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PF-06840003 IDO/TDO inhibitor

Name: PF-06840003
Brand: Selleck Chemicals
SKU: S8657
Availability: InStock
Rating: 5 (5 reviews)

Cat.No.S8657

PF-06840003 (EOS200271) is a highly selective orally bioavailable IDO-1 inhibitor. Although this compound 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.

Chemical Structure

Molecular Weight: 232.21

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S865701 DMSO]46 mg/mL]false]Ethanol]6 mg/mL]false]Water]Insoluble]false Purity: 99.97%

99.97

Related Targets	P450 (e.g. CYP17) Dehydrogenase PDE phosphatase PPAR HSP Vitamin Transferase Carbohydrate Metabolism Mitochondrial Metabolism Drug Metabolite Casein Kinase Serine/threonin kinase Lipoxygenase LPL Receptor Phospholipase (e.g. PLA) Retinoid Receptor DPP ACE Peroxidases Amino Acids and Derivatives Fatty Acid Synthase Glucokinase FXR HMG-CoA Reductase Carbonic Anhydrase Lipase Decarboxylase DHFR Hydroxylase
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Chemical Information, Storage & Stability

Molecular Weight	232.21	Formula	C₁₂H₉FN₂O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	198474-05-4	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	EOS200271			Smiles	C1C(C(=O)NC1=O)C2=CNC3=C2C=C(C=C3)F

Solubility

In vitro
Batch:

DMSO : 46 mg/mL (198.09 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 6 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
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 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	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 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	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.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	hIDO-1 ^[1] (Cell-free) 0.41 μM dIDO-1 ^[1] (Cell-free) 0.59 μM mIDO-1 ^[1] (Cell-free) 1.5 μM
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].
References	[1] https://pubmed.ncbi.nlm.nih.gov/29111717/

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