 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C26H25CLN4O2 |
| Molecular Weight | 460.955304861069 |
| Exact Mass | 460.166 |
| CAS # | 2930090-28-9 |
| Related CAS # | Pifusertib;1402602-94-1 |
| PubChem CID | 156178303 |
| Appearance | White to yellow solid powder |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 33 |
| Complexity | 669 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | Cl.N[C@@]1(C[C@](O)(C)C1)C1C=CC(C2N=C3C4=CN=CC=C4OCN3C=2C2C=CC=CC=2)=CC=1 |
| InChi Key | JPKYUPVHSPWRNX-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C26H24N4O2.ClH/c1-25(31)14-26(27,15-25)19-9-7-17(8-10-19)22-23(18-5-3-2-4-6-18)30-16-32-21-11-12-28-13-20(21)24(30)29-22;/h2-13,31H,14-16,27H2,1H3;1H |
| Chemical Name | 3-amino-1-methyl-3-[4-(5-phenyl-8-oxa-3,6,12-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-4-yl)phenyl]cyclobutan-1-ol;hydrochloride |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | Akt1 4.8 nM (IC50) Akt2 1.6 nM (IC50) Akt3 44 nM (IC50) |
| ln Vitro | In MM cells with elevated baseline p-Akt, Pifusertib hydrochloride (1 μM; 6 hours) inhibits downstream p-FKHR/FKHRL1 and basal phosphorylation of Akt [1]. In MM cells with high baseline phosphorylation of Akt, Pifusertib hydrochloride (0–10 μM; 72 hours) selectively inhibits Akt and causes cytotoxicity [1]. Pifusertib hydrochloride eliminates the myeloid microenvironment's cytoprotective effects in MM cells and BMSCs that are linked to Akt inhibition. In MM cells, carfilzomib-induced cytotoxicity and fatal ER stress are amplified by pflusertib hydrochloride. Pifusertib hydrochloride (0.5, 1 μM) stimulates autophagy and the endoplasmic reticulum stress response, which are linked to the generation of G0/G1 phase arrest and apoptosis [1]. Pifusertib increases the cytotoxicity induced by bortezomib, which is correlated with increases in the lethal endoplasmic reticulum stress marker CHOP, PARP cleavage, and blockade of p-Akt. These findings suggest that Pifusertib increases the cytotoxicity induced by bortezomib and apoptotic signaling [1]. |
| ln Vivo | In a mouse xenograft model of human multiple myeloma, pifusertib hydrochloride (12–16 mg/kg; oral; once daily, 5 days per week for 21 days) suppresses tumor growth [1]. In vivo MM cytotoxicity mediated by bortezomib is enhanced by Pifusertib hydrochloride [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: MM cell lines Tested Concentrations: 0-10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induced significant growth inhibition in MM cell lines with high baseline p-Akt, but not in cell lines with low baseline p-Akt. Western Blot Analysis[1] Cell Types: MM.1S, MM.1R, H929, and KMS11 cells Tested Concentrations: 1 μM Incubation Duration: 6 hrs (hours) Experimental Results: Blocked basal phosphorylation of Akt and downstream p-FKHR/FKHRL1 in MM cells with high baseline p-Akt, but did not inhibit autophosphorylation of PDK1 which phosphorylates Akt at Thr308. |
| Animal Protocol |
Animal/Disease Models: SCID (severe combined immunodeficient) mouse (xenograft models bearing MM.1S cells)[1] Doses: 12, 16 mg/kg Route of Administration: Po; daily for 5 days a week, 21 days Experimental Results: Dramatically diminished MM.1S tumor growth versus vehicle control. |
| References |
[1]. Selective and potent Akt inhibition triggers anti-myeloma activities and enhances fatal endoplasmic reticulum stress induced by proteasome inhibition. Cancer Res. 2014;74(16):4458-4469. |
Solubility Data
| Solubility (In Vitro) | DMSO : 62.5 mg/mL (135.59 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.51 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 20.8 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: ≥ 2.08 mg/mL (4.51 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 20.8 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1694 mL | 10.8469 mL | 21.6939 mL | |
| 5 mM | 0.4339 mL | 2.1694 mL | 4.3388 mL | |
| 10 mM | 0.2169 mL | 1.0847 mL | 2.1694 mL |