| Identification | Back Directory | [Name]
PI-103 (Hydrochloride) | [CAS]
371935-79-4 | [Synonyms]
PI-103 HCl
PI103 Free base
PI-103, Hydrochloride Salt, >99%
PI 103 HYDROCHLORIDE;PI103 HYDROCHLORIDE
3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol,hydrochloride
3-[4-(4-Morpholinyl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol monohydrochloride | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C19H17ClN4O3 | [MOL File]
371935-79-4.mol | [Molecular Weight]
384.816 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in H2O; insoluble in EtOH; ≥19.25 mg/mL in DMSO | [form ]
solid | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
PI-103 Hydrochloride is a dual PI3K and mTOR inhibitor with IC50s of 8 nM, 88 nM, 48 nM, 150 nM, 20 nM, and 83 nM for p110α, p110β, p110δ, p110γ, mTORC1, and mTORC2. PI-103 Hydrochloride also inhibits DNA-PK with an IC50 of 2 nM. PI-103 Hydrochloride induces autophagy[1][2][3][4]. | [Biological Activity]
pi-103 is a dual inhibitor of pi3k/akt and mtor with ic50 value of 0.002 μm , 0.003μm, 0.003μm, 0.015μm, 0.030μm for p110α, p110β, p110γ, p110 and mtor, respectively [1].pi3k/akt/mtor pathway is an intracellular signaling pathway and plays an important role in regulating cell cycle. it has been shown that pi3k/akt/mtor pathway is directly related to cellular quiescence, proliferation, cancer, and longevity. and many studies have shown that activation of the pi3k/akt signaling pathway is correlated with poor prognosis in a variety of cancers which demonstrated that inhibition of the pathway may be regarded as a promising therapy [2, 3].pi-103 is a selective pi3k/akt and mtorc1 inhibitor. when tested with leukemic cell lines (molm14, oci-aml3 and mv4-11) with activation of pi3k/akt, mtorc1 and erk/mapk signaling pathways, pi-103 blocked cells proliferation via inhibiting pi3k/akt and mtorc1 activity in a concentration of 1μm [4]. in hcc cell line--huh7 cells, treated pi-103 alone or combined with sorafenib inhibited cells proliferation in a dose-dependent manner through inhibition of pi3k/akt and mtorc1 pathways [5]. when tested with u87mg glioblastoma cells, pi-103 treatment in 30 nm/l showed significant inhibition of pi3k/akt and mtorc1 phosphorylation [1]. in neuroblastoma cell lines sk-n-be (2), imr-32 with amplified mycn, pi-103 inhibited cell growth in a time- and concentration-dependent manner via inhibiting pi3k/akt and mtorc1 activity [3].in sk-n-be (2) with mycn-mutant xenografted nude mice model, treated pi-103 intraperitoneally (10 mg/kg) markedly reduced the tumor volume index and tumor weight via inhibiting pi3k/ mtor pathways [1]. | [in vivo]
PI-103 shows therapeutic activity against a range of human tumor xenografts, exhibiting inhibition of angiogenesis, invasion, and metastasis, as well as direct antiproliferative effects[1]. PI-103 induces immunosuppression promoting in vivo tumor growth and inhibiting apoptosis. Tumors from PI-103-treated mice shows higher levels of cyclin D1 and more proliferating cells[3]. | [IC 50]
p110α: 2 nM (IC50); p110β: 3 nM (IC50); p110δ: 3 nM (IC50); p110γ: 15 nM (IC50); mTORC1: 20 nM (IC50); mTORC2: 83 nM (IC50); DNA-PK: 23 nM (IC50) | [storage]
Store at -20°C | [References]
[1]. raynaud, f.i., et al., biological properties of potent inhibitors of class i phosphatidylinositide 3-kinases: from pi-103 through pi-540, pi-620 to the oral agent gdc-0941. mol cancer ther, 2009. 8(7): p. 1725-38.
[2]. hambright, h.g., et al., inhibition of pi3k/akt/mtor axis disrupts oxidative stress-mediated survival of melanoma cells. oncotarget, 2015.
[3]. segerstrom, l., et al., effects of small molecule inhibitors of pi3k/akt/mtor signaling on neuroblastoma growth in vitro and in vivo. int j cancer, 2011. 129(12): p. 2958-65.
[4]. park, s., et al., pi-103, a dual inhibitor of class ia phosphatidylinositide 3-kinase and mtor, has antileukemic activity in aml. leukemia, 2008. 22(9): p. 1698-706.
[5]. gedaly, r., et al., pi-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking ras/raf/mapk and pi3k/akt/mtor pathways. anticancer res, 2010. 30(12): p. 4951-8. |
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| Company Name: |
SPIRO PHARMA
|
| Tel: |
|
| Website: |
www.spiropharma.com.cn |
| Company Name: |
BOC Sciences
|
| Tel: |
16314854226 |
| Website: |
www.bocsci.com |
|