1808011-22-4 Usage
Biological Activity
epz031686 is the first smyd3 inhibitor.set and mynd domain containing 3 (smyd3), a lysine methyltransferase (kmt) expressed at high levels in a number of different cancer histologies, is reported to be associated with a poor clinical prognosis.
in vitro
epz031686 was the first smyd3 inhibitor found to show double-digit nanomolar cellular activity. in addition, epz031686 displayed noncompetitive inhibition to both sam and mekk2 with a ki = 1.2 and 1.1 nm, respectively. moreover, epz031686 showed less than 30% inhibition against 16 histone methyltransferase targets at a 10 μm [1].
in vivo
male mice i.v. administered a single dose of epz031686 at 1 mg/kg showed a moderate clearance of 27 ml/min/kg, which was in very good agreement with the microsomal data, with a volume of distribution at steady state of 2.3 l/kg, translating to a terminal half-life of 1.7 h. around 20% of the administered dose was excreted unchanged in urine after 24 h, equivalent to a renal clearance of 5.3 ml/min/kg. bioavailability of 48 and 69 was observed at 5 and 50 mg/kg, respectively, resulting in the epz031686 unbound blood concentration remaining above the smyd3 ic50 value for more than 12 h after a 50 mg/kg p.o. administration [1].
references
[1] mitchell lh et al. novel oxindole sulfonamides and sulfamides: epz031686, the first orally bioavailable small molecule smyd3 inhibitor. acs med chem lett. 2015 aug 27;7(2):134-8.
Check Digit Verification of cas no
The CAS Registry Mumber 1808011-22-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,8,0,8,0,1 and 1 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 1808011-22:
(9*1)+(8*8)+(7*0)+(6*8)+(5*0)+(4*1)+(3*1)+(2*2)+(1*2)=134
134 % 10 = 4
So 1808011-22-4 is a valid CAS Registry Number.
1808011-22-4Relevant articles and documents
Novel Oxindole Sulfonamides and Sulfamides: EPZ031686, the First Orally Bioavailable Small Molecule SMYD3 Inhibitor
Mitchell, Lorna H.,Boriack-Sjodin, P. Ann,Smith, Sherri,Thomenius, Michael,Rioux, Nathalie,Munchhof, Michael,Mills, James E.,Klaus, Christine,Totman, Jennifer,Riera, Thomas V.,Raimondi, Alejandra,Jacques, Suzanne L.,West, Kip,Foley, Megan,Waters, Nigel J.,Kuntz, Kevin W.,Wigle, Tim J.,Scott, Margaret Porter,Copeland, Robert A.,Smith, Jesse J.,Chesworth, Richard
, p. 134 - 138 (2016)
SMYD3 has been implicated in a range of cancers; however, until now no potent selective small molecule inhibitors have been available for target validation studies. A novel oxindole series of SMYD3 inhibitors was identified through screening of the Epizyme proprietary histone methyltransferase-biased library. Potency optimization afforded two tool compounds, sulfonamide EPZ031686 and sulfamide EPZ030456, with cellular potency at a level sufficient to probe the in vitro biology of SMYD3 inhibition. EPZ031686 shows good bioavailability following oral dosing in mice making it a suitable tool for potential in vivo target validation studies.
