| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
PFI-1 (PF6405761) is a novel, highly potent and selective BET (bromodomain-containing protein) inhibitor with antineoplastic activity. It inhibits BRD4 with an IC50 of 0.22 μM in cell-free assays. 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. 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.
| ln Vitro |
PFI-1 exhibits antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic proliferation. Exposure of sensitive cell lines with PFI-1 resulted in G1 cell-cycle arrest, downregulation of MYC expression, as well as activation of apoptosis and causes differentiation of primary leukemic blasts. Cells treated to PFI-1 demonstrate considerable downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, giving an additional technique for the selective suppression of this well-established oncology target[1]. PFI-1 interacts to the cyclic AMP response binding protein with Kd of 49 μM. PFI-1 has an EC50 of 1.89 μM for the suppression of IL6 generation from human blood mononuclear cells stimulated by LPS[2]. PFI-1 produces dose-dependent loss of cell viability in T4302 CD133+ cells[3]. PFI-1 inhibits the proliferation of three NET cell lines (Bon-1 generated from a pancreatic NET, and H727 and H720 produced from lung NETs)[4].
|
||
|---|---|---|---|
| ln Vivo |
The rat given PFI-1 (1 mg/kg, iv) has a half-life of one hour, a volume of distribution of one L/kg, and a plasma clearance of eighteen mL/min/kg. When PFI-1 is given orally to rats at a dose of 2 mg/kg, the oral bioavailability is as low as 32%. The mouse given PFI-1 (2 mg/kg, sc) has a half-life of roughly 2 hours, a Tmax of 1 hour, and a Cmax of 58 ng/mL[2].
|
||
| Animal Protocol |
|
||
| References |
[1]. Picaud S, et al. PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains. Cancer Res. 2013 May 21. [Epub ahead of print]
[2]. Fish PV, et al. 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. [3]. Cheng Z, et al. Inhibition of BET bromodomain targets genetically diverse glioblastoma. Clin Cancer Res. 2013 Apr 1;19(7):1748-59. [4]. Kate E Lines, et al. Epigenetic modifiers reduce proliferation of human neuroendocrine tumour cell lines. Endocrine Abstracts (2013) 31 P149 |
| Molecular Formula |
C16H17N3O4S
|
|
|---|---|---|
| Molecular Weight |
347.39
|
|
| CAS # |
1403764-72-6
|
|
| Related CAS # |
|
|
| SMILES |
O=S(C1=CC=CC=C1OC)(NC2=CC3=C(NC(N(C)C3)=O)C=C2)=O
|
|
| InChi Key |
TXZPMHLMPKIUGK-UHFFFAOYSA-N
|
|
| InChi Code |
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)
|
|
| Chemical Name |
2-methoxy-N-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzenesulfonamide
|
|
| Synonyms |
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|---|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8786 mL | 14.3930 mL | 28.7861 mL | |
| 5 mM | 0.5757 mL | 2.8786 mL | 5.7572 mL | |
| 10 mM | 0.2879 mL | 1.4393 mL | 2.8786 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA