PFI-3
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MedKoo CAT#: 407284

CAS#: 1819363-80-8

Description: PFI-3 is a potent and selective SMARCA2/4 bromodomain inhibitor that binds avidly to the structurally-similar SMARCA4 bromodomain and PB1(bromodomain with Kd values of 89 and 48 nM, respectively. PFI-3 is a potent, cell-permeable probe capable of displacing ectopically expressed, GFP-tagged SMARCA2-bromodomain from chromatin.

Chemical Structure

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PFI-3
CAS# 1819363-80-8
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 407284
Name: PFI-3
CAS#: 1819363-80-8
Chemical Formula: C19H19N3O2
Exact Mass: 321.15
Molecular Weight: 321.380
Elemental Analysis: C, 71.01; H, 5.96; N, 13.08; O, 9.96

Price and Availability

Size Price Availability Quantity
25mg USD 250 2 Weeks
50mg USD 450 2 Weeks
100mg USD 750 2 Weeks
200mg USD 1250 2 Weeks
500mg USD 2650 2 Weeks
1g USD 3850 2 Weeks
2g USD 6450 2 Weeks
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Synonym: PFI-3; PFI 3; PFI3.

IUPAC/Chemical Name: (E)-1-(2-hydroxyphenyl)-3-((1R,4R)-5-(pyridin-2-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)prop-2-en-1-one

InChi Key: INAICWLVUAKEPB-QSTFCLMHSA-N

InChi Code: InChI=1S/C19H19N3O2/c23-17-6-2-1-5-16(17)18(24)8-10-21-12-15-11-14(21)13-22(15)19-7-3-4-9-20-19/h1-10,14-15,23H,11-13H2/b10-8+/t14-,15-/m1/s1

SMILES Code: OC1=C(C(/C=C/N2[C@H](C3)CN(C4=NC=CC=C4)[C@H]3C2)=O)C=CC=C1

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 in water

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: SMARCA4 (SWI/SNF related, Matrix associated, Actin dependent Regulator of Chromatin, subfamily A, member 4), also known as BRG1 (Brahma-Related Gene 1), is part of the SWI/SNF (SWItch/Sucrose NonFermentable) family of proteins. Multiple transcript variants encoding different isoforms have been found for this gene in normal tissue as well as in cancer. SMARCA4 and the related protein SMARCA2 (BRM, BRahMa) contain a bromo and helicase domain and both proteins are central components of the large ATP-dependent SNF/SWI chromatin remodelling complex, which plays a key role in chromatin remodelling and transcription control. PB1 (PolyBromo 1) can also be part of the SWI/SNF complex. Loss of function of SMARCA4 and components of SWI/SNF has been linked to cancer development suggesting a tumour suppressor function for BRG1. SMARCA4 has also been shown to interact with the breast cancer gene BRCA1 (BReast CAncer 1, early onset), as well as to regulate the expression of the tumorigenic protein CD44. (http://www.thesgc.org/chemical-probes/PFI-3)

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: PFI-3 is a selective, potent and cell-permeable SMARCA2/4 bromodomain inhibitor with a Kd of 89 nM.
In vitro activity: The high specificity of PFI-3 was achieved on the basis of a novel binding mode of a salicylic acid head group that led to the replacement of water molecules typically maintained in other bromodomain inhibitor complexes. This study shows that exposure of embryonic stem cells to PFI-3 led to deprivation of stemness and deregulated lineage specification. Furthermore, differentiation of trophoblast stem cells in the presence of PFI-3 was markedly enhanced. Reference: Sci Adv. 2015 Nov 13;1(10):e1500723. https://pubmed.ncbi.nlm.nih.gov/26702435/
In vivo activity: To test this idea, the mice were induced to develop ALD by the NIAAA procedure followed by injection with a specific Brg1 inhibitor (PFI‐3) or a specific antagonist to the CXCL14 receptor (AMD3100) (Fig 6A). Administration of PFI‐3 significantly alleviated alcoholic liver injury as evidenced by plasma ALT levels (Fig 6B), plasma AST levels (Fig 6C), and hepatic triglyceride levels (Fig 6D). Further evidence that Brg1 inhibition by PFI‐3 administration could potentially mitigate alcoholic liver injury was provided by histological stainings that showed reduced lipid droplets, ROS production, and neutrophil infiltration in the liver (Fig 6 E). Reference: EMBO Mol Med. 2023 Mar 8;15(3):e16592. https://pubmed.ncbi.nlm.nih.gov/36722664/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 25.0 77.79
DMSO 61.5 191.47
DMSO:PBS (pH 7.2) (1:5) 0.2 0.47
Ethanol 0.3 0.93

Preparing Stock Solutions

The following data is based on the product molecular weight 321.38 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. Gerstenberger BS, Trzupek JD, Tallant C, Fedorov O, Filippakopoulos P, Brennan PE, Fedele V, Martin S, Picaud S, Rogers C, Parikh M, Taylor A, Samas B, O'Mahony A, Berg E, Pallares G, Torrey AD, Treiber DK, Samardjiev IJ, Nasipak BT, Padilla-Benavides T, Wu Q, Imbalzano AN, Nickerson JA, Bunnage ME, Müller S, Knapp S, Owen DR. Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit. J Med Chem. 2016 May 26;59(10):4800-11. doi: 10.1021/acs.jmedchem.6b00012. Epub 2016 May 3. PMID: 27115555; PMCID: PMC5034155. 2. Fedorov O, Castex J, Tallant C, Owen DR, Martin S, Aldeghi M, Monteiro O, Filippakopoulos P, Picaud S, Trzupek JD, Gerstenberger BS, Bountra C, Willmann D, Wells C, Philpott M, Rogers C, Biggin PC, Brennan PE, Bunnage ME, Schüle R, Günther T, Knapp S, Müller S. Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance. Sci Adv. 2015 Nov 13;1(10):e1500723. doi: 10.1126/sciadv.1500723. PMID: 26702435; PMCID: PMC4681344. 3. Li N, Liu H, Xue Y, Xu Z, Miao X, Guo Y, Li Z, Fan Z, Xu Y. Targetable Brg1-CXCL14 axis contributes to alcoholic liver injury by driving neutrophil trafficking. EMBO Mol Med. 2023 Mar 8;15(3):e16592. doi: 10.15252/emmm.202216592. Epub 2023 Feb 1. PMID: 36722664; PMCID: PMC9994483. 4. Wu T, Kong M, Xin XJ, Liu RQ, Wang HD, Song MZ, Xu WP, Yuan YB, Yang YY, Xiao PX. Epigenetic repression of THBD transcription by BRG1 contributes to deep vein thrombosis. Thromb Res. 2022 Nov;219:121-132. doi: 10.1016/j.thromres.2022.09.015. Epub 2022 Sep 19. PMID: 36162255.
In vitro protocol: 1. Gerstenberger BS, Trzupek JD, Tallant C, Fedorov O, Filippakopoulos P, Brennan PE, Fedele V, Martin S, Picaud S, Rogers C, Parikh M, Taylor A, Samas B, O'Mahony A, Berg E, Pallares G, Torrey AD, Treiber DK, Samardjiev IJ, Nasipak BT, Padilla-Benavides T, Wu Q, Imbalzano AN, Nickerson JA, Bunnage ME, Müller S, Knapp S, Owen DR. Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit. J Med Chem. 2016 May 26;59(10):4800-11. doi: 10.1021/acs.jmedchem.6b00012. Epub 2016 May 3. PMID: 27115555; PMCID: PMC5034155. 2. Fedorov O, Castex J, Tallant C, Owen DR, Martin S, Aldeghi M, Monteiro O, Filippakopoulos P, Picaud S, Trzupek JD, Gerstenberger BS, Bountra C, Willmann D, Wells C, Philpott M, Rogers C, Biggin PC, Brennan PE, Bunnage ME, Schüle R, Günther T, Knapp S, Müller S. Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance. Sci Adv. 2015 Nov 13;1(10):e1500723. doi: 10.1126/sciadv.1500723. PMID: 26702435; PMCID: PMC4681344.
In vivo protocol: 1. Li N, Liu H, Xue Y, Xu Z, Miao X, Guo Y, Li Z, Fan Z, Xu Y. Targetable Brg1-CXCL14 axis contributes to alcoholic liver injury by driving neutrophil trafficking. EMBO Mol Med. 2023 Mar 8;15(3):e16592. doi: 10.15252/emmm.202216592. Epub 2023 Feb 1. PMID: 36722664; PMCID: PMC9994483. 2. Wu T, Kong M, Xin XJ, Liu RQ, Wang HD, Song MZ, Xu WP, Yuan YB, Yang YY, Xiao PX. Epigenetic repression of THBD transcription by BRG1 contributes to deep vein thrombosis. Thromb Res. 2022 Nov;219:121-132. doi: 10.1016/j.thromres.2022.09.015. Epub 2022 Sep 19. PMID: 36162255.

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1: Fedorov O, Castex J, Tallant C, Owen DR, Martin S, Aldeghi M, Monteiro O,
Filippakopoulos P, Picaud S, Trzupek JD, Gerstenberger BS, Bountra C, Willmann D,
Wells C, Philpott M, Rogers C, Biggin PC, Brennan PE, Bunnage ME, Schüle R,
Günther T, Knapp S, Müller S. Selective targeting of the BRG/PB1 bromodomains
impairs embryonic and trophoblast stem cell maintenance. Sci Adv. 2015 Nov
13;1(10):e1500723. doi: 10.1126/sciadv.1500723. eCollection 2015 Nov. PubMed
PMID: 26702435; PubMed Central PMCID: PMC4681344.


2: Vangamudi B, Paul TA, Shah PK, Kost-Alimova M, Nottebaum L, Shi X, Zhan Y, Leo
E, Mahadeshwar HS, Protopopov A, Futreal A, Tieu TN, Peoples M, Heffernan TP,
Marszalek JR, Toniatti C, Petrocchi A, Verhelle D, Owen DR, Draetta G, Jones P,
Palmer WS, Sharma S, Andersen JN. The SMARCA2/4 ATPase Domain Surpasses the
Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue
and PFI-3 Inhibitor Studies. Cancer Res. 2015 Sep 15;75(18):3865-78. doi:
10.1158/0008-5472.CAN-14-3798. Epub 2015 Jul 2. PubMed PMID: 26139243; PubMed
Central PMCID: PMC4755107.