Ipilimumab
Identification
- Summary
Ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody used to treat metastatic or unresectable melanoma.
- Brand Names
- Yervoy
- Generic Name
- Ipilimumab
- DrugBank Accession Number
- DB06186
- Background
Ipilimumab is a fully humanized IgG1 monoclonal antibody that blocks cytotoxic T lymphocyte antigen-4 (CTLA-4).5 Blocking CTLA-4 removes an inhibitory signal from reducing the activity of T lymphocytes.1,2,5 Ipilimumab was developed by Bristol-Myers Squibb and Medarex.5
Ipilimumab was granted FDA approval on 25 March 2011.5
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6572H10126N1734O2080S40
- Protein Average Weight
- 148000.0 Da
- Sequences
>Ipilimumab heavy chain (patent appl. US20150283234) QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSAS TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK
>Ipilimumab light chain EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGAFSRATGIP DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format- Synonyms
- Ipilimumab
- External IDs
- BMS-734016
- MDX-010
- MDX-101
- MDX-CTLA-4
- MOAB-CTLA-4
Pharmacology
- Indication
Ipilimumab is indicated to treat unresectable or metastatic melanoma, as an adjuvant in the treatment of cutaneous melanoma, to treat microsatellite-high or mismatch repair deficient metastatic colorectal cancer, or to treat hepatocellular carcinoma.5 Ipilimumab with nivolumab is indicated to treat advanced renal cell carcinoma.5
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Ipilimumab is a human IgG1 that binds CTLA-4, preventing 1 T-cell inhibition signal pathway.3 It has a long duration of action as it is given every 3 to 4 weeks.5 Patients should be counselled regarding the risk of immune-mediated adverse effects, infusion related reactions, and embryo-fetal toxicity.5
- Mechanism of action
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that competes with the stimulatory CD28 for binding to B7 on antigen presenting cells.3 CTLA-4 and CD28 are both presented on the surface of T-cells.3 Ipilimumab is a human IgG1 that binds CTLA-4, preventing the inhibition of T-cell mediated immune responses to tumors.3
Target Actions Organism ACytotoxic T-lymphocyte protein 4 inhibitorantibodyHumans - Absorption
Cmax was 65.8µg/mL for 2-6 year olds, 70.1µg/mL for 6-<12 year olds, and 73.3µg/mL in patients 12 years and older.5 Data regarding the AUC and Tmax of ipilumumab are not readily available.3,5
- Volume of distribution
The volume of distribution at steady-state of ipilimumab is 7.21L.3
- Protein binding
Data regarding the protein binding of ipilimumab is not readily available.5
- Metabolism
The metabolism of ipilimumab does not involve the cytochrome P450 enzyme system.5,6 Because ipilimumab is a protein, it is expected to be degraded into small peptides and amino acids by proteolytic enzymes.4
- Route of elimination
Data regarding the route of elimination of ipilimumab is not readily available.5
- Half-life
Ipilimumab has a half life of 14.7 days.3
- Clearance
Ipilimumab has a clearance of 15.3 mL/hr.3 Systemic clearance increases proportionally with body weight.6
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Data regarding ipilumumab overdose is not readily available.5 However, the most common adverse reactions to ipilumumab are fatigue, diarrhea, pruritus, rash, and colitis.5
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Ipilimumab which could result in a higher serum level. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Ipilimumab. Aceclofenac Aceclofenac may decrease the excretion rate of Ipilimumab which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Ipilimumab which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Ipilimumab which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Ipilimumab which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Ipilimumab which could result in a higher serum level. Aclidinium Ipilimumab may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Ipilimumab may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Ipilimumab which could result in a higher serum level. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Yervoy
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Yervoy Injection 5 mg/1mL Intravenous Baxter Pharmaceutical Solutions, LLC 2011-03-25 2016-04-11 US 
Yervoy Liquid 5 mg / mL Intravenous Bristol Myers Squibb 2012-03-08 Not applicable Canada 
Yervoy Injection 5 mg/1mL Intravenous E.R. Squibb & Sons, L.L.C. 2011-03-25 Not applicable US Yervoy Injection 5 mg/1mL Intravenous Baxter Pharmaceutical Solutions, LLC 2011-03-25 2016-04-11 US Yervoy Injection, solution, concentrate 5 mg/ml Intravenous Bristol Myers Squibb Pharma Eeig 2020-12-22 Not applicable EU 
Yervoy Injection 5 mg/1mL Intravenous E.R. Squibb & Sons, L.L.C. 2011-03-25 Not applicable US Yervoy Injection, solution, concentrate 5 mg/ml Intravenous Bristol Myers Squibb Pharma Eeig 2020-12-22 Not applicable EU
Categories
- ATC Codes
- L01XC11 — Ipilimumab
- Drug Categories
- Adjuvants, Immunologic
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- CTLA-4-directed Antibody Interactions
- CTLA-4-directed Blocking Antibody
- Drugs that are Mainly Renally Excreted
- Globulins
- Immune Checkpoint Inhibitors
- Immunoglobulin G
- Immunoglobulins
- Immunoproteins
- Immunotherapy
- Increased T Lymphocyte Activation
- Narrow Therapeutic Index Drugs
- Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6T8C155666
- CAS number
- 477202-00-9
References
- General References
- Johnson DB, Peng C, Abramson RG, Ye F, Zhao S, Wolchok JD, Sosman JA, Carvajal RD, Ariyan CE: Clinical Activity of Ipilimumab in Acral Melanoma: A Retrospective Review. Oncologist. 2015 Jun;20(6):648-52. doi: 10.1634/theoncologist.2014-0468. Epub 2015 May 11. [Article]
- Thumar JR, Kluger HM: Ipilimumab: a promising immunotherapy for melanoma. Oncology (Williston Park). 2010 Dec;24(14):1280-8. [Article]
- Trinh VA, Hagen B: Ipilimumab for advanced melanoma: a pharmacologic perspective. J Oncol Pharm Pract. 2013 Sep;19(3):195-201. doi: 10.1177/1078155212459100. Epub 2012 Oct 9. [Article]
- Fellner C: Ipilimumab (yervoy) prolongs survival in advanced melanoma: serious side effects and a hefty price tag may limit its use. P T. 2012 Sep;37(9):503-30. [Article]
- FDA Approved Drug Products: Yervoy Ipilimumab Intravenous Injection [Link]
- BC Cancer Agency: Yervoy Monograph [Link]
- External Links
- KEGG Drug
- D04603
- PubChem Substance
- 347910341
- 1094833
- ChEMBL
- CHEMBL1789844
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ipilimumab
- FDA label
- Download (1.13 MB)
- MSDS
- Download (479 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Lung Cancers 1 4 Active Not Recruiting Treatment Melanoma, Malignant 1 4 Active Not Recruiting Treatment Renal Cell Adenocarcinoma 1 4 Not Yet Recruiting Treatment Renal Cancers 1 4 Terminated Treatment Metastatic Melanoma 1 3 Active Not Recruiting Treatment Advanced Non Small Cell Lung Cancer (NSCLC) 1 3 Active Not Recruiting Treatment Advanced Renal Cell Carcinoma (aRCC) / Metastatic Renal Cell Carcinoma ( mRCC) 1 3 Active Not Recruiting Treatment Gastro Esophageal Junction Cancer / Malignant Neoplasm of Stomach 1 3 Active Not Recruiting Treatment Head and Neck Carcinoma 2 3 Active Not Recruiting Treatment Hepatocellular Carcinoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 5 mg/1mL Injection, solution, concentrate Intravenous 5 mg/ml Injection, solution, concentrate Intravenous; Parenteral 5 MG/ML Liquid Intravenous 5 mg / mL Injection, solution, concentrate Intravenous Injection, solution, concentrate Intravenous drip 5 g Solution Intravenous 50 mg Solution Intravenous 5 mg/1ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2381770 No 2007-08-07 2020-08-08 Canada
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 80-90 ºC (based on IgG properties) McConnell A., et al. (2014). MAbs. Sep-Oct; 6 (5); 1274-1282 boiling point (°C) Fab and Fc domains denaturates at 60 and 70 ºC respectively Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404 water solubility 50 mg/ml Human IgG purified. Product Information isoelectric point 6.1-8.5 Agrisera Information about IgG antibodies.
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InhibitorAntibody
- General Function
- Not Available
- Specific Function
- Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of t...
- Gene Name
- CTLA4
- Uniprot ID
- P16410
- Uniprot Name
- Cytotoxic T-lymphocyte protein 4
- Molecular Weight
- 24655.63 Da
References
- Yang JC, Hughes M, Kammula U, Royal R, Sherry RM, Topalian SL, Suri KB, Levy C, Allen T, Mavroukakis S, Lowy I, White DE, Rosenberg SA: Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother. 2007 Nov-Dec;30(8):825-30. [Article]
Drug created on March 19, 2008 16:16 / Updated on October 20, 2021 19:48