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MedKoo Cat#: 532461 | Name: PF-04859989 HCl
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PF-04859989 HCl is a brain-penetrable irreversible inhibitor of kynurenine amino transferase II (KAT II), the enzyme responsible for most of the brain synthesis of kynurenic acid. PF-04859989 HCl has been implicated in several psychiatric and neurological disorders, including schizophrenia and bipolar disorder.

Chemical Structure

PF-04859989 HCl
CAS#177943-33-8 (PF-04859989 HCl)

Theoretical Analysis

MedKoo Cat#: 532461

Name: PF-04859989 HCl

CAS#: 177943-33-8 (PF-04859989 HCl)

Chemical Formula: C7H6BrCl2NO2

Exact Mass: 0.0000

Molecular Weight: 286.93

Elemental Analysis: C, 29.30; H, 2.11; Br, 27.85; Cl, 24.71; N, 4.88; O, 11.15

Price and Availability

Size Price Availability Quantity
10mg USD 300.00 2 Weeks
50mg USD 950.00 2 Weeks
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Related CAS #
56433-01-3 (PF-04859989); 177943-33-8 (PF-04859989 HCl)
Synonym
PF-04859989 HCl; PF-04859989HCl; PF-04859989; PF 04859989; PF04859989.
IUPAC/Chemical Name
2-(Bromomethyl)-1-chloro-3-nitrobenzene HCl
InChi Key
MVBWOEUQKOAQOW-UHFFFAOYSA-N
InChi Code
InChI=1S/C7H5BrClNO2.ClH/c8-4-5-6(9)2-1-3-7(5)10(11)12;/h1-3H,4H2;1H
SMILES Code
O=[N+](C1=C(CBr)C(Cl)=CC=C1)[O-].[H]Cl
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PF-04859989 hydrochloride is a brain-penetrant, irreversible kynurenine aminotransferase (KAT) II inhibitor with IC50s of 23 and 263 nM for hKAT II and rKAT II.
In vitro activity:
PF-04859989 significantly facilitated the fEPSP slope in the hippocampal slices from the KMO−/− mice (Figure 5; n = 5; P < .05, unpaired t-test). PF-04859989 also facilitated LTP generated in hippocampal slices from the KMO−/− mice, but already after 5 minutes (Figure 6B, P < .05, unpaired t-test; n = 5) of drug administration, and the effect sustained more than 30 minutes. Reference: Int J Tryptophan Res. 2021 Aug 30;14:11786469211041368. https://pubmed.ncbi.nlm.nih.gov/34483669/
In vivo activity:
The present in vivo electrophysiological study in rats aimed to investigate the effect of an inhibitor of kynurenine aminotransferase (KAT) II, the primary enzyme for KYNA synthesis, on dopamine (DA) neurons in the ventral tegmental area (VTA). Acute administration of the KAT II inhibitor PF-04859989 (5 or 10 mg/kg) was associated with a short-onset, time-dependent decrease in firing rate and burst activity of DA neurons, both parameters reaching a 50% reduction within 45 min. Furthermore, PF-04859989 reduced the number of spontaneously active DA cells as measured 4-6 after administration. Pretreatment with d-cycloserine (30 mg/kg) or CGP-52432 (10 mg/kg) prevented the inhibitory action of PF-04859989 (5 mg/kg) on firing rate and burst firing activity. Reference: Neuropharmacology. 2016 Mar;102:42-7. https://pubmed.ncbi.nlm.nih.gov/26514401/
Solvent mg/mL mM comments
Solubility
DMSO 36.0 125.46
Water 61.0 212.59
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 286.93 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Imbeault S, Gubert Olivé M, Jungholm O, Erhardt S, Wigström H, Engberg G, Jardemark K. Blockade of KAT II Facilitates LTP in Kynurenine 3-Monooxygenase Depleted Mice. Int J Tryptophan Res. 2021 Aug 30;14:11786469211041368. doi: 10.1177/11786469211041368. PMID: 34483669; PMCID: PMC8411644. 2. Dounay AB, Anderson M, Bechle BM, Campbell BM, Claffey MM, Evdokimov A, Evrard E, Fonseca KR, Gan X, Ghosh S, Hayward MM, Horner W, Kim JY, McAllister LA, Pandit J, Paradis V, Parikh VD, Reese MR, Rong S, Salafia MA, Schuyten K, Strick CA, Tuttle JB, Valentine J, Wang H, Zawadzke LE, Verhoest PR. Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia. ACS Med Chem Lett. 2012 Jan 25;3(3):187-92. doi: 10.1021/ml200204m. PMID: 24900455; PMCID: PMC4025856. 3. Klausing AD, Fukuwatari T, Bucci DJ, Schwarcz R. Stress-induced impairment in fear discrimination is causally related to increased kynurenic acid formation in the prefrontal cortex. Psychopharmacology (Berl). 2020 Jul;237(7):1931-1941. doi: 10.1007/s00213-020-05507-x. Epub 2020 Mar 25. PMID: 32215686; PMCID: PMC7308198. 4. Linderholm KR, Alm MT, Larsson MK, Olsson SK, Goiny M, Hajos M, Erhardt S, Engberg G. Inhibition of kynurenine aminotransferase II reduces activity of midbrain dopamine neurons. Neuropharmacology. 2016 Mar;102:42-7. doi: 10.1016/j.neuropharm.2015.10.028. Epub 2015 Oct 24. PMID: 26514401.
In vitro protocol:
1. Imbeault S, Gubert Olivé M, Jungholm O, Erhardt S, Wigström H, Engberg G, Jardemark K. Blockade of KAT II Facilitates LTP in Kynurenine 3-Monooxygenase Depleted Mice. Int J Tryptophan Res. 2021 Aug 30;14:11786469211041368. doi: 10.1177/11786469211041368. PMID: 34483669; PMCID: PMC8411644. 2. Dounay AB, Anderson M, Bechle BM, Campbell BM, Claffey MM, Evdokimov A, Evrard E, Fonseca KR, Gan X, Ghosh S, Hayward MM, Horner W, Kim JY, McAllister LA, Pandit J, Paradis V, Parikh VD, Reese MR, Rong S, Salafia MA, Schuyten K, Strick CA, Tuttle JB, Valentine J, Wang H, Zawadzke LE, Verhoest PR. Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia. ACS Med Chem Lett. 2012 Jan 25;3(3):187-92. doi: 10.1021/ml200204m. PMID: 24900455; PMCID: PMC4025856.
In vivo protocol:
1. Klausing AD, Fukuwatari T, Bucci DJ, Schwarcz R. Stress-induced impairment in fear discrimination is causally related to increased kynurenic acid formation in the prefrontal cortex. Psychopharmacology (Berl). 2020 Jul;237(7):1931-1941. doi: 10.1007/s00213-020-05507-x. Epub 2020 Mar 25. PMID: 32215686; PMCID: PMC7308198. 2. Linderholm KR, Alm MT, Larsson MK, Olsson SK, Goiny M, Hajos M, Erhardt S, Engberg G. Inhibition of kynurenine aminotransferase II reduces activity of midbrain dopamine neurons. Neuropharmacology. 2016 Mar;102:42-7. doi: 10.1016/j.neuropharm.2015.10.028. Epub 2015 Oct 24. PMID: 26514401.
1: Lu J, Zhang Y, Hao Q, Zhou H, Zong Y. IDO-Kynurenine pathway mediates NLRP3 inflammasome activation-induced postoperative cognitive impairment in aged mice. Int J Neurosci. 2023 Sep 25:1-11. doi: 10.1080/00207454.2023.2262741. Epub ahead of print. PMID: 37746906. 2: Rentschler KM, Milosavljevic S, Baratta AM, Wright CJ, Piroli MV, Tentor Z, Valafar H, O'Reilly C, Pocivavsek A. Reducing brain kynurenic acid synthesis precludes kynurenine-induced sleep disturbances. J Sleep Res. 2024 May;33(3):e14038. doi: 10.1111/jsr.14038. Epub 2023 Sep 7. PMID: 37678806; PMCID: PMC10918043. 3: Milosavljevic S, Smith AK, Wright CJ, Valafar H, Pocivavsek A. Kynurenine aminotransferase II inhibition promotes sleep and rescues impairments induced by neurodevelopmental insult. Transl Psychiatry. 2023 Mar 31;13(1):106. doi: 10.1038/s41398-023-02399-1. PMID: 37002202; PMCID: PMC10066394. 4: Beggiato S, Ieraci A, Zuccarini M, Di Iorio P, Schwarcz R, Ferraro L. Alterations in rat prefrontal cortex kynurenic acid levels are involved in the enduring cognitive dysfunctions induced by tetrahydrocannabinol exposure during the adolescence. Front Psychiatry. 2022 Nov 22;13:996406. doi: 10.3389/fpsyt.2022.996406. PMID: 36483135; PMCID: PMC9722723. 5: Imbeault S, Gubert Olivé M, Jungholm O, Erhardt S, Wigström H, Engberg G, Jardemark K. Blockade of KAT II Facilitates LTP in Kynurenine 3-Monooxygenase Depleted Mice. Int J Tryptophan Res. 2021 Aug 30;14:11786469211041368. doi: 10.1177/11786469211041368. PMID: 34483669; PMCID: PMC8411644. 6: Wang D, Li D, Zhang Y, Chen J, Zhang Y, Liao C, Qin S, Tian Y, Zhang Z, Xu F. Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage. Acta Pharm Sin B. 2021 Mar;11(3):763-780. doi: 10.1016/j.apsb.2020.07.017. Epub 2020 Jul 30. PMID: 33777681; PMCID: PMC7982426. 7: Noorbakhsh A, Hosseininezhadian Koushki E, Farshadfar C, Ardalan N. Designing a natural inhibitor against human kynurenine aminotransferase type II and a comparison with PF-04859989: a computational effort against schizophrenia. J Biomol Struct Dyn. 2022 Sep;40(15):7038-7051. doi: 10.1080/07391102.2021.1893817. Epub 2021 Mar 1. PMID: 33645449. 8: Klausing AD, Fukuwatari T, Bucci DJ, Schwarcz R. Stress-induced impairment in fear discrimination is causally related to increased kynurenic acid formation in the prefrontal cortex. Psychopharmacology (Berl). 2020 Jul;237(7):1931-1941. doi: 10.1007/s00213-020-05507-x. Epub 2020 Mar 25. PMID: 32215686; PMCID: PMC7308198. 9: Yoshida T, Yamasaki S, Kaneko O, Taoka N, Tomimoto Y, Namatame I, Yahata T, Kuromitsu S, Cantley LC, Lyssiotis CA. A covalent small molecule inhibitor of glutamate-oxaloacetate transaminase 1 impairs pancreatic cancer growth. Biochem Biophys Res Commun. 2020 Feb 12;522(3):633-638. doi: 10.1016/j.bbrc.2019.11.130. Epub 2019 Nov 28. PMID: 31787239; PMCID: PMC6981064. 10: Zakhary G, Sherchan P, Li Q, Tang J, Zhang JH. Modification of kynurenine pathway via inhibition of kynurenine hydroxylase attenuates surgical brain injury complications in a male rat model. J Neurosci Res. 2020 Jan;98(1):155-167. doi: 10.1002/jnr.24489. Epub 2019 Jun 30. PMID: 31257634; PMCID: PMC6854312. 11: Herédi J, Cseh EK, Berkó AM, Veres G, Zádori D, Toldi J, Kis Z, Vécsei L, Ono E, Gellért L. Investigating KYNA production and kynurenergic manipulation on acute mouse brain slice preparations. Brain Res Bull. 2019 Mar;146:185-191. doi: 10.1016/j.brainresbull.2018.12.014. Epub 2019 Jan 9. PMID: 30639278. 12: Chang C, Fonseca KR, Li C, Horner W, Zawadzke LE, Salafia MA, Welch KA, Strick CA, Campbell BM, Gernhardt SS, Rong H, Sawant-Basak A, Liras J, Dounay A, Tuttle JB, Verhoest P, Maurer TS. Quantitative Translational Analysis of Brain Kynurenic Acid Modulation via Irreversible Kynurenine Aminotransferase II Inhibition. Mol Pharmacol. 2018 Aug;94(2):823-833. doi: 10.1124/mol.118.111625. Epub 2018 May 31. PMID: 29853495. 13: Nematollahi A, Sun G, Jayawickrama GS, Hanrahan JR, Church WB. Study of the Activity and Possible Mechanism of Action of a Reversible Inhibitor of Recombinant Human KAT-2: A Promising Lead in Neurodegenerative and Cognitive Disorders. Molecules. 2016 Jun 29;21(7):856. doi: 10.3390/molecules21070856. PMID: 27367665; PMCID: PMC6273595. 14: Linderholm KR, Alm MT, Larsson MK, Olsson SK, Goiny M, Hajos M, Erhardt S, Engberg G. Inhibition of kynurenine aminotransferase II reduces activity of midbrain dopamine neurons. Neuropharmacology. 2016 Mar;102:42-7. doi: 10.1016/j.neuropharm.2015.10.028. Epub 2015 Oct 24. PMID: 26514401. 15: Kozak R, Campbell BM, Strick CA, Horner W, Hoffmann WE, Kiss T, Chapin DS, McGinnis D, Abbott AL, Roberts BM, Fonseca K, Guanowsky V, Young DA, Seymour PA, Dounay A, Hajos M, Williams GV, Castner SA. Reduction of brain kynurenic acid improves cognitive function. J Neurosci. 2014 Aug 6;34(32):10592-602. doi: 10.1523/JNEUROSCI.1107-14.2014. PMID: 25100593; PMCID: PMC6802596. 16: Koshy Cherian A, Gritton H, Johnson DE, Young D, Kozak R, Sarter M. A systemically-available kynurenine aminotransferase II (KAT II) inhibitor restores nicotine-evoked glutamatergic activity in the cortex of rats. Neuropharmacology. 2014 Jul;82:41-8. doi: 10.1016/j.neuropharm.2014.03.004. Epub 2014 Mar 16. PMID: 24647121; PMCID: PMC4372264. 17: Dounay AB, Anderson M, Bechle BM, Evrard E, Gan X, Kim JY, McAllister LA, Pandit J, Rong S, Salafia MA, Tuttle JB, Zawadzke LE, Verhoest PR. PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency. Bioorg Med Chem Lett. 2013 Apr 1;23(7):1961-6. doi: 10.1016/j.bmcl.2013.02.039. Epub 2013 Feb 15. PMID: 23466229. 18: Dounay AB, Anderson M, Bechle BM, Campbell BM, Claffey MM, Evdokimov A, Evrard E, Fonseca KR, Gan X, Ghosh S, Hayward MM, Horner W, Kim JY, McAllister LA, Pandit J, Paradis V, Parikh VD, Reese MR, Rong S, Salafia MA, Schuyten K, Strick CA, Tuttle JB, Valentine J, Wang H, Zawadzke LE, Verhoest PR. Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia. ACS Med Chem Lett. 2012 Jan 25;3(3):187-92. doi: 10.1021/ml200204m. PMID: 24900455; PMCID: PMC4025856.

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