144707-18-6

Basic information

• Product Name: 2-D08
• Synonyms: 2-D08
• CAS NO: 144707-18-6
• Molecular Formula: C₁₅H₁₀O₅
• Molecular Weight: 270.2369
• Product Categories: API
• Mol File: 144707-18-6.mol

Chemical Properties

• Boiling Point: 517.9±50.0 °C(Predicted)
• Appearance: /
• Density: 1.548±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: ≥74.6 mg/mL in DMSO; ≥1.76 mg/mL in EtOH with gentle warming and ultrasonic; insoluble in H2O
• PKA: 7.45±0.40(Predicted)
• CAS DataBase Reference: 2-D08(CAS DataBase Reference)
• NIST Chemistry Reference: 2-D08(144707-18-6)
• EPA Substance Registry System: 2-D08(144707-18-6)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 144707-18-6(Hazardous Substances Data)

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. this compound 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.

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Relevant articles and documents

Synthesis of 2′,3′,4′-trihydroxyflavone (2-D08), an inhibitor of protein sumoylation

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.