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Purity: ≥98%
PF-06840003 (also known as PF06840003; EOS200271) is a highly potent and selective, orally bioavailable IDO-1 inhibitor (IC50 of 0.15 μM) with anticancer activity. It is a tryptophan analog, noncompetitive, and non-heme-binding IDO1 inhibitor licensed by iTeos SA to Pfizer for clinical development. Tumors use tryptophan-catabolizing enzymes such as indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of a key immunosuppressive mechanism and represents an important immunotherapeutic target in oncology. PF-06840003 has favorable human pharmacokinetic characteristics, a prolonged human half-life that may allow single-dose daily administration, and CNS penetration. PF-0684000 has moderate hIDO1 enzyme inhibition with IC50 0.41 μM. It is a highly efficient compound which is 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.
| ln Vitro |
In vitro, PF-06840003 reverses T-cell anergy produced by IDO-1[1]. PF-06840003 exhibits action in both the LPS/INFγ-stimulated THP1 cells (IC50=1.7 μM) and the HeLa test (IC50=1.8 μM)[2].
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| ln Vivo |
When combined with immune checkpoint inhibitors, PF-06840003 decreases intratumoral kynurenine levels in mice by >80% and prevents tumor growth in several preclinical syngeneic models in mice. Positively anticipated human pharmacokinetic characteristics for PF-0684003 include a predicted t1/2 of 16–19 hours[1].
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| References |
[1]. Tumang J, et al. PF-06840003: a highly selective IDO-1 inhibitor that shows good in vivo efficacy in combination with immune checkpoint inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr4863.
[2]. Indoleamine 2,3-Dioxygenase (IDO-1) Inhibitor 3-(5-Fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione (EOS200271/PF-06840003) and Its Characterization as a Potential Clinical Candidate. J Med Chem. 2017 Dec 14;60(23):9617-9629. |
| Molecular Formula |
C12H9FN2O2
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| Molecular Weight |
232.21
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| CAS # |
198474-05-4
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| SMILES |
O=C(C(C1=CNC2=C1C=C(F)C=C2)C3)NC3=O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.77 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3064 mL | 21.5322 mL | 43.0645 mL | |
| 5 mM | 0.8613 mL | 4.3064 mL | 8.6129 mL | |
| 10 mM | 0.4306 mL | 2.1532 mL | 4.3064 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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