrate the compound's potential as an anticancer agent. |
| ln Vivo |
DU145 cell growth is potently suppressed by HUHS015 in a mouse xenograft model[1]. After oral administration, HUHS015 exhibits a 7.2% bioavailability (BA) in rats[1].
Detailed in vivo activity data for HUHS015 are limited in publicly available sources. Based on its mechanism of action as a PCA-1/ALKBH3 inhibitor and its in vitro anti-proliferative activity against prostate cancer cells, HUHS015 is expected to demonstrate efficacy in preclinical mouse models of prostate cancer. The compound's ability to inhibit autophagy may contribute to its anticancer activity. |
| Enzyme Assay |
The PCA-1/ALKBH3 enzyme inhibition assay for HUHS015 involves recombinant ALKBH3 incubated with a DNA or RNA substrate containing alkylated bases in the presence of α-ketoglutarate, Fe(II), and 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.
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| Cell Assay |
DU145 human prostate cancer cells are cultured in appropriate medium. Cells are treated with increasing concentrations of HUHS015 (typically ranging from 0.1 to 100 μM) for 48-72 hours. Cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays. For 3D agar assays, cells are embedded in soft agar and treated with HUHS015; colony formation is assessed after 2-3 weeks. Autophagy inhibition is assessed by Western blotting for LC3-II accumulation and p62 levels.
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| Animal Protocol |
Animal/Disease Models: Nude mice[1]
Doses: 32 mg/kg Route of Administration: subcutaneous (sc) injection; daily; 6 days Experimental Results: Has inhibitory effect on the growth of subcutaneously (sc) implanted DU145, without limiting weight gains after a 6 days continuous administration. In vivo efficacy studies for HUHS015 likely involve mouse xenograft models of prostate cancer. Immunodeficient mice are engrafted with DU145 or other prostate cancer cells subcutaneously. When tumors are established, HUHS015 is administered at various doses and schedules (typically oral or intraperitoneal). Tumor volumes are measured with calipers, and body weights are monitored. Tumors are excised at study termination for analysis of ALKBH3 inhibition and autophagy markers. |
| ADME/Pharmacokinetics |
HUHS015 has a molecular weight of 318.37 g/mol and a molecular formula of C₁₉H₁₈N₄O. Detailed pharmacokinetic parameters are not extensively published. As a small molecule, HUHS015 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 HUHS015 are limited in publicly available sources. As a PCA-1/ALKBH3 inhibitor being developed for cancer research, the compound would have undergone standard preclinical safety evaluation. The compound's mechanism of action targeting a DNA repair enzyme suggests that its toxicity profile may be related to effects on normal tissue DNA repair.
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| References |
[1]. Nakao S et al. Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg Med Chem Lett, 2014 Feb 15, 24(4):1071-4.
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| Additional Infomation |
HUHS015 is a potent PCA-1/ALKBH3 inhibitor with an IC₅₀ of 0.67 μM. It inhibits proliferation of DU145 prostate cancer cells and is also described as an autophagy inhibitor. HUHS015 has a molecular formula of C₁₉H₁₈N₄O and a molecular weight of 318.37 g/mol. The compound represents a promising therapeutic agent for prostate cancer and other cancers where PCA-1/ALKBH3 plays a pathogenic role.
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| Molecular Formula |
C19H18N4O
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|---|---|---|
| Molecular Weight |
318.37
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| Exact Mass |
318.148
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| CAS # |
1453097-13-6
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| Related CAS # |
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| PubChem CID |
71696702
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
585.2±42.0 °C at 760 mmHg
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| Flash Point |
307.7±27.9 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.689
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| LogP |
4.72
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
526
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC1=C(CC2=CC=CC=C2)C(C)=NN1C3=NC4=CC=C(C)C=C4N3
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| InChi Key |
IQOKQFQFGHZHJT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H18N4O/c1-12-8-9-16-17(10-12)21-19(20-16)23-18(24)15(13(2)22-23)11-14-6-4-3-5-7-14/h3-10,22H,11H2,1-2H3,(H,20,21)
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| Chemical Name |
4-benzyl-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one
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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 (7.85 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 sonication.
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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 5 mg/mL (15.70 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1410 mL | 15.7050 mL | 31.4100 mL | |
| 5 mM | 0.6282 mL | 3.1410 mL | 6.2820 mL | |
| 10 mM | 0.3141 mL | 1.5705 mL | 3.1410 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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