PCI-33380 is a novel and irreversible Bruton's Tyrosine Kinase (BTK) inhibitor that was designed based on the ibrutinib scaffold in combination with a fluorescent probe, and has been used in both cellular and in vivo studies that demonstrated the connection between the inhibitor binding event and phenotypic readouts of cellular responses due to the inhibition of Btk functions. The right drug dosage for patients has been determined in large part by the use of fluorescent probes in clinical trials.
Physicochemical Properties
| Molecular Formula | C46H52BF2N11O3 |
| Molecular Weight | 855.800 |
| Exact Mass | 855.43 |
| Elemental Analysis | C, 64.56; H, 6.12; B, 1.26; F, 4.44; N, 18.00; O, 5.61 |
| CAS # | 1022899-36-0 |
| Related CAS # | 1022899-36-0 |
| PubChem CID | 168008660 |
| Appearance | Dark-red to brown-red solid powder |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 13 |
| Heavy Atom Count | 63 |
| Complexity | 1750 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | [B-]1(N2C(=CC(=C2C=C3[N+]1=C(C=C3)CCC(=O)NCCN4CCN(CC4)C/C=C/C(=O)N5CCCC(C5)N6C7=NC=NC(=C7C(=N6)C8=CC=C(C=C8)OC9=CC=CC=C9)N)C)C)(F)F |
| InChi Key | YUGFMNZIROEBNV-YRNVUSSQSA-N |
| InChi Code | InChI=1S/C46H52BF2N11O3/c1-32-28-33(2)58-40(32)29-36-15-14-35(59(36)47(58,48)49)16-19-41(61)51-20-23-56-26-24-55(25-27-56)21-7-11-42(62)57-22-6-8-37(30-57)60-46-43(45(50)52-31-53-46)44(54-60)34-12-17-39(18-13-34)63-38-9-4-3-5-10-38/h3-5,7,9-15,17-18,28-29,31,37H,6,8,16,19-27,30H2,1-2H3,(H,51,61)(H2,50,52,53)/b11-7+ |
| Chemical Name | N-[2-[4-[(E)-4-[3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-4-oxobut-2-enyl]piperazin-1-yl]ethyl]-3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)propanamide |
| Synonyms | PCI-33380; PCI 33380; PCI33380; BMS 790052; BMS-790052; BMS790052; EBP 883; EBP-883; EBP883 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | BTK |
| ln Vitro | PCI-33380 bound to Btk could be found using fluorescent gel scanning and denaturing gel electrophoresis[2]. |
| Cell Assay |
Cell Line: Human B cells. Concentration: 2 μM. Incubation Time: 1 h. Result: Found that 10 nM of PCI-32765 was sufficient to fully occupy the active site of Btk in primary B cells in culture by using the fluorescently tagged derivative PCI-33380. |
| References |
[1]. A novel 2,5-diaminopyrimidine-based affinity probe for Bruton's tyrosine kinase. Sci Rep. 2015 Nov 4;5:16136. [2]. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 50 mg/mL (~58.4 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1685 mL | 5.8425 mL | 11.6850 mL | |
| 5 mM | 0.2337 mL | 1.1685 mL | 2.3370 mL | |
| 10 mM | 0.1168 mL | 0.5842 mL | 1.1685 mL |