371935-74-9 Usage
Description
PI-103 is a potent cell-permeable pyridinylfuranopyrimidine compound that acts as a dual inhibitor of Class IA phosphatidylinositol 3-kinase (PI3-K) and mammalian target of rapamycin complex 1 (mTORC1). It is a dual-kinase inhibitor with anti-cancer properties, effectively blocking PI3-K/Akt signaling and cell proliferation in various cancer cell lines. PI-103 is also known to enhance tumor radiosensitivity and has shown synergistic effects with other treatments, such as arsenic disulfide, to eradicate cancer stem cells.
Uses
Used in Anticancer Applications:
PI-103 is used as an anticancer agent for its ability to inhibit the growth of various cancer cell lines, including myelogenous leukemia, non-small cell lung cancer, and glioma. It modulates oncological signaling pathways and synergizes with other treatments to enhance chemo-sensitivity and efficacy in resistant cases.
Used in Radiosensitization:
PI-103 is used to enhance tumor radiosensitivity, making it a valuable tool in combination with radiation therapy for cancer treatment.
Used in Drug Resistance:
PI-103 is used to induce autophagy in drug-resistant glioma, potentially overcoming resistance to certain treatments and improving patient outcomes.
Used in Neuroprotection:
PI-103 is used to protect against a-synuclein-induced toxicity in human neurons by inducing macroautophagy, which may have implications for the treatment of neurodegenerative diseases.
Used in Drug Delivery Systems:
While not explicitly mentioned in the provided materials, PI-103's potential applications in drug delivery systems could be explored to improve its delivery, bioavailability, and therapeutic outcomes in various cancer treatments.
Biological Activity
Inhibitor of DNA-PK, PI 3-kinase (p110 α ) and mTOR (IC 50 values are 2, 8, 20, 26, 48, 83, 88, 150, 850, 920, ~ 1000 and 2300 nM for DNA-PK, p110 α , mTORC1, PI3KC2 β , p110 δ , mTORC2, p110 β , p110 γ , ATR, ATM, PI3KC2 α and hsVPS34 respectively). Inhibits growth of human tumor xenografts in mice in vivo .
Biochem/physiol Actions
Cell permeable: yes
References
Knight et al. (2006), A Pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling; Cell, 125 733
Raynaud et al. (2007), Pharmacologic characterization of a potent inhibitor of a class I phosphatidylinositide 3-kinases; Cancer Res., 67 5840
Hong et al. (2011), Arsenic disulfide synergizes with the phosphoinositide 3-kinase inhibitor PI-103 to eradicate acute myeloid leukemia stem cells by inducing differentiation; Carcinogenesis, 32 1550
Zou et al. (2009), A novel dual PI3Kalpha/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells; Int. J. Mol. Med. 24 97
Fan et al. (2010), Akt and autophagy cooperate to promote survival of drug-resistant glioma; Sci. Signal., 3 ra81
Hollerhage et al. (2019), Multiple molecular pathways stimulating macroautophagy protect from alpha-synuclein-induced toxicity in human neurons; Neuropharmacology, 149 13
Check Digit Verification of cas no
The CAS Registry Mumber 371935-74-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,7,1,9,3 and 5 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 371935-74:
(8*3)+(7*7)+(6*1)+(5*9)+(4*3)+(3*5)+(2*7)+(1*4)=169
169 % 10 = 9
So 371935-74-9 is a valid CAS Registry Number.
371935-74-9Relevant articles and documents
Development of a bioavailable boron-containing PI-103 Bioisostere, PI-103BE
Guo, Shanchun,He, Ling,Luo, Lan,Wang, Guangdi,Zhang, Changde,Zhang, Qiang,Zheng, Shilong,Zhong, Qiu
, (2020)
PI-103 (7) is a potent dual phosphatidylinositol 3-kinase (PI3K)/mTOR inhibitor, but its rapid in vivo metabolism hinders its further clinical development. To improve the bioavailability of PI-103, we designed and synthesized a PI-103 bioisostere, PI-103B
