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MedKoo Cat#: 407286 | Name: PFI-2 hydrochloride
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Description:

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

PFI-2 is a potent inhibitor of SETD7 with IC50 2 nM and 1000-fold selectivity over other methyltransferases and other non-epigenetic targets. PFI-2 has been shown to bind to SETD7 by ITC (Kd=18nM) and biotinylated PFI-2 interacts with SETD7 in pull-down studies. Its enantiomer (S)-PFI-2 is 500-fold less active making it an excellent negative control. Treatment of low-density MEFs with (R)-PFI-2 resulted in higher nuclear YAP levels indicating an effect on the Hippo pathway.

Chemical Structure

PFI-2 hydrochloride
PFI-2 hydrochloride
CAS#1627607-87-7 (HCl)

Theoretical Analysis

MedKoo Cat#: 407286

Name: PFI-2 hydrochloride

CAS#: 1627607-87-7 (HCl)

Chemical Formula: C23H26ClF4N3O3S

Exact Mass: 499.1553

Molecular Weight: 535.98

Elemental Analysis: C, 51.54; H, 4.89; Cl, 6.61; F, 14.18; N, 7.84; O, 8.95; S, 5.98

Price and Availability

Size Price Availability Quantity
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
500mg USD 2,650.00 2 Weeks
1g USD 4,650.00 2 Weeks
2g USD 6,450.00 2 Weeks
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Related CAS #
1627607-87-7 (HCl) 1627676-59-8 (free base) 1627676-60-1 (S-isomer free base) 1627607-88-8 (S-isomer HCl)
Synonym
PFI-2; PFI2; PFI 2; (R)-PFI-2; (R)-PFI-2 hydrochloride. PFI-2 hydrochloride
IUPAC/Chemical Name
(R)-8-fluoro-N-(1-oxo-1-(pyrrolidin-1-yl)-3-(3-(trifluoromethyl)phenyl)propan-2-yl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide hydrochloride
InChi Key
ZADKZNVAJGEFLC-ZMBIFBSDSA-N
InChi Code
InChI=1S/C23H25F4N3O3S.ClH/c24-20-13-18(12-16-6-7-28-14-19(16)20)34(32,33)29-21(22(31)30-8-1-2-9-30)11-15-4-3-5-17(10-15)23(25,26)27;/h3-5,10,12-13,21,28-29H,1-2,6-9,11,14H2;1H/t21-;/m1./s1
SMILES Code
O=S(C1=CC2=C(CNCC2)C(F)=C1)(N[C@H](CC3=CC=CC(C(F)(F)F)=C3)C(N4CCCC4)=O)=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, 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
Related CAS# 1627607-87-7 (PFI-2 HCl) 1627607-87-7 (PFI-2 free base)
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PFI-2 ((R)-PFI-2 hydrochloride) hydrochloride is a potent and selective SET domain containing lysine methyltransferase 7 (SETD7) inhibitor.
In vitro activity:
Chemoproteomics experiments using a biotinylated derivative of (R)-PFI-2 demonstrated dose-dependent competition for binding to endogenous SETD7 in MCF7 cells pretreated with (R)-PFI-2. In murine embryonic fibroblasts, (R)-PFI-2 treatment phenocopied the effects of Setd7 deficiency on Hippo pathway signaling, via modulation of the transcriptional coactivator Yes-associated protein (YAP) and regulation of YAP target genes. Reference: Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12853-8. https://pubmed.ncbi.nlm.nih.gov/25136132/
In vivo activity:
In addition, SETD7 regulated H3K4me1 level and expression of inflammatory mediators both in CCI rats and in the HAPI rat microglia cell line. Accordingly, PFI-2, a specific inhibitor of SETD7 monomethylation activity, suppressed the lipopolysaccharides-induced amoeboid morphology of primary microglia and the expression of inflammatory genes, Ccl2, Il-6 and Il-1β. Moreover, intrathecal administration of PFI-2 alleviated CCI-induced neuropathic pain. However, this effect was observed in male but not in female rats. Reference: Brain Behav Immun. 2019 Nov;82:382-395. https://pubmed.ncbi.nlm.nih.gov/31505256/
Solvent mg/mL mM comments
Solubility
DMF 5.0 9.33
DMF:PBS (pH 7.2) (1:1) 0.5 0.93
DMSO 46.7 87.04
Ethanol 0.5 0.93
Water 5.6 10.37
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 535.98 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. Niu Y, Shi D, Li L, Guo J, Liu H, Yao X. Revealing inhibition difference between PFI-2 enantiomers against SETD7 by molecular dynamics simulations, binding free energy calculations and unbinding pathway analysis. Sci Rep. 2017 Apr 18;7:46547. doi: 10.1038/srep46547. PMID: 28417976; PMCID: PMC5394549. 2. Barsyte-Lovejoy D, Li F, Oudhoff MJ, Tatlock JH, Dong A, Zeng H, Wu H, Freeman SA, Schapira M, Senisterra GA, Kuznetsova E, Marcellus R, Allali-Hassani A, Kennedy S, Lambert JP, Couzens AL, Aman A, Gingras AC, Al-Awar R, Fish PV, Gerstenberger BS, Roberts L, Benn CL, Grimley RL, Braam MJ, Rossi FM, Sudol M, Brown PJ, Bunnage ME, Owen DR, Zaph C, Vedadi M, Arrowsmith CH. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12853-8. doi: 10.1073/pnas.1407358111. Epub 2014 Aug 18. PMID: 25136132; PMCID: PMC4156762. 3. Shen Y, Ding Z, Ma S, Ding Z, Zhang Y, Zou Y, Xu F, Yang X, Schäfer MKE, Guo Q, Huang C. SETD7 mediates spinal microgliosis and neuropathic pain in a rat model of peripheral nerve injury. Brain Behav Immun. 2019 Nov;82:382-395. doi: 10.1016/j.bbi.2019.09.007. Epub 2019 Sep 7. PMID: 31505256.
In vitro protocol:
1. Niu Y, Shi D, Li L, Guo J, Liu H, Yao X. Revealing inhibition difference between PFI-2 enantiomers against SETD7 by molecular dynamics simulations, binding free energy calculations and unbinding pathway analysis. Sci Rep. 2017 Apr 18;7:46547. doi: 10.1038/srep46547. PMID: 28417976; PMCID: PMC5394549. 2. Barsyte-Lovejoy D, Li F, Oudhoff MJ, Tatlock JH, Dong A, Zeng H, Wu H, Freeman SA, Schapira M, Senisterra GA, Kuznetsova E, Marcellus R, Allali-Hassani A, Kennedy S, Lambert JP, Couzens AL, Aman A, Gingras AC, Al-Awar R, Fish PV, Gerstenberger BS, Roberts L, Benn CL, Grimley RL, Braam MJ, Rossi FM, Sudol M, Brown PJ, Bunnage ME, Owen DR, Zaph C, Vedadi M, Arrowsmith CH. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12853-8. doi: 10.1073/pnas.1407358111. Epub 2014 Aug 18. PMID: 25136132; PMCID: PMC4156762.
In vivo protocol:
1. Shen Y, Ding Z, Ma S, Ding Z, Zhang Y, Zou Y, Xu F, Yang X, Schäfer MKE, Guo Q, Huang C. SETD7 mediates spinal microgliosis and neuropathic pain in a rat model of peripheral nerve injury. Brain Behav Immun. 2019 Nov;82:382-395. doi: 10.1016/j.bbi.2019.09.007. Epub 2019 Sep 7. PMID: 31505256.
1: Maxwell S, Okabe J, Kaipananickal H, Rodriguez H, Khurana I, Al-Hasani K, Chow BSM, Pitsillou E, Karagiannis TC, Jandeleit-Dahm K, Ma RCW, Huang Y, Chan JCN, Cooper ME, El-Osta A. Set7 Methyltransferase and Phenotypic Switch in Diabetic Glomerular Endothelial Cells. J Am Soc Nephrol. 2024 Jun 1;35(6):733-748. doi: 10.1681/ASN.0000000000000345. Epub 2024 Apr 17. PMID: 38630537; PMCID: PMC11164123. 2: Liu N, Babazono A, Jamal A, Yoshida S, Yamao R, Ishihara R, Matsuda S, Li Y. Impact of fee-revision policy for gastrostomy on its implementation among older adults with dementia in Japan. Public Health. 2024 Feb;227:63-69. doi: 10.1016/j.puhe.2023.11.032. Epub 2023 Dec 20. PMID: 38118244. 3: Xu R, Liu X, Zhang Y, Wang K, Chen Z, Zheng J, Zhang T, Tong P, Qian Y, Yang W. Activating transcriptional coactivator with PDZ-binding motif by (R)-PFI-2 attenuates osteoclastogenesis and prevents ovariectomized-induced osteoporosis. Biochem Pharmacol. 2024 Jan;219:115964. doi: 10.1016/j.bcp.2023.115964. Epub 2023 Dec 2. PMID: 38049011. 4: Porzberg MRB, Lenstra DC, Damen E, Blaauw RH, Rutjes FPJT, Wegert A, Mecinović J. (R)-PFI-2 Analogues as Substrates and Inhibitors of Histone Lysine Methyltransferase SETD7. ChemMedChem. 2023 Dec 1;18(23):e202300457. doi: 10.1002/cmdc.202300457. Epub 2023 Nov 10. PMID: 37872124. 5: Monteiro FL, Góis A, Direito I, Melo T, Neves B, Alves MI, Batista I, Domingues MDR, Helguero LA. Inhibiting SETD7 methyl-transferase activity impairs differentiation, lipid metabolism and lactogenesis in mammary epithelial cells. FEBS Lett. 2023 Nov;597(21):2656-2671. doi: 10.1002/1873-3468.14737. Epub 2023 Oct 3. PMID: 37723127. 6: Pellecchia A, Kritikos M, Guralnik J, Ahuvia I, Santiago-Michels S, Carr M, Kotov R, Bromet EJ, Clouston SAP, Luft BJ. Physical Functional Impairment and the Risk of Incident Mild Cognitive Impairment in an Observational Study of World Trade Center Responders. Neurol Clin Pract. 2022 Dec;12(6):e162-e171. doi: 10.1212/CPJ.0000000000200089. PMID: 36540142; PMCID: PMC9757114. 7: Chung YL, Laiman V, Tsao PN, Chen CM, Heriyanto DS, Chung KF, Chuang KJ, Chuang HC. Diesel exhaust particles inhibit lung branching morphogenesis via the YAP/TAZ pathway. Sci Total Environ. 2023 Feb 25;861:160682. doi: 10.1016/j.scitotenv.2022.160682. Epub 2022 Dec 5. PMID: 36481141. 8: Lyu H, Zhou X, Qian Y, Liu X, Gopinathan G, Pandya M, Qin C, Luan X, Diekwisch TGH. Long-acting PFI-2 small molecule release and multilayer scaffold design achieve extensive new formation of complex periodontal tissues with unprecedented fidelity. Biomaterials. 2022 Nov;290:121819. doi: 10.1016/j.biomaterials.2022.121819. Epub 2022 Sep 22. PMID: 36209579. 9: Li J, Chen C, Zhou H, Zhai J, Zhao H, Li L. Anatomic Risk Factors for Osteochondral Fracture of Acute First-Time Patellar Dislocation in Adolescents: A Retrospective Magnetic Resonance Imaging Study. Evid Based Complement Alternat Med. 2022 Aug 8;2022:6723326. doi: 10.1155/2022/6723326. Retraction in: Evid Based Complement Alternat Med. 2023 Jul 19;2023:9786026. doi: 10.1155/2023/9786026. PMID: 35979012; PMCID: PMC9377871. 10: Ambrosini S, Montecucco F, Kolijn D, Pedicino D, Akhmedov A, Mohammed SA, Herwig M, Gorica E, Szabó PL, Weber L, Russo G, Vinci R, Matter CM, Liuzzo G, Brown PJ, Rossi FMV, Camici GG, Sciarretta S, Beltrami AP, Crea F, Podesser B, Lüscher TF, Kiss A, Ruschitzka F, Hamdani N, Costantino S, Paneni F. Methylation of the Hippo effector YAP by the methyltransferase SETD7 drives myocardial ischaemic injury: a translational study. Cardiovasc Res. 2023 Jan 18;118(17):3374-3385. doi: 10.1093/cvr/cvac102. PMID: 35709329. 11: Zhang H, Bai F, Song H, Yang J, Wang X, Ye Q, Zhou Y. Cumulative effect of risk and protective factors on unintentional injury for Chinese rural children: a nested case-control study. BMC Public Health. 2021 Sep 23;21(1):1730. doi: 10.1186/s12889-021-11769-7. PMID: 34556060; PMCID: PMC8461983. 12: Daks A, Mamontova V, Fedorova O, Petukhov A, Shuvalov O, Parfenyev S, Netsvetay S, Venina A, Kizenko A, Imyanitov E, Barlev N. Set7/9 controls proliferation and genotoxic drug resistance of NSCLC cells. Biochem Biophys Res Commun. 2021 Oct 1;572:41-48. doi: 10.1016/j.bbrc.2021.07.086. Epub 2021 Jul 31. PMID: 34343833. 13: Liu B, Nie J, Liang H, Liang Z, Huang J, Yu W, Wen S. Pharmacological inhibition of SETD7 by PFI-2 attenuates renal fibrosis following folic acid and obstruction injury. Eur J Pharmacol. 2021 Jun 15;901:174097. doi: 10.1016/j.ejphar.2021.174097. Epub 2021 Apr 19. PMID: 33848540. 14: Hallaj T, Amjadi M, Qiu X, Susumu K, Medintz IL, Hildebrandt N. Terbium-to- quantum dot Förster resonance energy transfer for homogeneous and sensitive detection of histone methyltransferase activity. Nanoscale. 2020 Jul 2;12(25):13719-13730. doi: 10.1039/d0nr03383a. PMID: 32573632. 15: Dong Y, Lau PWC, Dong B, Zou Z, Yang Y, Wen B, Ma Y, Hu P, Song Y, Ma J, Sawyer SM, Patton GC. Trends in physical fitness, growth, and nutritional status of Chinese children and adolescents: a retrospective analysis of 1·5 million students from six successive national surveys between 1985 and 2014. Lancet Child Adolesc Health. 2019 Dec;3(12):871-880. doi: 10.1016/S2352-4642(19)30302-5. Epub 2019 Sep 30. PMID: 31582349. 16: Shen Y, Ding Z, Ma S, Ding Z, Zhang Y, Zou Y, Xu F, Yang X, Schäfer MKE, Guo Q, Huang C. SETD7 mediates spinal microgliosis and neuropathic pain in a rat model of peripheral nerve injury. Brain Behav Immun. 2019 Nov;82:382-395. doi: 10.1016/j.bbi.2019.09.007. Epub 2019 Sep 7. PMID: 31505256. 17: Thijssen M, Janssen L, le Noble J, Foudraine N. Facing SpO2 and SaO2 discrepancies in ICU patients: is the perfusion index helpful? J Clin Monit Comput. 2020 Aug;34(4):693-698. doi: 10.1007/s10877-019-00371-3. Epub 2019 Aug 7. PMID: 31392655; PMCID: PMC7366881. 18: Tang B, Li B, Li B, Qin J, Zhao J, Xu J, Qiu Y, Wu Z, Fang M. Insights into the stereoselectivity of human SETD7 methyltransferase. RSC Adv. 2019 Mar 21;9(16):9218-9227. doi: 10.1039/c9ra00190e. PMID: 35517649; PMCID: PMC9062083. 19: Hamidi T, Singh AK, Veland N, Vemulapalli V, Chen J, Hardikar S, Bao J, Fry CJ, Yang V, Lee KA, Guo A, Arrowsmith CH, Bedford MT, Chen T. Identification of Rpl29 as a major substrate of the lysine methyltransferase Set7/9. J Biol Chem. 2018 Aug 17;293(33):12770-12780. doi: 10.1074/jbc.RA118.002890. Epub 2018 Jun 29. PMID: 29959229; PMCID: PMC6102145. 20: Lenstra DC, Damen E, Leenders RGG, Blaauw RH, Rutjes FPJT, Wegert A, Mecinović J. Structure-Activity Relationship Studies on (R)-PFI-2 Analogues as Inhibitors of Histone Lysine Methyltransferase SETD7. ChemMedChem. 2018 Jul 18;13(14):1405-1413. doi: 10.1002/cmdc.201800242. Epub 2018 Jun 25. PMID: 29869845.