| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
PF-04859989 targets kynurenine aminotransferase II (KAT II), a pyridoxal-5′-phosphate (PLP)-dependent enzyme responsible for the majority of brain KYNA synthesis. It has IC50s of 23 nM (0.032 µM) and 263 nM (0.263 µM) for human and rat recombinant KAT II, respectively. It is selective for KAT II over KAT I, -III, and -IV (IC50s = 21.6, 107, and >50 µM, respectively).
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| ln Vitro |
In vitro, PF-04859989 demonstrates potent and selective inhibition of KAT II with IC50s of 23 nM for human KAT II and 263 nM for rat KAT II. It shows selectivity for KAT II over KAT I, -III, and -IV, with IC50 values of 21.6, 107, and >50 µM, respectively. The compound also inhibits glutamate oxaloacetate transaminase 1 (GOT1; IC50 = 8 µM).
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| ln Vivo |
PF-04859989 is a brain-penetrating, irreversible inhibitor that decreases brain kynurenic acid by 50% at a dose of 10 mg/kg (sc) according to in vivo pharmacokinetic and effectiveness tests conducted in rats [1]. PF-04859989 (5 mg/kg; i.p.)-treated rats displayed a marked decrease in the quantity of spontaneously activated DA neurons per trajectory [1].
In vivo, PF-04859989 (10 mg/kg, s.c.) reduces basal striatum, prefrontal cortex, and hippocampus kynurenic acid levels in rats. It prevents ketamine- or amphetamine-induced disruption of auditory gating in rats, as well as ketamine-induced deficits in spatial memory in non-human primates. Brain KYNA is reduced by 50% at a dose of 10 mg/kg (s.c.). |
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for PF-04859989 involve KAT II enzyme activity assays. IC50 values are determined using recombinant human and rat KAT II enzymes with appropriate substrates. Selectivity is confirmed by testing against KAT I, -III, and -IV. Inhibition is irreversible, as confirmed by enzyme pre-incubation and dilution experiments.
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| Cell Assay |
In vitro cell-based assays for PF-04859989 use cell lines expressing KAT II to assess enzyme inhibition. The compound's effects on KYNA production are measured in cell culture supernatants. GOT1 inhibition (IC50 = 8 µM) and concentration-dependent reduction of PaTu 8988t and PaTu 8902 pancreatic cancer cell viability are also evaluated.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [2]
Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: The number of spontaneously active dopamine (DA) neurons per track was Dramatically diminished compared with the control. In vivo animal studies for PF-04859989 have been conducted in rats and non-human primates. In rats, subcutaneous administration at 10 mg/kg reduces KYNA levels in striatum, prefrontal cortex, and hippocampus. The compound prevents ketamine- or amphetamine-induced disruption of auditory gating in rats and ketamine-induced spatial memory deficits in non-human primates. |
| ADME/Pharmacokinetics |
PF-04859989 HCl has a molecular formula of C9H10N2O2·HCl and a molecular weight of 214.65 g/mol. The IUPAC name is (3S)-3-amino-1-hydroxy-3,4-dihydroquinolin-2(1H)-one hydrochloride. It is soluble in DMSO and water at 22 mg/mL. Purity is ≥98%. Storage: -20°C. The compound is brain-penetrant.
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| Toxicity/Toxicokinetics |
Specific toxicological data for PF-04859989 are not detailed in the available literature. The compound is classified for research use only and is not intended for human therapeutic applications. WARNING: This product is not for human or veterinary use. As a KAT II inhibitor that modulates brain KYNA levels, potential toxicities would relate to effects on glutamatergic and dopaminergic neurotransmission.
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| References |
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| Additional Infomation |
PF-04859989 HCl (CAS 177943-33-8) is a brain-penetrant, irreversible KAT II inhibitor with IC50s of 23 nM (human) and 263 nM (rat). It is selective for KAT II over KAT I, -III, and -IV. In vivo, it reduces brain KYNA levels and prevents ketamine-induced cognitive deficits. The compound is used in schizophrenia and bipolar disorder research. No clinical trial data are available.
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| Molecular Formula |
C9H10N2O2.HCL
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| Molecular Weight |
214.64884
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| Exact Mass |
214.051
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| CAS # |
177943-33-8
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| Related CAS # |
56433-01-3 (PF-04859989); 177943-33-8 (PF-04859989 HCl);
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| PubChem CID |
22868922
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| Appearance |
White to off-white solid powder
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| LogP |
1.859
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
14
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| Complexity |
220
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1[C@@H](C(=O)N(C2=CC=CC=C21)O)N.Cl
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| InChi Key |
WZOBDOKCHIUXAY-FJXQXJEOSA-N
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| InChi Code |
InChI=1S/C9H10N2O2.ClH/c10-7-5-6-3-1-2-4-8(6)11(13)9(7)12;/h1-4,7,13H,5,10H2;1H/t7-;/m0./s1
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| Chemical Name |
(3S)-3-amino-1-hydroxy-3,4-dihydroquinolin-2-one;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~100 mg/mL (~465.87 mM)
DMSO : ~20.83 mg/mL (~97.04 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.65 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 (11.65 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 (11.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (232.94 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.6587 mL | 23.2937 mL | 46.5875 mL | |
| 5 mM | 0.9317 mL | 4.6587 mL | 9.3175 mL | |
| 10 mM | 0.4659 mL | 2.3294 mL | 4.6587 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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