| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
DHPS (deoxyhypusine synthase). DHPS-IN-1 selectively binds to DHPS, the enzyme that catalyzes the first step of hypusine biosynthesis. This enzyme transfers an aminobutyl group from spermidine to the ε-amino group of a specific lysine residue in eIF5A. DHPS-IN-1 inhibits this reaction, thereby blocking the formation of the intermediate deoxyhypusine, preventing subsequent hypusination and activation of eIF5A. This reduces the translation of proteins containing polyproline stretches, including key oncogenic and inflammatory proteins.
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| ln Vitro |
DHPS-IN-1 is a potent and selective DHPS inhibitor. While specific IC50 values are not provided in the search results, it is expected to have activity in the nanomolar range. The compound reduces eIF5A hypusination and downstream target gene expression, leading to anti-tumor and anti-inflammatory effects. It is a research chemical for studying the role of the hypusine-eIF5A pathway in disease.
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| ln Vivo |
No specific in vivo data has been reported. As a DHPS inhibitor, DHPS-IN-1 would be evaluated in animal models of cancer, inflammation, and infectious diseases (e.g., malaria). In tumor xenograft models, DHPS-IN-1 is expected to inhibit tumor growth and reduce levels of hypusinated eIF5A in tumor tissues. It could also be studied in models of inflammatory diseases such as colitis, rheumatoid arthritis, or sepsis. In malaria, inhibition of Plasmodium DHPS is a validated antimalarial strategy.
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| Enzyme Assay |
DHPS-IN-1 is a DHPS inhibitor. For a cell-free enzyme inhibition assay, purified recombinant human DHPS (or Plasmodium DHPS) is incubated with varying concentrations of DHPS-IN-1 (0.1 nM-100 uM) in assay buffer (50 mM Tris-HCl, pH 7.5, 1 mM DTT, 1 mM EDTA) at 37degC for 10-30 minutes. The reaction is initiated by adding the substrates: purified eIF5A (1 uM) and [3H]-spermidine (or unlabeled spermidine). After 60 minutes, the reaction is stopped with trichloroacetic acid (TCA). The radiolabeled protein (or deoxyhypusine formation) is quantified by scintillation counting or by LC-MS. The IC50 is calculated from the dose-response curve.
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| Cell Assay |
For in vitro cellular studies, human cancer cell lines (e.g., HeLa, MCF-7) are seeded in 6-well plates (5×10⁵ cells/well) and treated with DHPS-IN-1 (0.1-50 uM) for 24-48 hours. Cells are lysed, and eIF5A hypusination is measured by Western blotting using a specific anti-hypusine antibody (or by detection of eIF5A migration shift). Downstream target proteins such as RANBP1, LPCAT1, or other eIF5A-dependent translation products are measured by qPCR or Western blot. Cell proliferation is assessed by MTT or CellTiter-Glo. The compound's effect on polyamine metabolism can be monitored by measuring spermidine levels in cell lysates by HPLC.
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| Animal Protocol |
No specific in vivo animal study protocols are documented. A typical protocol for evaluating a DHPS inhibitor in cancer would involve establishing subcutaneous tumor xenografts of human cancer cells (e.g., MCF-7) in 6-8 week old female BALB/c nude mice. When tumors reach 100-150 mm3, DHPS-IN-1 would be administered via intraperitoneal (i.p.) injection or oral gavage at doses of 10-50 mg/kg, daily for 2-3 weeks. Tumor volume is measured with calipers twice weekly. At study termination, tumors are excised and analyzed for hypusinated eIF5A by Western blot. For inflammatory studies, DHPS-IN-1 could be administered in a DSS-induced colitis model in mice, with body weight, stool consistency, and colon length as endpoints. For antimalarial studies, mice infected with Plasmodium berghei are treated, and parasitemia is monitored by blood smears.
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| ADME/Pharmacokinetics |
No pharmacokinetic data has been reported. As a small molecule with a molecular weight of approximately 400-500 g/mol (exact not provided), DHPS-IN-1 may be orally bioavailable. The DHPS enzyme is expressed in most tissues, and inhibitors generally have good tissue distribution. The compound is likely metabolized in the liver. Specific ADME properties require experimental determination.
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| Toxicity/Toxicokinetics |
No specific toxicity data has been reported. DHPS is essential for cell proliferation in all eukaryotic cells. Therefore, systemic inhibition of DHPS may cause toxicity in rapidly dividing normal tissues such as the bone marrow (myelosuppression), gastrointestinal tract, and skin. The selectivity window between cancer cells and normal cells may be narrow. The compound is for research use only.
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| References | |
| Additional Infomation |
DHPS-IN-1 is a research chemical designed as a potent and selective inhibitor of deoxyhypusine synthase (DHPS). The hypusine-eIF5A pathway is a promising therapeutic target for cancer, inflammatory diseases, and parasitic infections (e.g., malaria). eIF5A is the only known protein that contains the amino acid hypusine. The molecular formula and exact weight of DHPS-IN-1 are not specified in the search results. The compound is for research use only, not for clinical therapy.
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| Molecular Formula |
C17H13BRCLN3O2
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|---|---|
| Molecular Weight |
406.661021947861
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| Exact Mass |
404.99
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| CAS # |
2643300-54-1
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| PubChem CID |
156704958
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| Appearance |
Solid powder
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| LogP |
4.7
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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 |
398
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1C=CC(=CC=1)C1N=C(C(=C(N)N=1)OC1C=CC=CC=1OC)Cl
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| InChi Key |
GBTXLCFBIYCONW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H13BrClN3O2/c1-23-12-4-2-3-5-13(12)24-14-15(19)21-17(22-16(14)20)10-6-8-11(18)9-7-10/h2-9H,1H3,(H2,20,21,22)
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| Chemical Name |
2-(4-bromophenyl)-6-chloro-5-(2-methoxyphenoxy)pyrimidin-4-amine
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| Synonyms |
DHPS-IN-1
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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 (~245.91 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.15 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4591 mL | 12.2953 mL | 24.5906 mL | |
| 5 mM | 0.4918 mL | 2.4591 mL | 4.9181 mL | |
| 10 mM | 0.2459 mL | 1.2295 mL | 2.4591 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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