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| PI-1840 Basic information |
| Product Name: | PI-1840 | | Synonyms: | PI-1840;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;CS-2559;PI 1840;PI1840 | | CAS: | 1401223-22-0 | | MF: | C22H26N4O3 | | MW: | 394.47 | | EINECS: | 604-604-1 | | Product Categories: | Inhibitors | | Mol File: | 1401223-22-0.mol |
| PI-1840 Chemical Properties |
| solubility | insoluble in H2O; ≥4.44 mg/mL in EtOH with ultrasonic; ≥70.7 mg/mL in DMSO | | form | solid |
| PI-1840 Usage And Synthesis |
| 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. | | 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. |
| PI-1840 Preparation Products And Raw materials |
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