| Identification | Back Directory | [Name]
1(2H)-Isoquinolinone, 2-methyl-6-[7-(1-piperidinylcarbonyl)-2-quinoxalinyl]- | [CAS]
2241676-74-2 | [Synonyms]
1(2H)-Isoquinolinone, 2-methyl-6-[7-(1-piperidinylcarbonyl)-2-quinoxalinyl]- | [Molecular Formula]
C24H22N4O2 | [MOL File]
2241676-74-2.mol | [Molecular Weight]
398.46 |
| Chemical Properties | Back Directory | [Boiling point ]
665.1±55.0 °C(Predicted) | [density ]
1.293±0.06 g/cm3(Predicted) | [solubility ]
DMF: 30 mg/ml; DMSO: 30 mg/ml; Ethanol: 25 mg/ml | [form ]
A crystalline solid | [pka]
-0.94±0.30(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
CAY10795 is a 15-hydroxy prostaglandin dehydrogenase (15-PGDH) inhibitor (IC50 = 3 nM).1 It increases prostaglandin E2 (PGE2; ) levels greater than 3-fold in IL-1β-stimulated A549 human lung cells when used at a concentration of 500 nM. CAY10795 reduces 15-PGDH activity in the colon of mice when administered at a dose of 20 mg/kg and limits decreases in body weight and colon length and reduces colon ulceration in a mouse model of ulcerative colitis induced by dextran sodium sulfate (DSS; ) when administered at a dose of 40 mg/kg. It also accelerates recovery of circulating neutrophils following whole-body radiation and bone marrow transplant in mice when administered at a dose of 10 mg/kg twice per day. | [Uses]
15-PGDH-IN-1 is a potent and orally active 15-PGDH inhibitior. 15-PGDH-IN-1 has inhibition activity against recombinant human 15-PGDH with an IC50 value of 3 nM. 15-PGDH-IN-1 can be used for the research of tissue repair and regeneration[1]. | [in vivo]
15-PGDH-IN-1 (compound 49) (5, 10, 20, 40 mg/kg; IV, IP, PO) shows potent inhibition of 15-PGDH, good oral bioavailability, and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation[1]. | Animal Model: | CD1 Mice (female)[1] | | Dosage: | 5, 10 mg/kg | | Administration: | IV, IP, PO | | Result: | Showed a low Cmax value when dosed orally versus IP, but the AUC was only reduced by half and had good oral bioavailability (63%). |
| Animal Model: | C57Bl/6 mice[1] | | Dosage: | 5, 20, 40 mg/kg | | Administration: | IP, Oral | | Result: | Showed elevation of PGE2 levels in colon and lung inhibited 15-PGDH enzymatic activity in the colon. |
| Animal Model: | DSS model[1] | | Dosage: | 10, 40 mg/kg | | Administration: | IP (10 mg/kg BID) or PO (40 mg/kg BID) | | Result: | Showed protection in the mouse DSS model of ulcerative colitis. |
| [References]
1. Hu, B., Toda, K., Wang, X., et al. Orally bioavailable quinoxaline inhibitors of 15-prostaglandin dehydrogenase (15-PGDH) promote tissue repair and regeneration J. Med. Chem. 65(22),15327-15343(2022). |
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