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Formula | C12H9FN2O2 |
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Molecular Weight | 232.21 | CAS No. | 198474-05-4 | ||||||||
Solubility (25°C)* | In vitro | DMSO | 46 mg/mL (198.09 mM) | ||||||||
Ethanol | 6 mg/mL (25.83 mM) | ||||||||||
Water | Insoluble | ||||||||||
In vivo (Add solvents to the product individually and in order) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | PF-06840003 (EOS200271) is a highly selective orally bioavailable IDO-1 inhibitor. Although it has moderate hIDO1 enzyme inhibition (IC50 0.41 μM), it is a highly efficient compound (LE 0.53, LipE 5.1), driven by its tight packing within the enzyme, as well as the high density of hydrogen bonds it forms with hIDO-1 despite its small size. | ||||||
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Targets |
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In vitro | PF-06840003 is a racemic mixture. The IC50s of PF-06840003 for hIDO-1, mouse IDO-1 and dog IDO-1 are 0.41, 1.5 and 0.59 μM, respectively. It has very weak activity against hTDO-2, with an IC50 of 140 μM. In cellular assays, PF-06840003 shows activity both in the HeLa assay (IC50 1.8 μM) as well as in the LPS/INFγ-stimulated THP1 cells (IC50 1.7 μM). PF-06840003 is a very weak inhibitor of CYPs with IC50 values greater than 100 μM for most major CYP isozymes except 2C19 (IC50 value is 78 μM). Additionally, PF-06840003 does not exhibit metabolism-dependent (time-dependent and NADPH-dependent or time-dependent (NADPH-independent) inhibition of the major CYP enzymes investigated[1]. | ||||||
In vivo | PF-06840003 has a predicted half-life of 16−19 h. Oral bioavailability in the mouse and rat was 59 and 94%, respectively, and 19% in dog. PF-06840003 has shown significant antitumor activity in monotherapy in Pan02, B16−F10, CT26, MC38, 4T1, and Renca models (p < 0.05 vs vehicle-treated group) and very good synergy in combination with anti-PDL1 mAb in CT26 model (p < 0.05 vs monotherapy groups).The PK profile of the compound is excellent, with a low/moderate clearance in most preclinical species. The compound also shows good CNS penetration in rat, suggesting potential impact on brain metastases[1]. |
Cell Assay: |
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Animal Study: |
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25-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent [ Front Immunol, 2023, 14:1100041] | PubMed: 36761739 |
System analysis based on the cancer-immunity cycle identifies ZNF207 as a novel immunotherapy target for hepatocellular carcinoma [ J Immunother Cancer, 2022, 10(3)e004414] | PubMed: 35246476 |
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression [ Cell, 2020, 182(5):1252-1270.e34] | PubMed: 32818467 |
Pleiotropic effects of vitamin D3 on CD4+ T lymphocytes mediated by human periodontal ligament cells and inflammatory environment. [ J Clin Periodontol, 2020, 10.1111/jcpe.13283] | PubMed: 32160330 |
Cytokines Differently Define the Immunomodulation of Mesenchymal Stem Cells From the Periodontal Ligament [ Cells, 2020, 14;9(5):E1222] | PubMed: 32423044 |
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.