Synonym
PF-04979064; PF 04979064; PF04979064.
IUPAC/Chemical Name
2H-Imidazo(4,5-C)(1,5)naphthyridin-2-one, 1,3-dihydro-1-(1-((2S)-2-hydroxy-1-oxopropyl)-4-piperidinyl)-3-methyl-8-(6-methyl-3-pyridinyl)-
InChi Key
GACQNUHFDBEIQH-HNNXBMFYSA-N
InChi Code
InChI=1S/C24H26N6O3/c1-14-4-5-16(12-25-14)18-6-7-19-21(27-18)22-20(13-26-19)28(3)24(33)30(22)17-8-10-29(11-9-17)23(32)15(2)31/h4-7,12-13,15,17,31H,8-11H2,1-3H3/t15-/m0/s1
SMILES Code
O=C(N1C2CCN(C([C@@H](O)C)=O)CC2)N(C)C3=C1C4=NC(C5=CC=C(C)N=C5)=CC=C4N=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PF-04979064 is a potent and selective PI3K/mTOR dual kinase inhibitor with Kis of 0.13 nM and 1.42 nM for PI3Kα and mTOR
In vitro activity:
Integration of structure-based drug design and physical properties-based optimization yielded a potent and selective PI3K/mTOR dual kinase inhibitor PF-04979064. This manuscript discusses the lead optimization for the tricyclic series, which both improved the in vitro potency and addressed a number of ADMET issues including high metabolic clearance mediated by both P450 and aldehyde oxidase (AO), poor permeability, and poor solubility.
Reference: ACS Med Chem Lett. 2012 Nov 7;4(1):91-7. https://pubmed.ncbi.nlm.nih.gov/24900568/
In vivo activity:
Male C57BL/6 mice were randomly divided into sham, model, and PI3K inhibitor groups. Mice were exposed to PM2.5 for 4 weeks to establish an in vivo COPD model. In mice with COPD induced by PM2.5, the PI3K inhibitor PF-04979064 suppressed protein expression of PI3K, p-AKT, and p-mTOR to increase apoptosis of alveolar epithelial cells and reduce autophagy.
Reference: J Int Med Res. 2020 Jul;48(7):300060520927919. https://pubmed.ncbi.nlm.nih.gov/32715876/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
10.0 |
22.40 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
446.51
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Cheng H, Li C, Bailey S, Baxi SM, Goulet L, Guo L, Hoffman J, Jiang Y, Johnson TO, Johnson TW, Knighton DR, Li J, Liu KK, Liu Z, Marx MA, Walls M, Wells PA, Yin MJ, Zhu J, Zientek M. Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. ACS Med Chem Lett. 2012 Nov 7;4(1):91-7. doi: 10.1021/ml300309h. PMID: 24900568; PMCID: PMC4027523.
2. Zhang F, Ma H, Wang ZL, Li WH, Liu H, Zhao YX. The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter. J Int Med Res. 2020 Jul;48(7):300060520927919. doi: 10.1177/0300060520927919. PMID: 32715876; PMCID: PMC7385846.
In vitro protocol:
1. Cheng H, Li C, Bailey S, Baxi SM, Goulet L, Guo L, Hoffman J, Jiang Y, Johnson TO, Johnson TW, Knighton DR, Li J, Liu KK, Liu Z, Marx MA, Walls M, Wells PA, Yin MJ, Zhu J, Zientek M. Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. ACS Med Chem Lett. 2012 Nov 7;4(1):91-7. doi: 10.1021/ml300309h. PMID: 24900568; PMCID: PMC4027523.
In vivo protocol:
1. Zhang F, Ma H, Wang ZL, Li WH, Liu H, Zhao YX. The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter. J Int Med Res. 2020 Jul;48(7):300060520927919. doi: 10.1177/0300060520927919. PMID: 32715876; PMCID: PMC7385846.
1: Zhong Z, Wang T, Zang R, Zang Y, Feng Y, Yan S, Geng C, Zhu N, Wang Q. Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU. Biomed Pharmacother. 2023 Dec 29;170:116086. doi: 10.1016/j.biopha.2023.116086. Epub ahead of print. PMID: 38159377.
2: Zhang F, Ma H, Wang ZL, Li WH, Liu H, Zhao YX. The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter. J Int Med Res. 2020 Jul;48(7):300060520927919. doi: 10.1177/0300060520927919. PMID: 32715876; PMCID: PMC7385846.
3: Cheng H, Li C, Bailey S, Baxi SM, Goulet L, Guo L, Hoffman J, Jiang Y, Johnson TO, Johnson TW, Knighton DR, Li J, Liu KK, Liu Z, Marx MA, Walls M, Wells PA, Yin MJ, Zhu J, Zientek M. Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. ACS Med Chem Lett. 2012 Nov 7;4(1):91-7. doi: 10.1021/ml300309h. PMID: 24900568; PMCID: PMC4027523.
