DT-Web

DB01270 - Ranibizumab


Identification
Name Ranibizumab
Accession Number DB01270
Type biotech
Description Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). Ranibizumab has a molecular weight of approximately 48 kilodaltons and is produced by an E. coli expression system in a nutrient medium containing the antibiotic tetracycline (tetracycline is not detectable in the final product). Ranibizumab is marketed under the name Lucentis(R). It is indicated for the treatment of macular edema after retinal vein occlusion, age-related macular degeneration (wet), and diabetic macular edema.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 48349.6110
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For the treatment of patients with macular edema after retinal vein occlusion, age-related macular degeneration (wet), and diabetic macular edema.
Mechanism of action Ranibizumab binds to the receptor binding site of active forms of VEGF-A, including the biologically active, cleaved form of this molecule, VEGF110. The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.
Absorption After monthly intravitreal injections, maximum serum concentrations are minimal around 0.3 ng/mL to 2.36 ng/mL.
Protein binding Plasma protein binding is insignificant.
Biotransformation Metabolism was not quantified.
Route of elimination Not Available
Toxicity The most common toxic effects to the eye are eye pain, vitreous floaters, increased intraocular pressure, conjunctival hemorrhage, intraocular inflammation, and foreign body sensation. Also arterial thromboembolic events have occurred in patients.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions
  • No food effects found.

Targets


Vascular endothelial growth factor A
Name Vascular endothelial growth factor A
Gene Name VEGFA
Pharmacological action yes
Actions Not Available
References
  • Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V: Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci. 2005 Feb;46(2):726-33. - Pubmed
  • Michels S, Rosenfeld PJ: [Treatment of neovascular age-related macular degeneration with Ranibizumab/Lucentis] Klin Monatsbl Augenheilkd. 2005 Jun;222(6):480-4. - Pubmed
  • Rosenfeld PJ, Rich RM, Lalwani GA: Ranibizumab: Phase III clinical trial results. Ophthalmol Clin North Am. 2006 Sep;19(3):361-72. - Pubmed
  • Nguyen QD, Tatlipinar S, Shah SM, Haller JA, Quinlan E, Sung J, Zimmer-Galler I, Do DV, Campochiaro PA: Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol. 2006 Dec;142(6):961-9. Epub 2006 Aug 2. - Pubmed
  • Pieramici DJ, Avery RL: Ranibizumab: treatment in patients with neovascular age-related macular degeneration. Expert Opin Biol Ther. 2006 Nov;6(11):1237-45. - Pubmed
  • Gaudreault J, Fei D, Beyer JC, Ryan A, Rangell L, Shiu V, Damico LA: Pharmacokinetics and retinal distribution of ranibizumab, a humanized antibody fragment directed against VEGF-A, following intravitreal administration in rabbits. Retina. 2007 Nov-Dec;27(9):1260-6. - Pubmed
  • Ferrara N, Damico L, Shams N, Lowman H, Kim R: Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina. 2006 Oct;26(8):859-70. - Pubmed
  • Bakri SJ, Snyder MR, Reid JM, Pulido JS, Ezzat MK, Singh RJ: Pharmacokinetics of intravitreal ranibizumab (Lucentis). Ophthalmology. 2007 Dec;114(12):2179-82. - Pubmed
  • Kourlas H, Abrams P: Ranibizumab for the treatment of neovascular age-related macular degeneration: a review. Clin Ther. 2007 Sep;29(9):1850-61. - Pubmed
  • Spitzer MS, Ziemssen F, Bartz-Schmidt KU, Gelisken F, Szurman P: Treatment of age-related macular degeneration: focus on ranibizumab. Clin Ophthalmol. 2008 Mar;2(1):1-14. - Pubmed
DTHybrid score 0.4383

Predictions


Id Partner name Gene Name Score
5377 Placenta growth factor PGF 0.1355
1334 Tissue factor pathway inhibitor TFPI 0.0471
1719 Heparanase HPSE 0.0414
2058 P-selectin SELP 0.0373
309 Antithrombin-III SERPINC1 0.0304
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0257
587 Serum albumin ALB 0.0246
4411 DNA protection during starvation protein dps 0.0197
5423 UPF0010 protein HI1317 HI_1317 0.0197
3780 Lipoprotein nlpI precursor nlpI 0.0197
5424 Endonuclease VIII-like 1 NEIL1 0.0197
5787 Angiopoietin-1 receptor TEK 0.0182
4757 Cytochrome P450 2C9 CYP2C9 0.0178
3164 Biotin synthase bioB 0.0173
3186 Soluble calcium-activated nucleotidase 1 CANT1 0.0172
5036 Small inducible cytokine A8 CCL8 0.017
4385 Cytochrome c' Not Available 0.017
4967 Cytochrome c' cycA 0.017
5038 Cytochrome c' Not Available 0.017
5223 Cytochrome c' cycP 0.017
5012 Ig lambda chain V-II region MGC Not Available 0.017
3583 6-phosphogluconolactonase pgl 0.0159
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0157
3221 Cytochrome c4 cc4 0.0156
3259 Autolysin lytA 0.0151
5023 Glycoside hydrolase Not Available 0.0148
5024 Glycoside hydrolase Not Available 0.0148
4771 Dissimilatory copper-containing nitrite reductase nir 0.0148
5006 RNASE4 protein RNASE4 0.0148
6016 Cytochrome P450 2C19 CYP2C19 0.0146
113 S-adenosylmethionine decarboxylase proenzyme AMD1 0.0145
1654 Interleukin-1 beta IL1B 0.0145
844 Epidermal growth factor receptor EGFR 0.0145
4905 Cytochrome c2 Not Available 0.0143
4939 Cytochrome c2 cycA 0.0143
4964 Cytochrome c2 cycA 0.0143
4979 Cytochrome c2 cycA 0.0143
6673 Cytochrome c2 cycA 0.0143
3817 Complement C1q subcomponent subunit C C1QC 0.0138
3816 Complement C1q subcomponent subunit B C1QB 0.0138
3815 Complement C1q subcomponent subunit A C1QA 0.0138
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0137
494 Caspase-1 CASP1 0.0136
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.0136
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.0136
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.0136
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0136
3814 Complement C1r subcomponent C1R 0.0136
2149 Angiogenin ANG 0.0136
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.0135
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.013
1507 Cytochrome c CYCS 0.0126
3030 Salivary alpha-amylase AMY1A 0.0123
1374 Natriuretic peptides B NPPB 0.0122
1827 Gap junction alpha-1 protein GJA1 0.0121
1908 Vascular cell adhesion protein 1 VCAM1 0.0121
2723 Cholera enterotoxin subunit B ctxB 0.0118
22 30S ribosomal protein S4 rpsD 0.0117
6714 30S ribosomal protein S4 rpsD 0.0117
2077 Caspase-3 CASP3 0.0116
6374 Disintegrin and metalloproteinase domain-containing protein 28 ADAM28 0.0116
65 Matrix metalloproteinase-9 Not Available 0.0112
2430 Chondroitinase B cslB 0.0111
140 30S ribosomal protein S9 rpsI 0.011
6719 30S ribosomal protein S9 rpsI 0.011
6725 30S ribosomal protein S9 rpsI 0.011
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0103
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0103
275 Arachidonate 5-lipoxygenase ALOX5 0.0098
4513 Pancreatic alpha-amylase AMY2A 0.0098
862 Multidrug resistance-associated protein 1 ABCC1 0.0097
4512 Cytochrome P450 3A4 CYP3A4 0.0095
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0089
1024 Solute carrier family 22 member 11 SLC22A11 0.008
6143 Solute carrier family 22 member 7 SLC22A7 0.0079
6142 Solute carrier family 22 member 8 SLC22A8 0.007
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0064
3947 Xanthine dehydrogenase/oxidase XDH 0.0064
1729 Solute carrier family 22 member 6 SLC22A6 0.0064
193 Beta-1 adrenergic receptor ADRB1 0.0057
766 Beta-2 adrenergic receptor ADRB2 0.0056
556 Alpha-1A adrenergic receptor ADRA1A 0.005
20 Prostaglandin G/H synthase 1 PTGS1 0.0048
6024 Cytochrome P450 1A1 CYP1A1 0.0048
6013 Cytochrome P450 2E1 CYP2E1 0.0045
4200 Cytochrome P450 1A2 CYP1A2 0.004
1588 Multidrug resistance protein 1 ABCB1 0.0038
4119 Cytochrome P450 2D6 CYP2D6 0.0038
↑