PF-3845 | CAS#1196109-52-0 | FAAH inhibitor

PF-3845
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 503210

CAS#: 1196109-52-0

Description: PF-3845 is a fatty acid amide hydrolase (FAAH) inhibitor, and acts in the nervous system to reverse LPS-induced tactile allodynia in mice. PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury. Treatment with PF3845 inactivated FAAH activity and enhanced the AEA levels in the brain. It reduced neurodegeneration in the dentate gyrus, and up-regulated the expression of Bcl-2 and Hsp70/72 in both cortex and hippocampus. PF3845 also suppressed the increased production of amyloid precursor protein, prevented dendritic loss and restored the levels of synaptophysin in the ipsilateral dentate gyrus.

Chemical Structure

PF-3845

CAS# 1196109-52-0

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 503210
Name: PF-3845
CAS#: 1196109-52-0
Chemical Formula: C24H23F3N4O2
Exact Mass: 456.18
Molecular Weight: 456.460
Elemental Analysis: C, 63.15; H, 5.08; F, 12.49; N, 12.27; O, 7.01

Price and Availability

Size	Price	Availability
25mg	USD 350	2 Weeks
50mg	USD 550	2 Weeks
100mg	USD 950
200mg	USD 1450
500mg	USD 2850	2 Weeks
1g	USD 3950	2 Weeks
2g	USD 7450	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: PF3845; PF-3845; PF 3845.

IUPAC/Chemical Name: N-3-Pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide

InChi Key: NBOJHRYUGLRASX-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H23F3N4O2/c25-24(26,27)19-6-7-22(29-15-19)33-21-5-1-3-18(14-21)13-17-8-11-31(12-9-17)23(32)30-20-4-2-10-28-16-20/h1-7,10,14-17H,8-9,11-13H2,(H,30,32)

SMILES Code: O=C(N1CCC(CC2=CC=CC(OC3=NC=C(C(F)(F)F)C=C3)=C2)CC1)NC4=CC=CN=C4

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, not soluble in water.

Shelf Life: >5 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: Fatty acid amide hydrolase (FAAH) is an enzyme that catalyzes N-acyl ethanolamines (NAEs), including the endocannabinoid arachidonoyl ethanolamide (AEA). PF-3845. Mechanistic and structural studies confirm that PF-3845 is a covalent inhibitor that carbamylates FAAH's serine nucleophile. PF-3845 selectively inhibits FAAH in vivo, as determined by activity-based protein profiling; raises brain anandamide levels for up to 24 hr; and produces significant cannabinoid receptor-dependent reductions in inflammatory pain. These data thus designate PF-3845 as a valuable pharmacological tool for in vivo characterization of the endocannabinoid system. ( source: Chem Biol. 2009 Apr 24;16(4):411-20 .)

Product Data:

Product Data

Instruction:

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Biological target:	PF-3845 is a potent, selective, irreversible and orally active inhibitor of fatty acid amide hydrolase (FAAH), with a Ki of 0.23 µM.
In vitro activity:	This study found that of all the inhibitors used, the FAAH inhibitor PF-3845 reduced the Colo-205 cell line viability the most effectively (IC50=52.55 μM). This study also showed that the effect of decreased cell viability was enhanced when Colo-205 cells were incubated with PF-3845 and RN-1734, a TRPV4 antagonist (IC50=30.54 μM). Western blot assay revealed significantly decreased CB1 receptor expression levels, while CB2 expression was increased in response to PF-3845 when compared to control. Furthermore, PF-3845 inhibited migration and invasion of Colo-205 cell line. Reference: Acta Biochim Pol. 2017;64(3):519-525. https://pubmed.ncbi.nlm.nih.gov/28850633/
In vivo activity:	FAAH (-/-) mice or wild-type mice treated with FAAH inhibitors (URB597, OL-135 and PF-3845) displayed an anti-allodynic phenotype. Furthermore, i.p. PF-3845 increased AEA levels in the brain and spinal cord. Additionally, intraplantar PF-3845 produced a partial reduction in allodynia. Reference: Br J Pharmacol. 2012 Apr;165(8):2485-96. https://pubmed.ncbi.nlm.nih.gov/21506952/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	20.0	43.82
	DMSO	64.2	140.57
	Ethanol	44.6	97.72
	Ethanol:PBS (pH 7.2) (1:3)	0.3	0.55

Preparing Stock Solutions

The following data is based on the product molecular weight 456.46 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.

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. Wasilewski A, Krajewska U, Owczarek K, Lewandowska U, Fichna J. Fatty acid amide hydrolase (FAAH) inhibitor PF-3845 reduces viability, migration and invasiveness of human colon adenocarcinoma Colo-205 cell line: an in vitro study. Acta Biochim Pol. 2017;64(3):519-525. doi: 10.18388/abp.2017_1520. Epub 2017 Aug 30. PMID: 28850633. 2. Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, Weerapana E, Sadagopan N, Liimatta M, Smith SE, Lazerwith S, Stiff C, Kamtekar S, Bhattacharya K, Zhang Y, Swaney S, Van Becelaere K, Stevens RC, Cravatt BF. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol. 2009 Apr 24;16(4):411-20. doi: 10.1016/j.chembiol.2009.02.013. PMID: 19389627; PMCID: PMC2692831. 3. Ihn HJ, Kim YS, Lim S, Bae JS, Jung JC, Kim YH, Park JW, Wang Z, Koh JT, Bae YC, Baek MC, Park EK. PF-3845, a Fatty Acid Amide Hydrolase Inhibitor, Directly Suppresses Osteoclastogenesis through ERK and NF-κB Pathways In Vitro and Alveolar Bone Loss In Vivo. Int J Mol Sci. 2021 Feb 15;22(4):1915. doi: 10.3390/ijms22041915. PMID: 33671948; PMCID: PMC7919013. 4. Booker L, Kinsey SG, Abdullah RA, Blankman JL, Long JZ, Ezzili C, Boger DL, Cravatt BF, Lichtman AH. The fatty acid amide hydrolase (FAAH) inhibitor PF-3845 acts in the nervous system to reverse LPS-induced tactile allodynia in mice. Br J Pharmacol. 2012 Apr;165(8):2485-96. doi: 10.1111/j.1476-5381.2011.01445.x. PMID: 21506952; PMCID: PMC3423256.
In vitro protocol:	1. Wasilewski A, Krajewska U, Owczarek K, Lewandowska U, Fichna J. Fatty acid amide hydrolase (FAAH) inhibitor PF-3845 reduces viability, migration and invasiveness of human colon adenocarcinoma Colo-205 cell line: an in vitro study. Acta Biochim Pol. 2017;64(3):519-525. doi: 10.18388/abp.2017_1520. Epub 2017 Aug 30. PMID: 28850633. 2. Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, Weerapana E, Sadagopan N, Liimatta M, Smith SE, Lazerwith S, Stiff C, Kamtekar S, Bhattacharya K, Zhang Y, Swaney S, Van Becelaere K, Stevens RC, Cravatt BF. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol. 2009 Apr 24;16(4):411-20. doi: 10.1016/j.chembiol.2009.02.013. PMID: 19389627; PMCID: PMC2692831.
In vivo protocol:	1. Ihn HJ, Kim YS, Lim S, Bae JS, Jung JC, Kim YH, Park JW, Wang Z, Koh JT, Bae YC, Baek MC, Park EK. PF-3845, a Fatty Acid Amide Hydrolase Inhibitor, Directly Suppresses Osteoclastogenesis through ERK and NF-κB Pathways In Vitro and Alveolar Bone Loss In Vivo. Int J Mol Sci. 2021 Feb 15;22(4):1915. doi: 10.3390/ijms22041915. PMID: 33671948; PMCID: PMC7919013. 2. Booker L, Kinsey SG, Abdullah RA, Blankman JL, Long JZ, Ezzili C, Boger DL, Cravatt BF, Lichtman AH. The fatty acid amide hydrolase (FAAH) inhibitor PF-3845 acts in the nervous system to reverse LPS-induced tactile allodynia in mice. Br J Pharmacol. 2012 Apr;165(8):2485-96. doi: 10.1111/j.1476-5381.2011.01445.x. PMID: 21506952; PMCID: PMC3423256.

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1: Ramesh D, Ross GR, Schlosburg JE, Owens RA, Abdullah RA, Kinsey SG, Long JZ, Nomura DK, Sim-Selley LJ, Cravatt BF, Akbarali HI, Lichtman AH. Blockade of endocannabinoid hydrolytic enzymes attenuates precipitated opioid withdrawal symptoms in mice. J Pharmacol Exp Ther. 2011 Oct;339(1):173-85. Epub 2011 Jun 30. PubMed PMID: 21719468; PubMed Central PMCID: PMC3186294.

2: Kinsey SG, Nomura DK, O'Neal ST, Long JZ, Mahadevan A, Cravatt BF, Grider JR, Lichtman AH. Inhibition of monoacylglycerol lipase attenuates nonsteroidal anti-inflammatory drug-induced gastric hemorrhages in mice. J Pharmacol Exp Ther. 2011 Sep;338(3):795-802. Epub 2011 Jun 9. PubMed PMID: 21659471; PubMed Central PMCID: PMC3164340.

3: Booker L, Kinsey SG, Abdullah RA, Blankman JL, Long JZ, Ezzili C, Boger DL, Cravatt BF, Lichtman AH. The FAAH Inhibitor PF-3845 Acts in the Nervous System to Reverse Lipopolysaccharide-induced Tactile Allodynia in Mice. Br J Pharmacol. 2011 Apr 20. doi: 10.1111/j.1476-5381.2011.01445.x. [Epub ahead of print] PubMed PMID: 21506952.

4: Kinsey SG, O'Neal ST, Long JZ, Cravatt BF, Lichtman AH. Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay. Pharmacol Biochem Behav. 2011 Mar;98(1):21-7. Epub 2010 Dec 8. PubMed PMID: 21145341; PubMed Central PMCID: PMC3034086.

5: Long JZ, LaCava M, Jin X, Cravatt BF. An anatomical and temporal portrait of physiological substrates for fatty acid amide hydrolase. J Lipid Res. 2011 Feb;52(2):337-44. Epub 2010 Nov 19. PubMed PMID: 21097653; PubMed Central PMCID: PMC3023554.

6: Kinsey SG, Long JZ, Cravatt BF, Lichtman AH. Fatty acid amide hydrolase and monoacylglycerol lipase inhibitors produce anti-allodynic effects in mice through distinct cannabinoid receptor mechanisms. J Pain. 2010 Dec;11(12):1420-8. Epub 2010 Jun 16. PubMed PMID: 20554481; PubMed Central PMCID: PMC2962430.

7: Mileni M, Kamtekar S, Wood DC, Benson TE, Cravatt BF, Stevens RC. Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation. J Mol Biol. 2010 Jul 23;400(4):743-54. Epub 2010 May 21. PubMed PMID: 20493882; PubMed Central PMCID: PMC3014312.

8: Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, Weerapana E, Sadagopan N, Liimatta M, Smith SE, Lazerwith S, Stiff C, Kamtekar S, Bhattacharya K, Zhang Y, Swaney S, Van Becelaere K, Stevens RC, Cravatt BF. Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol. 2009 Apr 24;16(4):411-20. PubMed PMID: 19389627; PubMed Central PMCID: PMC2692831.

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