| CAS NO: | 1033836-12-2 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| Molecular Weight (MW) | 381.37 |
|---|---|
| Formula | C19H19F4N3O |
| CAS No. | 1033836-12-2 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 10 mM |
| Water: <1 mg/mL | |
| Ethanol: | |
| SMILES Code | O=C(C1=CC=C(C2=CC=CC(F)=C2)N=C1)NC3CCN(CC(F)(F)F)CC3 |
| Synonyms | HPGDS Inhibitor I; H-PGDS Inhibitor I; Prostaglandin D Synthase (hematopoietic-type) Inhibitor I. |
| In Vitro | In vitro activity: HPGDS Inhibitor I (also known as H-PGDS inhibitor 1) is a novel, orally bioavailable, potent and selective inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS) with IC50 Value of 0.7 nM. The compound illustrated equal potency against purified HPGDS from human , rat, dog, and sheep with IC50 in the range of 0.5-2.3 nM. Hematopoietic prostaglandin D synthase (HPGDS) is primarly expressed in mast cells, antigen-presenting cells, and Th-2 cells. HPGDS converts PGH2 into PGD2, a mediator thought to play a pivotal role in airway allergy and inflammatory processes. HPGDS Inhibitor I reduces the antigen-induced response in allergic sheep. Kinase Assay: HPGDS Inhibitor I (also known as H-PGDS inhibitor 1) is a novel, orally bioavailable, potent and selective inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS) with IC50 Value of 0.7 nM. The compound illustrated equal potency against purified HPGDS from human , rat, dog, and sheep with IC50 in the range of 0.5-2.3 nM. Cell Assay: HPGDS inhibitor 1 was profiled in a panel of cellular assays to screen for activity against several relevant human enzyme targets. Those assay indicated that HPGDS inhibitor 1 does not inhibit human L- PGDS, m-PGDS, COX-1, COX-2 or 5 LOX (IC50 values> 10000 nM). HPGDS inhibitor 1 had a solubility of 1.5 ug/ml (3.9 uM) at pH 6.5. |
|---|---|
| In Vivo | HPGDS Inhibitor I reduces the antigen-induced response in allergic sheep. The sheep used in these experiments develop AHR 24 h post Ascaris challenge. Vehicle did not inhibit allergen-induced AHR (significant fall in postantigen PC 400), whereas administration of 8 completely protected against allergen-induced AHR to carbachol provocation; the PC400% pre- and postchallenges were not significantly different (p = 0.89).Also the compound had excellent PK characteristics when dosed in rats at 1 mpk with 76% bioavailavility. Rats dosed orally with 1 and 10 mpk HPGDS inhibitor 1 were sacrificed at various times, and plasma concentrations of HPGDS inhibitor 1 and spleen PGD2 concentrations were measured. Oral administration of HPGDS inhibitor 1 blocked PGD2 production in the rat spleen; inhibition of PGD2 was inversely correlated with the plasma concentration of HPGDS inhibitor 1 in a time and dose-dependent manner. Spleen PGD2 levels fall as HPGDS inhibitor 1 plasma levels increase over time; PGD2 levels return to baseline levels as HPGDS inhibitor 1 plasma levels decline. |
| Animal model | Rats and sheep |
| Formulation & Dosage | 1 and 10 mpk |
| References | ACS Med Chem Lett. 2010 Feb 2;1(2):59-63. |
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