Gedatolisib (PF-05212384, PKI-587)
Molecular Weight(MW): 615.73
Gedatolisib (PF-05212384, PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ and mTOR with IC50 of 0.4 nM, 5.4 nM and 1.6 nM in cell-free assays, respectively. Phase 2.
Cited by 7 Publications
2 Customer Reviews
PI3K inhibitors promote apoptosis in checkpoint-defective cell lines. Two checkpoint-functional (A2058, D28) and three defective (HT144, D20, SKMel13) melanoma cell lines growth as tumour spheres as in Figure 4B were either untreated or treated with 5 uM PF-05212384 for 72 h, harvested and immunoblotted for pAkt Ser473.
Pigment Cell Melanoma Res 2014 27(5), 813-21. Gedatolisib (PF-05212384, PKI-587) purchased from Selleck.
Purity & Quality Control
Choose Selective PI3K Inhibitors
|Description||Gedatolisib (PF-05212384, PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ and mTOR with IC50 of 0.4 nM, 5.4 nM and 1.6 nM in cell-free assays, respectively. Phase 2.|
PKI-587 shows potent inhibitory activity against PI3K-α, PI3K-γ and mTOR with IC50 of 0.4 nM, 5.4 nM and 1.6 nM, respectively. Furthermore, PKI-587 also exhibits its potency against the most frequently occurring mutant forms of PI3Kα, notably the H1047R and E545K with IC50 of 0.6 nM and 0.6 nM, respectively.  Correlated with suppression of phosphorylation of PI3K/mTOR signaling pathway proteins, PKI-587 causes tumor cell growth inhibition in MDA-361 and PC3-MM2 cell lines with IC50 of 4 nM and 13.1 nM, respectively. 
|In vivo||In nude mice, PKI-587 treatment at 25 mg/kg iv leads to low plasma clearance (7 (mL/min)/kg), high volume of distribution (7.2 L/kg), and long half-life, (14.4 hours). In the MDA-361 xenograft model, PKI-587 produces potent antitumor efficacy with the minimum efficacious dose (MED) of 3 mg/kg against MDA-361 tumors and maximum tolerated single dose (MTD) of 30 mg/kg. While in the H1975 (non-small-cell lung carcinoma, mutant EGFR [L858R, T790M]) xenograft model, PKI-587 at 25 mg/kg for 7 weeks results in 90% survival of the group treated. |
PI3K and mTOR kinase assay :Enzyme assays are done in fluorescent polarization (FP) format, adapted from the Echelon K-1100 PI3K FP assay kit protocol. Human class I PI3Ks and PI3K-α mutants (E545K and H1047R) are produced in Sf9 or purchased from Upstate Biotech. GST-GRP1 (murine) is produced in Escherichia coli and isolated by GST-Sepharose. Assay buffers are reaction buffer [20 mM HEPES (pH 7.1), 2 mM MgCl2, 0.05% CHAPS, and 0.01% β-mercaptoethanol] and stop/detection buffer [100 mM HEPES (pH 7.5), 4 mM EDTA, 0.05% CHAPS]. FP reaction is run for 30 minutes at room temperature in 20 μL of reaction buffer containing 20 μM phosphatidylinositol 4,5-bisphosphate (PIP2), 25 μM ATP, and <4% DMSO. FP reaction is stopped with 20 μL of stop/detection buffer (10 nM probe and 40 nM GST-GRP), and after 2 hours, data are collected using an Envision plate reader. The routine assays with purified FLAG-TOR (FL and 3.5) are performed in 96-well plates as follows. Enzymes are first diluted in kinase assay buffer (10 mM Hepes (pH 7.4), 50 mM NaCl, 50 mM β-glycerophosphate, 10 mM MnCl2, 0.5 mM DTT, 0.25 μM microcystin LR, and 100 μg/mL BSA). To each well, 12 μL of the diluted enzyme is mixed briefly with 0.5 μL test inhibitor or control vehicle dimethyl sulfoxide (DMSO). The kinase reaction is initiated by adding 12.5 μL kinase assay buffer containing ATP and His6-S6K to give a final reaction volume of 25 μL containing 800 ng/mL FLAG-TOR, 100 μM ATP, and 1.25 μM His6-S6K. The reaction plate is incubated for 2 hours (linear at 1–6 hours) at room temperature with gentle shaking and then terminated by adding 25 μL Stop buffer (20 mM Hepes (pH 7.4), 20 mM EDTA, and 20 mM EGTA).
|In vitro||DMSO||2 mg/mL (3.24 mM)|
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT02438761||Terminated||Drug: PF-05212384||Therapy-related Acute Myeloid Leukemia and Myelodysplastic Syndrome|Acute Myeloid Leukemia in Relapse|de Novo Acute Myeloid Leukemia at Diagnostic||Institut Curie|Fondation ARC|National Cancer Institute France||August 31 2015||Phase 2|
|NCT02069158||Completed||Drug: PF-05212384|Drug: Paclitaxel|Drug: Carboplatin||Breast Cancer|NSCLC|Ovary Cancer|Endometrial Cancer|Small Cell Lung Cancer (SCLC)|Head and Neck (HNSCC)||Cristiana Sessa|Oncology Institute of Southern Switzerland||April 2014||Phase 1|
|NCT01420081||Terminated||Drug: PF-05212384||Endometrial Neoplasms||Pfizer||January 19 2012||Phase 2|
|NCT01347866||Terminated||Drug: PF-05212384|Drug: PD-0325901|Drug: irinotecan||Advanced Cancer||Pfizer||October 2011||Phase 1|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.