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Purity: ≥98%
PF-9366 (PF9366) is a novel, potent and allosteric inhibitor of human methionine adenosyltransferase 2A (Mat2A) with anticancer activity. It inhibits Mat2A with an IC50 of 420 nM and a Kd of 170 nM. Human methionine adenosyltransferase 2A (Mat2A), the extrahepatic isoform, is often deregulated in cancer. We identified a Mat2A inhibitor, PF-9366, binds an allosteric site on Mat2A that overlaps with the binding site for the Mat2A regulator, Mat2B. Studies exploiting PF-9366 suggested a general mode of Mat2A allosteric regulation. Allosteric binding of PF-9366 or Mat2B altered the Mat2A active site, resulting in increased substrate affinity and decreased enzyme turnover. These data support a model whereby Mat2B functions as an inhibitor of Mat2A activity when methionine or SAM levels are high, yet functions as an activator of Mat2A when methionine or SAM levels are low.
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| ln Vitro |
Mat2A inhibitor PF-9366 has a 420 nM IC50 and a 170 nM Kd. There is no significant off-target action of PF-9366 in phosphodiesterases, ion channels, neurotransporters, or GPCRs. In cancer cells, PF-9366 exhibits inhibitory action against Mat2A. With an IC50 of 1.2 μM, PF-9366 suppresses the synthesis of S-Adenosyl-L-methionine (SAM) in H520 lung cancer cells. With an IC50 of 255 nM, PF-9366 is more effective against SAM synthesis in Huh-7 cells. It also inhibits cell proliferation with an IC50 of 10 μM.
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| References |
| Molecular Formula |
C20H19CLN4
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|---|---|
| Molecular Weight |
350.8447
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| Exact Mass |
350.129
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| CAS # |
72882-78-1
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| PubChem CID |
12612431
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| Appearance |
White to off-white solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
439
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC2=C(C=1)C(C1C=CC=CC=1)=CC1=NN=C(CCN(C)C)N21
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| InChi Key |
LYLASWLQCMKZAT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19ClN4/c1-24(2)11-10-19-22-23-20-13-16(14-6-4-3-5-7-14)17-12-15(21)8-9-18(17)25(19)20/h3-9,12-13H,10-11H2,1-2H3
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| Chemical Name |
2-(7-Chloro-5-phenyl-[1,2,4]triazolo[4,3-a]quinolin-1-yl)-N,N-dimethylethan-1-amine
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| Synonyms |
PF-9366; PF 9366; PF9366.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
DMSO : ~10 mg/mL (~28.50 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.13 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 (7.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8503 mL | 14.2515 mL | 28.5030 mL | |
| 5 mM | 0.5701 mL | 2.8503 mL | 5.7006 mL | |
| 10 mM | 0.2850 mL | 1.4252 mL | 2.8503 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.
 PF-9366 inhibition of Mat2A.Nat Chem Biol.2017 Jul;13(7):785-792. |
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 Structure of the Mat2A–PF-9366 complex that overlaps the Mat2B binding site.Nat Chem Biol.2017 Jul;13(7):785-792. |
 Mat2A ligand induced structural dynamics probed by hydrogen–deuterium exchange mass spectrometry (HDX–MS).Nat Chem Biol.2017 Jul;13(7):785-792. |
 Kinetic consequences of PF-9366 and Mat2B binding.Nat Chem Biol.2017 Jul;13(7):785-792. |
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 PF-9366 and Mat2B modulation of Mat2A in H520 lung cancer cells.Nat Chem Biol.2017 Jul;13(7):785-792. |
 Mat2A is upregulated in response to inhibition. |
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