Bevasiranib

Structural formula
	(3'-5 ') dT ‑ dT ‑ U ‑ G ‑ G ‑ A ‑ G ‑ U ‑ G ‑ G ‑ U ‑ U ‑ C ‑ C ‑ G ‑ G ‑ U ‑ C ‑ G ‑ U ‑ G ; (5 '‑3') A ‑ C ‑ C ‑ U ‑ C ‑ A ‑ C ‑ C ‑ A ‑ A ‑ G ‑ G ‑ C ‑ C ‑ A ‑ G ‑ C ‑ A ‑ C ‑ dT ‑ dT ; G = guanosine -, U = uridine -, A = adenosine -, C = cytidine - dT = thymidine residues in a nucleic acid double strand (5'-3 ') // (3'-5'): direction
General
Non-proprietary name	Bevasiranib
other names	Bevasiranibum; Cand-5; Duplex of thymidylyl (3 '→ 5') - thymidylyl (3 '→ 5') - uridylyl (3 '→ 5') - guanylyl (3 '→ 5') - guanylyl (3 '→ 5') ) -adenylyl- (3 '→ 5') - guanylyl- (3 '→ 5') - uridylyl- (3 '→ 5') - guanylyl- (3 '→ 5') - guanylyl- (3 '→ 5' ) -uridylyl- (3 '→ 5') - uridylyl- (3 '→ 5') - cytidylyl- (3 '→ 5') - cytidylyl- (3 '→ 5') - guanylyl- (3 '→ 5' ) -guanylyl- (3 '→ 5') - uridylyl- (3 '→ 5') - cytidylyl- (3 '→ 5') - guanylyl- (3 '→ 5') - uridylyl- (3 '→ 5' ) -guanosine and thymidylyl- (3 '→ 5') - thymidylyl- (3 '→ 5') - cytidylyl- (3 '→ 5') - adenylyl- (3 '→ 5') - cytidylyl- (3 '→ 5 ') - guanylyl (3' → 5 ') - adenylyl (3' → 5 ') - cytidylyl (3' → 5 ') - cytidylyl (3' → 5 ') - guanylyl (3' → 5 ') - guanylyl (3' → 5 ') - adenylyl (3' → 5 ') - adenylyl (3' → 5 ') - cytidylyl (3' → 5 ') - cytidylyl (3' → 5 ') - adenylyl (3' → 5 ') - cytidylyl (3' → 5 ') - uridylyl (3' → 5 ') - cytidylyl (3' → 5 ') - cytidylyl (3' → 5 ') - adenosine;
Molecular formula	C 401 H 503 N 153 O 290 P 40 (bevasiranib) ; C 401 H 463 N 153 Na 40 O 290 P 40 (bevasiranib sodium) ;
External identifiers / databases
DrugBank	DB06642
Wikidata	Q851528
properties
Molar mass	13.3 k Da (bevasiranib) ; 14.2 kDa (Bevasiranib Sodium) ;
safety instructions
GHS hazard labeling ; no classification available
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Bevasiranib is a biological agent in the clinical development phase from the group of RNAi therapeutics . Chemically, it is a so-called siRNA and one of the first active ingredients of this group of substances to be tested on patients. Bevasiranib works by silencing the gene for the Vascular Endothelial Growth Factor (VEGF) through RNA interference . It is believed to have the potential to be used as a drug in the treatment of age-related macular degeneration . Bevasiranib was developed by the pharmaceutical company OPKO .

Pharmacological properties

Mechanism of action (pharmacodynamics)

As an siRNA, bevasiranib differs from conventional low molecular weight and proteinaceous drugs. It makes use of the cell's own mechanism of RNA interference and inhibits the activation of the VEGF gene. As a result, less VEGF protein is produced at the administration site. Unlike other VEGF inhibitors, such as bevacizumab and ranibizumab , bevasiranib does not directly block growth factor protein. Bevasiranib therefore has no immediate effect, as VEGF that is already present has to be broken down first.

In animal experiments, bevasiranib inhibits the neovascularization of the retina and choroid membrane, which is responsible for age-related macular degeneration .

Absorption and distribution in the body (pharmacokinetics)

After an intravitreal injection into the vitreous humor of the eye, bevasiranib is distributed in animal experiments to the iris , the sclera and especially the retina. The highest concentration is reached in the target tissues after 24 to 72 hours. The half-life in the eye is between 50 and 80 hours.

history

Bevasiranib was the first siRNA tested in patients in phase III clinical trials . The first phase III trial, called COBALT study ( Co mbining- B evasiranib- A nd orbitals L ucentis- T herapy study) was canceled after it became clear that the study objective can not be achieved. Further phase III clinical trials with other dosage regimens are in preparation.

Individual evidence

^ ^A ^b ^c World Health Organization: International Nonproprietary Names for Pharmaceutical Substances (INN) - Recommended International Nonproprietary Names: List 61 . In: WHO Drug Information . 23, No. 1, 2009.
↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ Empire SJ, Fosnot J, Kuroki A, et al. : Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model . In: Mol. Vis. . 9, May 2003, pp. 210-216. PMID 12789138 .
↑ Dejneka NS, Wan S, Bond OS, Kornbrust DJ, Reich SJ: Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes . In: Mol. Vis. . 14, 2008, pp. 997-1005. PMID 18523657 . PMC 2405815 (free full text).
↑ ClinicalTrials.gov: Safety & Efficacy Study Evaluating the Combination of Bevasiranib & Lucentis Therapy in Wet AMD (COBALT) . Retrieved November 7, 2010.

[INN-1] A ^b ^c World Health Organization: International Nonproprietary Names for Pharmaceutical Substances (INN) - Recommended International Nonproprietary Names: List 61 . In: WHO Drug Information . 23, No. 1, 2009.

[NV-2] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[Reich_SJ_et_al._(2003)-3] Empire SJ, Fosnot J, Kuroki A, et al. : Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model . In: Mol. Vis. . 9, May 2003, pp. 210-216. PMID 12789138 .

[Dejneka_NS_et_al._(2008)-4] Dejneka NS, Wan S, Bond OS, Kornbrust DJ, Reich SJ: Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes . In: Mol. Vis. . 14, 2008, pp. 997-1005. PMID 18523657 . PMC 2405815 (free full text).

[CT_COBALT-5] ClinicalTrials.gov: Safety & Efficacy Study Evaluating the Combination of Bevasiranib & Lucentis Therapy in Wet AMD (COBALT) . Retrieved November 7, 2010.