PFI-1 (PF-6405761)

• CAT Number: A000272
• CAS Number: 1403764-72-6
• Molecular Formula: C16H17N3O4S
• Molecular Weight: 347.4
• Purity: ≥95%
• Target: Bromodomain
• Solubility: Soluble in DMSO > 10 mM
• Storage: 3 years -20C powder
• InChI: InChI=1S/C16H17N3O4S/c1-19-10-11-9-12(7-8-13(11)17-16(19)20)18-24(21,22)15-6-4-3-5-14(15)23-2/h3-9,18H,10H2,1-2H3,(H,17,20)
• InChIKey: TXZPMHLMPKIUGK-UHFFFAOYSA-N
• SMILES: O=S(C1=C(OC)C=CC=C1)(NC2=CC=C(NC(N(C)C3)=O)C3=C2)=O

PFI-1 is a potent and highly selective protein interaction Inhibitor, which targets BET bromodomain. PFI-1 that efficiently blocks the interaction of BET BRDs with acetylated histone tails. Co-crystal structures showed that PFI-1 acts as an acetyl-lysine (Kac) mimetic inhibitor efficiently occupying the Kac binding site in BRD4 and BRD2. PFI-1 has antiproliferative effects on leukaemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G1 cell cycle arrest, down-regulation of MYC expression as well as induction of apoptosis and induces differentiation of primary leukaemic blasts.

Reference

1: Picaud S, Da Costa D, Thanasopoulou A, Filippakopoulos P, Fish PV, Philpott M, Fedorov O, Brennan P, Bunnage ME, Owen DR, Bradner JE, Taniere P, O/’Sullivan B, Muller S, Schwaller J, Stankovic T, Knapp S. PFI-1 – A highly Selective Protein Interaction Inhibitor Targeting BET bromodomains. Cancer Res. 2013 Apr 10. [Epub ahead of print] PubMed PMID: 23576556.2: Fish PV, Filippakopoulos P, Bish G, Brennan PE, Bunnage ME, Cook AS, Federov O, Gerstenberger BS, Jones H, Knapp S, Marsden B, Nocka K, Owen DR, Philpott M, Picaud S, Primiano MJ, Ralph MJ, Sciammetta N, Trzupek JD. Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem. 2012 Nov 26;55(22):9831-7. doi: 10.1021/jm3010515. Epub 2012 Nov 8. PubMed PMID: 23095041; PubMed Central PMCID: PMC3506127.3: Moore KN, Tian C, McMeekin DS, Thigpen JT, Randall ME, Gallion HH. Does the progression-free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?: a Gynecologic Oncology Group ancillary data analysis. Cancer. 2010 Dec 1;116(23):5407-14. doi: 10.1002/cncr.25480. Epub 2010 Aug 24. PubMed PMID: 20737572.