144707-18-6 Usage
Uses
2-D08 has been used as a small ubiquitin-like modifier (SUMO)ylation inhibitor.
Biological Activity
2-d08 (2’,3’,4’-trihydroxyflavone) is a sumoylation inhibitor.protein sumoylation is a dynamic posttranslational modification involved in various biological processes, such as cellular homeostasis and development. sumoylation has been reported to play a key role in cancer, though so far there are few small molecule probes available.
Biochem/physiol Actions
2-D08 is a potent and cell-permeable inhibitor of sumoylation that block the transfer of SUMO (small ubiquitin-like modifier) from the E2 enzyme (Ubc9) thioester conjugate to the substrate.
in vitro
2-d08 was identified as a cell permeable, mechanistically unique inhibitor of protein sumoylation. 2-D08 was found to be able to block sumoylation of topoisomerase i in two different cancer cell lines when co-dosed with camptothecin. in addition, futher analyses indicated that 2-d08 inhibited sumoylation via preventing transfer of small ubiquitin-like modifier (sumo) from the ubc9-sumo thioester to the substrate without affecting sumo-activating enzyme e1 (sae-1/2) or e2 ubc9-sumo thioester formation, a mechanism of action that was unprecedented before [1]. moreover, it was found that 2-d08 at 100 μm could effectively inhibit 10 μm camptothecin induced topoisomerase i sumoylation in breast cancer without affecting overall cellular protein ubiquitinations [2].
references
[1] kim ys, keyser sg, schneekloth js jr. synthesis of 2',3',4'-trihydroxyflavone (2-d08), an inhibitor of protein sumoylation. bioorg med chem lett. 2014 feb 15;24(4):1094-7. [2] kim ys, nagy k, keyser s, schneekloth js jr. an electrophoretic mobility shift assay identifies a mechanistically unique inhibitor of protein sumoylation. chem biol. 2013 apr 18;20(4):604-13.
Check Digit Verification of cas no
The CAS Registry Mumber 144707-18-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,4,7,0 and 7 respectively; the second part has 2 digits, 1 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 144707-18:
(8*1)+(7*4)+(6*4)+(5*7)+(4*0)+(3*7)+(2*1)+(1*8)=126
126 % 10 = 6
So 144707-18-6 is a valid CAS Registry Number.
144707-18-6Relevant articles and documents
Synthesis of 2′,3′,4′-trihydroxyflavone (2-D08), an inhibitor of protein sumoylation
Kim, Yeong Sang,Keyser, Samantha G.L.,Schneekloth Jr., John S.
, p. 1094 - 1097 (2014/03/21)
Protein sumoylation is a dynamic posttranslational modification involved in diverse biological processes during cellular homeostasis and development. Recently sumoylation has been shown to play a critical role in cancer, although to date there are few small molecule probes available to inhibit enzymes involved in the SUMO conjugation process. As part of a program to identify and study inhibitors of sumoylation we recently reported the discovery that 2′,3′,4′-trihydroxyflavone (2-D08) is a cell permeable, mechanistically unique inhibitor of protein sumoylation. The work reported herein describes an efficient synthesis of 2-D08 as well as a structurally related but inactive isomer. We also report an unanticipated Wessely-Moser rearrangement that occurs under vigorous methyl ether deprotection conditions. This rearrangement likely gave rise to 2-D08 during a deprotection step, resulting in 2-D08 appearing as a contaminant in a screening well from a commercial supplier.
