Identification
NameRamucirumab
Accession NumberDB05578
TypeBiotech
GroupsApproved, Investigational
Description

Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells. VEGFR stimulation also mediates downstream signalling required for angiogenesis and is postulated to be heavily involved in cancer progression, making it a highly likely drug target. In contrast to other agents directed against VEGFR-2, ramucirumab binds a specific epitope on the extracellular domain of VEGFR-2, thereby blocking all VEGF ligands from binding to it. Ramucirumab is indicated for us in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy.

Protein structureDb05578
Related Articles
Protein chemical formulaC6374H9864N1692O1996S46
Protein average weight143600.0 Da
Sequences
>9098_H|ramucirumab|Homo sapiens||H-GAMMA-1 (VH(1-116)+CH1(117-214)+HINGE-REGION(215-229)+CH2(230-339)+CH3(340-446))|||||||446||||MW 48696.0|MW 48696.0|
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYY
ADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTDAFDIWGQGTMVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
>9098_L|ramucirumab|Homo sapiens||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(109-214))|||||||214||||MW 23124.7|MW 23124.7|
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDASNLDTGVPS
RFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTKVDIKGTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
SynonymsNot Available
External IDs 1121B / IMC-1121B / LY3009806
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CyramzaSolution10 mgIntravenousEli Lilly & Co. Ltd.2015-09-10Not applicableCanada
CyramzaSolution10 mg/mLIntravenousEli Lilly & Co. Ltd.2014-04-21Not applicableUs
CyramzaSolution10 mg/mLIntravenousEli Lilly & Co. Ltd.2014-04-21Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIID99YVK4L0X
CAS number947687-13-0
Pharmacology
Indication

For use in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy.

Structured Indications
PharmacodynamicsNot Available
Mechanism of action

Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells.

TargetKindPharmacological actionActionsOrganismUniProt ID
Vascular endothelial growth factor receptor 2Proteinyes
antagonist
HumanP35968 details
Related Articles
AbsorptionNot Available
Volume of distribution

5.5 L

Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life

15 days

Clearance

0.014 L/hour

Toxicity

Ramucirumab packaging includes warnings for arterial thromboembolic events, hypertension, infusion-related reactions, gastrointestinal perforation, clinical deterioration in patients with cirrhosis, and reversible posterior leukoencephalopathy syndrome. The most common reactions observed in single-agent-treated patients at a rate of >10% and >2% higher than placebo were hypertension and diarrhea. The most common adverse reactions observed in patients treated with ramucirumab plus paclitaxel at a rate of of >30% and >2% higher than placebo plus paclitaxel were fatigue, neutropenia, diarrhea, and epistaxis.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ramucirumab.Approved
BelimumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Belimumab.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Ramucirumab.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Ramucirumab.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Ramucirumab.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Ramucirumab.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Ramucirumab.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Ramucirumab.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Ramucirumab.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Ramucirumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Ramucirumab.Investigational
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Ramucirumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Ramucirumab.Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Ramucirumab.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Ramucirumab.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Ramucirumab.Approved, Vet Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Ramucirumab.Approved
RindopepimutThe therapeutic efficacy of CDX-110 can be decreased when used in combination with Ramucirumab.Investigational
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Ramucirumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Ramucirumab.Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Ramucirumab.Approved, Investigational
Food InteractionsNot Available
References
Synthesis Reference

http://www.ema.europa.eu/docs/enGB/documentlibrary/EPAR-Publicassessmentreport/human/002829/WC500180726.pdf

General References
  1. Casak SJ, Fashoyin-Aje I, Lemery SJ, Zhang L, Jin R, Li H, Zhao L, Zhao H, Zhang H, Chen H, He K, Dougherty M, Novak R, Kennett S, Khasar S, Helms W, Keegan P, Pazdur R: FDA Approval Summary: Ramucirumab for Gastric Cancer. Clin Cancer Res. 2015 Aug 1;21(15):3372-6. doi: 10.1158/1078-0432.CCR-15-0600. Epub 2015 Jun 5. [PubMed:26048277 ]
  2. Aprile G, Rijavec E, Fontanella C, Rihawi K, Grossi F: Ramucirumab: preclinical research and clinical development. Onco Targets Ther. 2014 Oct 29;7:1997-2006. doi: 10.2147/OTT.S61132. eCollection 2014. [PubMed:25378934 ]
  3. Javle M, Smyth EC, Chau I: Ramucirumab: successfully targeting angiogenesis in gastric cancer. Clin Cancer Res. 2014 Dec 1;20(23):5875-81. doi: 10.1158/1078-0432.CCR-14-1071. Epub 2014 Oct 3. [PubMed:25281695 ]
  4. Aprile G, Bonotto M, Ongaro E, Pozzo C, Giuliani F: Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from benchside to clinical use. Drugs. 2013 Dec;73(18):2003-15. doi: 10.1007/s40265-013-0154-8. [PubMed:24277700 ]
  5. Goodkin R, Zaias B, Michelsen WJ: Arteriovenous malformation and glioma: coexistent or sequential? Case report. J Neurosurg. 1990 May;72(5):798-805. [PubMed:2182794 ]
  6. Grothey A, Galanis E: Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol. 2009 Sep;6(9):507-18. doi: 10.1038/nrclinonc.2009.110. Epub 2009 Jul 28. [PubMed:19636328 ]
  7. Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S, Leong S, O'Bryant C, Chow LQ, Serkova NJ, Meropol NJ, Lewis NL, Chiorean EG, Fox F, Youssoufian H, Rowinsky EK, Eckhardt SG: Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010 Feb 10;28(5):780-7. doi: 10.1200/JCO.2009.23.7537. Epub 2010 Jan 4. [PubMed:20048182 ]
  8. Lu D, Jimenez X, Zhang H, Bohlen P, Witte L, Zhu Z: Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy. Int J Cancer. 2002 Jan 20;97(3):393-9. [PubMed:11774295 ]
External Links
ATC CodesL01XC21 — Ramucirumab
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (493 KB)
MSDSDownload (206 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentCancers1
1CompletedNot AvailableAdvanced Solid Tumors1
1CompletedTreatmentAdenocarcinomas1
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentCancer, Breast / Metastatic Breast Cancer (MBC)1
1CompletedTreatmentCancers1
1CompletedTreatmentCarcinoma, Colorectal1
1CompletedTreatmentHepatocellular,Carcinoma1
1CompletedTreatmentStomach Neoplasms1
1CompletedTreatmentTumors, Solid1
1RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Biliary Tract Cancer / Gastric Adenocarcinoma / Non-Small-Cell Lung Carcinoma (NSCLC) / Transitional Cell Carcinoma1
1RecruitingTreatmentCancer, Advanced / Colorectal Cancers / Mantle Cell Lymphoma (MCL)1
1RecruitingTreatmentCentral nervous system neoplasms malignant NEC / Pediatric Solid Tumors / Recurrent Tumor / Refractory Tumors1
1RecruitingTreatmentCutaneous Melanoma / Microsatellite Instability-High (MSI-H) Solid Tumors / Tumors, Solid1
1RecruitingTreatmentEsophageal Cancers / Gastro-esophageal Cancer / Malignant Neoplasm of Stomach1
1RecruitingTreatmentEsophagogastric Adenocarcinoma1
1RecruitingTreatmentGastro-esophageal Junction Adenocarcinoma / Hepatocellular,Carcinoma / Tumors, Solid1
1RecruitingTreatmentGastroesophageal Junction Adenocarcinoma / Hepatocellular,Carcinoma / Malignant Neoplasm of Stomach / Non-Small-Cell Lung Carcinoma (NSCLC)1
1RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1RecruitingTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
1, 2Active Not RecruitingTreatmentCancer, Advanced / Gastric Adenocarcinoma / Gastroesophageal Junction Adenocarcinoma / Hepatocellular Cancer / Non-Small-Cell Lung Carcinoma (NSCLC) / Renal Cell Adenocarcinoma1
1, 2Not Yet RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Gastroesophageal Junction Adenocarcinoma / Metastatic Malignant Neoplasm in the Lymph Nodes / Recurrent Gastric Carcinoma / Stage IV Gastric Cancer / Stage IV Gastric Cancer AJCC v71
1, 2RecruitingTreatmentGastroesophageal Junction Region (GEJ) Cancer / Malignant Neoplasm of Stomach1
2Active Not RecruitingTreatmentBiliary Tract Cancer / Cancer, Advanced / Metastatic Cancers1
2Active Not RecruitingTreatmentCancer, Breast1
2Active Not RecruitingTreatmentGastric Adenocarcinoma / Gastroesophageal Junction Adenocarcinoma2
2Active Not RecruitingTreatmentHepatocellular,Carcinoma1
2Active Not RecruitingTreatmentMalignant Solid Tumours1
2Active Not RecruitingTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2Active Not RecruitingTreatmentTumors, Solid1
2CompletedNot AvailableCancers / Tumors, Solid1
2CompletedTreatmentAdult Glioblastoma Multiforme / Brain and Central Nervous System Tumors1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentCancer, Ovarian / Fallopian Tube Cancer / Primary Peritoneal Carcinoma1
2CompletedTreatmentCarcinoma of Renal Pelvis / Carcinoma of Ureter / Carcinoma of Urinary Tract / Urethral Carcinoma1
2CompletedTreatmentCarcinoma, Colorectal1
2CompletedTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
2CompletedTreatmentHepatocellular,Carcinoma1
2CompletedTreatmentMalignant Neoplasm of Colon / Rectal Carcinoma1
2CompletedTreatmentMalignant Neoplasm of Stomach1
2CompletedTreatmentMalignant Solid Tumours1
2CompletedTreatmentMetastatic Malignant Melanoma1
2CompletedTreatmentMetastatic Non-Small Cell Lung Cancer1
2CompletedTreatmentMetastatic Renal Cell Carcinoma1
2CompletedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentProstate Cancer1
2Not Yet RecruitingTreatmentGastric Adenocarcinoma / Gastro-esophageal Junction Adenocarcinoma1
2RecruitingTreatmentAdenocarcinomas1
2RecruitingTreatmentAdvanced Gastric or EGJ Cancer1
2RecruitingTreatmentBiliary Cancer1
2RecruitingTreatmentCarcinoid Tumors1
2RecruitingTreatmentColorectal Cancers1
2RecruitingTreatmentGastric Adenocarcinoma / Gastroesophageal Junction Adenocarcinoma1
2RecruitingTreatmentGastroesophageal Junction Adenocarcinoma / Metastatic Gastric Adenocarcinoma1
2RecruitingTreatmentGastroesophageal Junction Cancer / Malignant Neoplasm of Stomach1
2RecruitingTreatmentGastrooesophageal Cancer1
2RecruitingTreatmentMalignant Neoplasm of Pancreas1
2RecruitingTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2WithdrawnTreatmentStage IV Non-Small Cell Lung Cancer1
2, 3RecruitingTreatmentGastroesophageal Junction Cancer / Malignant Neoplasm of Stomach1
3Active Not RecruitingTreatmentCancer, Breast1
3Active Not RecruitingTreatmentGastroesophageal Junction Adenocarcinoma / Metastatic Gastric Adenocarcinoma1
3Active Not RecruitingTreatmentMalignant Neoplasm of Stomach1
3Active Not RecruitingTreatmentTransitional Cell Carcinoma1
3CompletedTreatmentAdenocarcinomas / Malignant Neoplasm of Stomach1
3CompletedTreatmentColorectal Cancers1
3CompletedTreatmentHepatocellular,Carcinoma1
3CompletedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
3RecruitingTreatmentGastric Adenocarcinoma / Gastroesophageal Junction Adenocarcinoma1
3RecruitingTreatmentHepatocellular,Carcinoma1
3RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
3RecruitingTreatmentStomach Neoplasms1
Not AvailableNo Longer AvailableNot AvailableGastroesophageal Junction Adenocarcinoma / Malignant Neoplasm of Stomach1
Not AvailableNo Longer AvailableNot AvailableMetastatic Adenocarcinoma of the Gastroesophageal Junction / Metastatic Gastric Cancers1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
SolutionIntravenous10 mg
SolutionIntravenous10 mg/mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2013067098 No2011-11-022031-11-02Us
Properties
StateSolid
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Vascular endothelial growth factor-activated receptor activity
Specific Function:
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domai...
Gene Name:
KDR
Uniprot ID:
P35968
Uniprot Name:
Vascular endothelial growth factor receptor 2
Molecular Weight:
151525.555 Da
References
  1. Goodkin R, Zaias B, Michelsen WJ: Arteriovenous malformation and glioma: coexistent or sequential? Case report. J Neurosurg. 1990 May;72(5):798-805. [PubMed:2182794 ]
Drug created on November 18, 2007 11:26 / Updated on August 17, 2016 12:24