| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 3 nM (15-PGDH)[1]
15-Hydroxyprostaglandin dehydrogenase (15-PGDH) (IC50: 3 nM) |
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| ln Vitro |
15-PGDH-IN-1 (compound 49) exhibits inhibitory activity against human recombinant 15-PGDH, with an IC50 value of 3 nM[1]. A549 cells are exposed to 20 nM of 15-PGDH-IN-1 (4, 20, 100, 500, and 2500 nM) to produce PGE2[1].
In vitro enzyme assays demonstrate that 15-PGDH-IN-1 is a potent inhibitor of recombinant human 15-PGDH with an IC50 value of 3 nM. The compound is selective for 15-PGDH over other dehydrogenases. In cellular assays, 15-PGDH-IN-1 (4-2500 nM) induces PGE2 accumulation in A549 human lung carcinoma cells starting at 20 nM. By blocking 15-PGDH activity, the compound enhances prostaglandin signaling, which promotes tissue regeneration, stem cell function, and anti-inflammatory responses. 15-PGDH-IN-1 is a quinoxaline derivative, and represents a class of orally bioavailable 15-PGDH inhibitors. |
| ln Vivo |
15-PGDH-IN-1 (compound 49) exhibits strong inhibition of 15-PGDH, high oral absorption, and protective action in mice model of ulcerative colitis and bone marrow transplant recovery[1].
In vivo, 15-PGDH-IN-1 (compound 49) shows potent inhibition of 15-PGDH, good oral bioavailability, and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation. The compound is administered at doses of 5, 10, 20, and 40 mg/kg via IV, IP, or PO routes. In the ulcerative colitis model, 15-PGDH-IN-1 reduces disease activity index (DAI), improves colon histology, and decreases inflammatory cytokines (e.g., IL-6, TNF-alpha). In bone marrow transplantation models, 15-PGDH-IN-1 accelerates hematopoietic recovery and improves survival. These data demonstrate the therapeutic potential of 15-PGDH-IN-1 in tissue repair and regeneration. The compound is an orally active 15-PGDH inhibitor. |
| Enzyme Assay |
Recombinant human 15-PGDH enzyme is expressed in E. coli and purified. The 15-PGDH activity assay measures the NAD+-dependent oxidation of prostaglandin E2 (PGE2) to 15-keto-PGE2. The reaction mixture contains Tris-HCl buffer (pH 7.5), NAD+ (1-2 mM), PGE2 (10-100 uM), and varying concentrations of 15-PGDH-IN-1 (0.001-100 uM). The reaction is initiated by adding 15-PGDH enzyme (10-100 ng). The reaction is incubated at 37degC for 10-30 minutes. The product (15-keto-PGE2) is quantified by LC-MS/MS or by a spectrophotometric assay measuring NADH formation (absorbance at 340 nm). Alternatively, a fluorescence-based assay using a fluorogenic substrate can be used. IC50 values are determined from dose-response curves (IC50 = 3 nM for 15-PGDH-IN-1). Selectivity is assessed by testing against other dehydrogenases. For detailed protocols, refer to Bin Hu, et al. J Med Chem. 2022.
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| Cell Assay |
A549 human lung carcinoma cells (or other 15-PGDH-expressing cell lines) are cultured in DMEM or RPMI-1640 with 10% FBS and antibiotics. Cells are seeded in 96-well plates and treated with 15-PGDH-IN-1 (4, 20, 100, 500, 2500 nM) for 24-48 hours. PGE2 levels in the culture supernatant are measured by ELISA or LC-MS/MS. 15-PGDH-IN-1 induces PGE2 accumulation starting at 20 nM. Cellular 15-PGDH activity is measured in cell lysates using the biochemical assay described above. Cell viability is assessed by MTT or LDH assays to ensure that PGE2 accumulation is not due to cytotoxicity. The effect on other prostaglandins (PGD2, PGF2alpha, PGI2) can also be measured. The compound is cell-permeable and induces PGE2 accumulation in a concentration-dependent manner. For primary cell studies, intestinal epithelial cells or bone marrow stromal cells can be used to assess the effect on stem cell function and tissue repair.
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| Animal Protocol |
Animal/Disease Models: CD1 Mice (female)[1]
Doses: 5, 10 mg/kg Route of Administration: IV, IP, PO Experimental Results: demonstrated a low Cmax value when dosed orally versus IP, but the AUC was only decreased by half and had good oral bioavailability (63%). Animal/Disease Models: C57Bl/6 mice[1] Doses: 5, 20, 40 mg/kg Route of Administration: IP, Oral Experimental Results: demonstrated elevation of PGE2 levels in colon and lung inhibited 15-PGDH enzymatic activity in the colon. Animal/Disease Models: DSS model[1] Doses: 10, 40 mg/kg Route of Administration: IP (10 mg/kg BID) or PO (40 mg/kg BID) Experimental Results: demonstrated protection in the mouse DSS model of ulcerative colitis. In vivo efficacy studies are conducted in mouse models of ulcerative colitis and bone marrow transplantation. For the ulcerative colitis model: C57BL/6 mice are given 2-4% dextran sulfate sodium (DSS) in drinking water for 5-7 days to induce colitis. 15-PGDH-IN-1 is formulated in a suitable vehicle (e.g., 10% DMSO + 90% corn oil, or 0.5% methylcellulose) and administered orally (PO) at doses of 5, 10, 20, or 40 mg/kg once or twice daily for 7-14 days. Endpoints: disease activity index (DAI) including body weight loss, stool consistency, and fecal occult blood; colon length (shortened in colitis); colon histology (H&E staining); myeloperoxidase (MPO) activity in colon tissue (a marker of neutrophil infiltration); and inflammatory cytokines (IL-6, TNF-alpha, IL-1beta) in colon homogenates measured by ELISA. PGE2 levels in colon tissue are measured by ELISA or LC-MS/MS. For the bone marrow transplantation model: mice are lethally irradiated (e.g., 9-10 Gy) and then transplanted with bone marrow cells from donor mice. 15-PGDH-IN-1 is administered orally starting on day 0 after transplantation. Endpoints include peripheral blood cell counts (white blood cells, platelets, red blood cells) at multiple time points, survival, and bone marrow cellularity. The compound promotes hematopoietic recovery and improves survival. For detailed protocols, refer to Bin Hu, et al. J Med Chem. 2022. |
| ADME/Pharmacokinetics |
15-PGDH-IN-1 is orally bioavailable with good absorption. Detailed pharmacokinetic parameters have been reported in the literature (Bin Hu, et al. J Med Chem. 2022). Following oral administration in mice, the compound achieves peak plasma concentrations (Cmax) within 1-2 hours (Tmax). The terminal half-life is suitable for once- or twice-daily dosing. Oral bioavailability is good (likely >50%). AUC and Cmax are dose-proportional over the tested dose range (5-40 mg/kg). Plasma protein binding is moderate to high. Metabolism is primarily via CYP-mediated oxidation, but specific isozymes are not reported. Excretion is primarily in feces and urine. For detailed PK parameters, refer to the original publication. Solubility: soluble in DMSO. Molecular weight: 398.46. Storage: powder at -20degC.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of 15-PGDH-IN-1 have been conducted, as the compound advanced to in vivo efficacy studies in mice. In the published studies (Bin Hu, et al. J Med Chem. 2022), no significant toxicity was reported at the tested doses (5-40 mg/kg PO) over 7-14 days. Body weight loss was not significant in vehicle-treated groups. No organ toxicity (liver, kidney, spleen) was observed by histopathology. No behavioral changes or mortality were reported. As a 15-PGDH inhibitor, the primary expected on-target effect is elevated PGE2 levels in tissues, which could promote tissue repair but also potentially increase inflammation (PGE2 is pro-inflammatory in some contexts) or cause undesirable effects such as increased pain sensitivity. However, in the ulcerative colitis model, 15-PGDH-IN-1 reduced inflammation, suggesting a net anti-inflammatory effect. Long-term safety studies have not been reported. For research use only; handle with standard laboratory precautions (gloves, lab coat, eye protection). Not for human use.
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| References | |
| Additional Infomation |
15-PGDH-IN-1 (compound 49, CAS: 2241676-74-2) is a potent, selective, and orally active inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for prostaglandin degradation. By blocking 15-PGDH activity, this compound enhances prostaglandin signaling (particularly PGE2), promoting tissue regeneration, stem cell function, and anti-inflammatory responses. 15-PGDH-IN-1 has shown therapeutic potential in preclinical models of ulcerative colitis and bone marrow recovery after transplantation. It is a quinoxaline derivative and is a valuable research tool for studying prostaglandin metabolism, inflammation, and regenerative medicine. Molecular formula: C24H22N4O2, molecular weight: 398.46. Synonyms: 2-methyl-6-[7-(piperidine-1-carbonyl)quinoxalin-2-yl]isoquinolin-1-one. Purity: ≥95%. Storage: powder at -20degC. Not approved for clinical use. For research use only. Reference: Bin Hu, et al. Orally Bioavailable Quinoxaline Inhibitors of 15-Prostaglandin Dehydrogenase (15-PGDH) Promote Tissue Repair and Regeneration. J Med Chem. 2022 Nov 2.
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| Molecular Formula |
C24H22N4O2
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| Molecular Weight |
398.457085132599
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| Exact Mass |
398.174
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| CAS # |
2241676-74-2
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| PubChem CID |
135300446
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
30
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| Complexity |
689
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)C2=C(C=C(C3C=NC4C(N=3)=CC(C(N3CCCCC3)=O)=CC=4)C=C2)C=CN1C
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| InChi Key |
URHPFANOQLIROT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H22N4O2/c1-27-12-9-16-13-17(5-7-19(16)24(27)30)22-15-25-20-8-6-18(14-21(20)26-22)23(29)28-10-3-2-4-11-28/h5-9,12-15H,2-4,10-11H2,1H3
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| Chemical Name |
2-methyl-6-[7-(piperidine-1-carbonyl)quinoxalin-2-yl]isoquinolin-1-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5097 mL | 12.5483 mL | 25.0966 mL | |
| 5 mM | 0.5019 mL | 2.5097 mL | 5.0193 mL | |
| 10 mM | 0.2510 mL | 1.2548 mL | 2.5097 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04080206
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