PF-06840003

別名:EOS200271

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.

PF-06840003化学構造

CAS No. 198474-05-4

サイズ 価格(税別) 在庫状況
JPY 23100 国内在庫あり
JPY 66300 国内在庫あり

代表番号: 045-509-1970|電子メール:[email protected]
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文献中Selleckの製品使用例(5)

製品安全説明書

現在のバッチを見る: S865701 DMSO] 46 mg/mL] false] Ethanol] 6 mg/mL] false] Water] Insoluble] false 純度: 99.97%
99.97

PF-06840003関連製品

IDO/TDO阻害剤の選択性比較

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.
Targets
hIDO-1 [1]
(Cell-free)
dIDO-1 [1]
(Cell-free)
mIDO-1 [1]
(Cell-free)
0.41 μM 0.59 μM 1.5 μM
In Vitro
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].
細胞実験 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, compounds were diluted to 10 mM in DMSO and 11-point three-fold dilutions were prepared. rhIFNγ-containing media was removed, and following dilution into EMEM, compounds were 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.

In Vivo
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].
動物実験 動物モデル CD-1 mice, Wistar−Han rat, and Beagle dog
投与量 1 mg/kg (IV) and 3 mg/kg (oral)
投与経路 i.v./oral

化学情報

分子量 232.21 化学式

C12H9FN2O2
 

CAS No. 198474-05-4 SDF Download PF-06840003 SDFをダウンロードする
Smiles C1C(C(=O)NC1=O)C2=CNC3=C2C=C(C=C3)F
保管

In vitro
Batch:

DMSO : 46 mg/mL ( (198.09 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 6 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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