BORRELIDIN Chemical Properties

Melting point:

143-145℃

Boiling point:

584.45°C (rough estimate)

Density 

1.1362 (rough estimate)

refractive index 

1.6290 (estimate)

storage temp. 

−20°C

solubility 

DMSO: 1 mg/mL

form 

White to off-white powder.

pka

4.56±0.40(Predicted)

color 

Off-white

biological source

Streptomyces parvulus

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.

Safety Information

Safety Statements 

24/25

WGK Germany 

3

RTECS 

ED8750000

HS Code 

29419090

MSDS

• Language:English Provider:SigmaAldrich

BORRELIDIN Usage And Synthesis

Description

Borrelidin (7184-60-3) ia a novel macrolide which inhibits bacterial and eukaryotic threonyl-tRNA synthetase.1 Displays potent anti-angiogenic activity (IC50=0.8 nM) and induces the collapse of newly formed capillary tubules.2 Modulates alternative splicing of VEGF in favor of anti-angiogenic isoforms.3 Induces apoptosis in ALL cell lines.4 Induces unfolded protein response in oral cancer cells.5 Cell permeable.

Uses

Borrelidin is an unusual nitrile-containing metabolite isolated from Streptomyces. Originally discovered as active against Borrelia species, borrelidin has since found a role as a selective inhibitor of bacterial and eukaryal threonyl-tRNA synthetase. More recent research has found that borrelidin is a very potent angiogenesis inhibitor and induces apoptosis of the capillary tube-forming cells. Borrelidin is an important lead for antimalarial discovery, displaying activity against drug-resistant Plasmodia.

Uses

Borrelidin is a secondary metabolite produced by Streptomyces and other bacteria. It displays potent antiangiogenic activity, preventing tube formation in rat aorta explants (IC50 = 0.8 nM) and inducing apoptosis in endothelial cells. Borrelidin also alters the splicing of VEGF mRNA, producing an antiangiogenic isoform of the growth factor. It has long been known as a powerful inhibitor of both eukaryotic and bacterial threonyl tRNA synthetase. Borrelidin is also an effective anti-malarial drug, as it kills P. falciparum with an IC50 value of 1.8 nM. At higher doses, it inhibits cyclin-dependent kinase in yeast (IC50 = 24 μM), resulting in growth arrest in the G1 phase.

Definition

ChEBI: A macrolide that is isolated from several Streptomyces species and displays antibiotic, antineoplastic and antimalarial properties.

General Description

Chemical structure: macrolide

Biochem/physiol Actions

Borrelidin is a potent angiogenesis inhibitor that induces apoptosis in capillary tube-forming cells. Also displays antimalarial activity against drug-resistant Plasmodia. Antimicrobial and selective threonyl t-RNA synthetase inhibitor.

storage

+4°C

References

[1] BENFANG RUAN. A unique hydrophobic cluster near the active site contributes to differences in borrelidin inhibition among threonyl-tRNA synthetases.[J]. The Journal of Biological Chemistry, 2005, 280 1: 571-577. DOI:10.1074/jbc.m411039200
[2] TAKANORI KAWAMURA. Anti-angiogenesis effects of borrelidin are mediated through distinct pathways: threonyl-tRNA synthetase and caspases are independently involved in suppression of proliferation and induction of apoptosis in endothelial cells.[J]. Journal of Antibiotics, 2003, 56 8: 709-715. DOI:10.7164/antibiotics.56.709
[3] WOOLARD J, VOUSDEN W, MOSS S J, et al. Borrelidin modulates the alternative splicing of VEGF in favour of anti-angiogenic isoforms†[J]. Chemical Science, 2010, 2: 273-278. DOI:10.1039/c0sc00297f
[4] DARYA HABIBI. Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthetase, is a potent inducer of apoptosis in acute lymphoblastic leukemia.[J]. Investigational New Drugs, 2012, 30 4: 1361-1370. DOI:10.1007/s10637-011-9700-y
[5] ALPA SIDHU. Borrelidin Induces the Unfolded Protein Response in Oral Cancer Cells and Chop-Dependent Apoptosis[J]. ACS Medicinal Chemistry Letters, 2015, 6 11: 1122-1127. DOI:10.1021/acsmedchemlett.5b00133

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