| Identification | Back Directory | [Name]
PI-1840 | [CAS]
1401223-22-0 | [Synonyms]
PI-1840
CS-2559
PI 1840;PI1840
N-isopropyl-2-(4-propylphenoxy)-N-((3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)methyl)acetamide
N-(1-methylethyl)-2-(4-propylphenoxy)-N-[[3-(3-pyridinyl)-1,2,4-oxadiazol-5-yl]methyl]-acetamide | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C22H26N4O3 | [MDL Number]
MFCD28142700 | [MOL File]
1401223-22-0.mol | [Molecular Weight]
394.467 |
| Chemical Properties | Back Directory | [Boiling point ]
584.6±60.0 °C(Predicted) | [density ]
1.165±0.06 g/cm3(Predicted) | [storage temp. ]
Desiccate at -20°C | [solubility ]
insoluble in H2O; ≥4.44 mg/mL in EtOH with ultrasonic; ≥70.7 mg/mL in DMSO | [form ]
solid | [pka]
1.57±0.12(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
PI 1840 is a novel rapidly reversible proteasome inhibitor with antitumor activity. | [Biological Activity]
pi-1840 is a potent and selective inhibitor of proteasome with ic50 value of 27 nm for chymotrypsinlike (ct-l) activity [1].the 26s proteasome consists of a 19s regulatory particle (rp) and a 20s core particle. the 26s proteasome have three main catalytic activities: chymotrypsin-like (ct-l), peptidylglutamyl peptide hydrolyzing-like (pgph-l) and trypsin-like (t-l) activities. ct-l activity plays an important role in the degradation of tumor suppressor and apoptotic proteins [1].pi-1840 is a rapidly reversible and non-covalent proteasome ct-l inhibitor. pi-1840 exhibited excellent selectivity for ct-l over pgph-l and t-l activities. in mda-mb-468 human breast cancer cells, pi-1840 inhibited the ct-l activity with ic50 value of 0.37 μm and inhibited cell survival/proliferation [1]. also, pi-1840 exhibited 121-fold selectivity for the constitutive 20 s proteasome over the immunoproteasome with ic50 values of 18 and 2170 nm, respectively. in mda-mb-468 cells, pi-1840 caused the accumulation of ct-l substrates iκb-α, p27 and bax. also, pi-1840 reduced the levels of survivin, p-akt and ser(p)-6 and induced apoptosis through poly(adp-ribose) polymerase cleavage and caspase-3 activation [2].in nude mice bearing human breast tumor, pi-1840 (150 mg/kg/day, i.p, daily) inhibited tumor growth by 85% [2]. | [Enzyme inhibitor]
This potent proteasome inhibitor (FW = 394.38 g/mol) selectively targets its
chymotrypsin-like activity, or CT-L (IC50 = 27 nM), while showing much
weaker action (IC50 values >100 μM) against its Trypsin-Like (T-L) and
peptidylglutamyl peptide hydrolyzing, or PGPH activities. Mass
spectrometry and equilibrium dialysis show no evidence of covalent linkage
of PI-1840 with any proteasomal protein component. In intact cancer cells,
PI-1840 inhibits CT-L activity, inducing the accumulation of proteasome
substrates p27, Bax and IκB-α, thereby inhibiting survival pathways and
viability, and inducing apoptosis. PI=1840 is also >100x more active
against the constitutive proteasome, compared to immunoproteasome. | [target]
CT-L | [storage]
Desiccate at -20°C | [References]
[1]. ozcan s, kazi a, marsilio f, et al. oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors. j med chem, 2013, 56(10): 3783-3805.
[2]. kazi a, ozcan s, tecleab a, et al. discovery of pi-1840, a novel noncovalent and rapidly reversible proteasome inhibitor with anti-tumor activity. j biol chem, 2014, 289(17): 11906-11915. |
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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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