PF-04981517 | CYP3cide | CAS# 1390637-82-7 | CYP3A4 Inactivator

MedKoo Cat#: 551013 | Name: PF-04981517

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Description:

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

PF-04981517, also known as CYP3cide, is a potent and selective time dependent inactivator of Cytochrome P450 3A4 (CYP3A4). CYP3cide is a very useful tool for understanding the relative roles of CYP3A4 versus CYP3A5 and the impact of CYP3A5 genetic polymorphism on a compound's pharmacokinetics.

Chemical Structure

PF-04981517

CAS#1390637-82-7

Theoretical Analysis

MedKoo Cat#: 551013

Name: PF-04981517

CAS#: 1390637-82-7

Chemical Formula: C26H32N8

Exact Mass: 456.2750

Molecular Weight: 456.60

Elemental Analysis: C, 68.39; H, 7.06; N, 24.54

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 285.00	2 Weeks
50mg	USD 870.00	2 Weeks

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Related CAS #

1390637-82-7

Synonym

CYP3cide, PF-4981517; PF-04981517; PF 04981517; PF04981517.

IUPAC/Chemical Name

1-Methyl-3-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-[(3S)-3-piperidin-1-ylpyrrolidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine

InChi Key

WDWIMDKOXZZYHH-FQEVSTJZSA-N

InChi Code

InChI=1S/C26H32N8/c1-18-7-9-19(10-8-18)24-21(15-29-31(24)2)23-22-25(32(3)30-23)27-17-28-26(22)34-14-11-20(16-34)33-12-5-4-6-13-33/h7-10,15,17,20H,4-6,11-14,16H2,1-3H3/t20-/m0/s1

SMILES Code

CC1=CC=C(C2=C(C3=NN(C)C4=NC=NC(N5C[C@@H](N6CCCCC6)CC5)=C43)C=NN2C)C=C1

Appearance

white to beige 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

Certificate of Analysis

View CoA: current batch, Lot#C8M03C21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

CYP3cide (PF-4981517) is a potent, selective and time-dependent inhibitor of cytochrome P4503A4 (CYP3A4).

In vitro activity:

CYP3cide (PF-4981517; 1-methyl-3-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-[(3S)-3-piperidin-1-ylpyrrolidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine) is a potent, efficient, and specific time-dependent inactivator of human CYP3A4. When investigating its inhibitory properties, an extreme metabolic inactivation efficiency (k(inact)/K(I)) of 3300 to 3800 ml · min⁻¹ · μmol⁻¹ was observed using human liver microsomes from donors of nonfunctioning CYP3A5 (CYP3A5 *3/*3). This observed efficiency equated to an apparent K(I) between 420 and 480 nM with a maximal inactivation rate (k(inact)) equal to 1.6 min⁻¹. Reference: Drug Metab Dispos. 2012 Sep;40(9):1686-97. https://pubmed.ncbi.nlm.nih.gov/22645092/

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	65.70
	DMF:PBS (pH 7.2) (1:1)	0.5	1.10
	DMSO	55.5	121.55
	Ethanol	2.0	4.38

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 456.60 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:

Walsky RL, Obach RS, Hyland R, Kang P, Zhou S, West M, Geoghegan KF, Helal CJ, Walker GS, Goosen TC, Zientek MA. Selective mechanism-based inactivation of CYP3A4 by CYP3cide (PF-04981517) and its utility as an in vitro tool for delineating the relative roles of CYP3A4 versus CYP3A5 in the metabolism of drugs. Drug Metab Dispos. 2012 Sep;40(9):1686-97. doi: 10.1124/dmd.112.045302. Epub 2012 May 29. PMID: 22645092.

In vitro protocol:

In vivo protocol:

TBD

1: Work HM, Kandel SE, Lampe JN. Comparison of the CYP3A selective inhibitors CYP3cide, clobetasol, and azamulin for their potential to distinguish CYP3A7 activity in the presence of CYP3A4/5. Drug Metab Dispos. 2024 May 3:DMD- AR-2023-001598. doi: 10.1124/dmd.124.001598. Epub ahead of print. PMID: 38702193. 2: Chanteux H, Rosa M, Delatour C, Nicolaï J, Gillent E, Dell'Aiera S, Ungell AL. Application of Azamulin to Determine the Contribution of CYP3A4/5 to Drug Metabolic Clearance Using Human Hepatocytes. Drug Metab Dispos. 2020 Sep;48(9):778-787. doi: 10.1124/dmd.120.000017. Epub 2020 Jun 12. PMID: 32532738. 3: Tseng E, Fate GD, Walker GS, Goosen TC, Obach RS. Biosynthesis and Identification of Metabolites of Maraviroc and Their Use in Experiments to Delineate the Relative Contributions of Cytochrome P4503A4 versus 3A5. Drug Metab Dispos. 2018 May;46(5):493-502. doi: 10.1124/dmd.117.079855. Epub 2018 Feb 23. PMID: 29475834. 4: Dorr CR, Remmel RP, Muthusamy A, Fisher J, Moriarity BS, Yasuda K, Wu B, Guan W, Schuetz EG, Oetting WS, Jacobson PA, Israni AK. CRISPR/Cas9 Genetic Modification of CYP3A5 *3 in HuH-7 Human Hepatocyte Cell Line Leads to Cell Lines with Increased Midazolam and Tacrolimus Metabolism. Drug Metab Dispos. 2017 Aug;45(8):957-965. doi: 10.1124/dmd.117.076307. Epub 2017 May 22. PMID: 28533324; PMCID: PMC5518718. 5: Verbueken E, Alsop D, Saad MA, Pype C, Van Peer EM, Casteleyn CR, Van Ginneken CJ, Wilson J, Van Cruchten SJ. In Vitro Biotransformation of Two Human CYP3A Probe Substrates and Their Inhibition during Early Zebrafish Development. Int J Mol Sci. 2017 Jan 22;18(1):217. doi: 10.3390/ijms18010217. PMID: 28117738; PMCID: PMC5297846. 6: Zhuang X, Zhang T, Yue S, Wang J, Luo H, Zhang Y, Li Z, Che J, Yang H, Li H, Zhu M, Lu C. Allosteric activation of midazolam CYP3A5 hydroxylase activity by icotinib - Enhancement by ketoconazole. Biochem Pharmacol. 2016 Dec 1;121:67-77. doi: 10.1016/j.bcp.2016.09.012. Epub 2016 Sep 22. PMID: 27666601. 7: Towles JK, Clark RN, Wahlin MD, Uttamsingh V, Rettie AE, Jackson KD. Cytochrome P450 3A4 and CYP3A5-Catalyzed Bioactivation of Lapatinib. Drug Metab Dispos. 2016 Oct;44(10):1584-97. doi: 10.1124/dmd.116.070839. Epub 2016 Jul 22. PMID: 27450182; PMCID: PMC5034700. 8: Yang X, Atkinson K, Di L. Novel Cytochrome P450 Reaction Phenotyping for Low- Clearance Compounds Using the Hepatocyte Relay Method. Drug Metab Dispos. 2016 Mar;44(3):460-5. doi: 10.1124/dmd.115.067876. Epub 2015 Dec 23. PMID: 26700955. 9: Zientek MA, Goosen TC, Tseng E, Lin J, Bauman JN, Walker GS, Kang P, Jiang Y, Freiwald S, Neul D, Smith BJ. In Vitro Kinetic Characterization of Axitinib Metabolism. Drug Metab Dispos. 2016 Jan;44(1):102-14. doi: 10.1124/dmd.115.065615. Epub 2015 Oct 28. PMID: 26512042. 10: Van Peer E, De Bock L, Boussery K, Van Bocxlaer J, Casteleyn C, Van Ginneken C, Van Cruchten S. Age-related Differences in CYP3A Abundance and Activity in the Liver of the Göttingen Minipig. Basic Clin Pharmacol Toxicol. 2015 Nov;117(5):350-7. doi: 10.1111/bcpt.12410. Epub 2015 May 18. PMID: 25892190. 11: Tseng E, Walsky RL, Luzietti RA Jr, Harris JJ, Kosa RE, Goosen TC, Zientek MA, Obach RS. Relative contributions of cytochrome CYP3A4 versus CYP3A5 for CYP3A-cleared drugs assessed in vitro using a CYP3A4-selective inactivator (CYP3cide). Drug Metab Dispos. 2014 Jul;42(7):1163-73. doi: 10.1124/dmd.114.057000. Epub 2014 Apr 15. PMID: 24737844. 12: Zhu Y, Wang F, Li Q, Zhu M, Du A, Tang W, Chen W. Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation. Drug Metab Dispos. 2014 Feb;42(2):245-9. doi: 10.1124/dmd.113.055400. Epub 2013 Dec 3. PMID: 24301608. 13: Walsky RL, Obach RS, Hyland R, Kang P, Zhou S, West M, Geoghegan KF, Helal CJ, Walker GS, Goosen TC, Zientek MA. Selective mechanism-based inactivation of CYP3A4 by CYP3cide (PF-04981517) and its utility as an in vitro tool for delineating the relative roles of CYP3A4 versus CYP3A5 in the metabolism of drugs. Drug Metab Dispos. 2012 Sep;40(9):1686-97. doi: 10.1124/dmd.112.045302. Epub 2012 May 29. PMID: 22645092.