PF-06840003

製品コードS8657 バッチS865701

印刷

化学情報

Synonyms

EOS200271

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₂H₉FN₂O₂

分子量

232.21

CAS No.

198474-05-4

Solubility (25°C)*

体外

DMSO

46 mg/mL (198.09 mM)

Ethanol

6 mg/mL (25.83 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	20.000mg/ml (86.13mM)	Taking the 1 mL working solution as an example, add 50 μL of 400 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.600mg/ml (2.58mM)	Taking the 1 mL working solution as an example, add 50 μL of 12 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
in vitro	PF-06840003 is a racemic mixture. The IC50s of this compound 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, this chemical 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). It 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, it 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. This compound 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. It also shows good CNS penetration in rat, suggesting potential impact on brain metastases^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	HeLa cervical carcinoma cells
	濃度	0-50 μM
	反応時間	16-24 h
	実験の流れ	HeLa cells were harvested from cell culture flasks using 0.25% trypsin/EDTA and neutralized with EMEM growth medium. Following resuspension in fresh growth media, cells were seeded at 20,000 cells per well in 200 μL growth media in a 96-well plate and allowed to adhere at 37 °C at 5% CO2 overnight. The following day, growth media was aspirated and replaced with 200 μL of reduced (2%) serum media containing 100 ng/mL recombinant human interferon gamma (rhIFNγ) and incubated at 37 °C with 5% CO2 for 48 h to induce IDO-1 expression. On day four, this compound was diluted to 10 mM in DMSO and 11-point three-fold dilutions were prepared. rhIFNγ-containing media was removed, and following dilution into EMEM, this chemical was added to cells at 50 μM top concentration and allowed to incubate 16−24 h at 37 °C with 5% CO2. On day five of the assay, 100 μL of cell supernatant was transferred to a v-bottom 96-well plate. Thirty microliters of 30% trichloroacetic acid (TCA) was added to each well to precipitate proteins, and plates were centrifuged at 3000 rpm for 10 min. One hundred microliters was transferred to a fresh flat-bottom 96-well plate, and 100 μL/well of 2% 4-(dimethylamino)benzaldehyde (pDMAB) in acetic acid was added to derivatize N-formyl kynurenine to kynurenine for quantitative colorimetric readout. Assay plates were read at A492 on Envision plate reader.
動物実験	動物モデル	CD-1 mice, Wistar−Han rat, and Beagle dog
	投薬量	1 mg/kg (IV) and 3 mg/kg (oral)
	投与方法	i.v./oral

参考

https://pubmed.ncbi.nlm.nih.gov/29111717/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。