Details of the Drug

General Information of Drug (ID: DMJTIYK)

• Drug Name: Ipilimumab
• Synonyms: BMS-734016; MDX-010; MDX-101; Yervoy (TN)

Indication

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[1]

• Affected Organisms: Humans and other mammals
• ATC Code:
  L01FX04: Ipilimumab
  L01FX: Other monoclonal antibodies and antibody drug conjugates
  L01F: MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Monoclonal antibody
• Sequence:
  >heavy chain
  QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYY
  ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSAS
  TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
  YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPS
  VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
  YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT
  KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
  GNVFSCSVMHEALHNHYTQKSLSLSPGK
  >light chain
  EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGAFSRATGIP
  DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFP
  PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL
  TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 65.8 mg/L [2]
  Clearance: The clearance of drug is 15.3 mL/h [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 14.7 days [3]
  Metabolism: The drug is metabolized via proteolytic enzymes [4]
  Vd: The volume of distribution (Vd) of drug is 7.21 L [3]
• Cross-matching ID:
  UNII: 6T8C155666
  DrugBank ID: DB06186
  TTD ID: D07BVI

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cytotoxic T-lymphocyte protein 4 (CTLA-4)	TTI2S1D	CTLA4_HUMAN	Not Available	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Melanoma
• ICD Disease Classification: 2C30

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cytotoxic T-lymphocyte protein 4 (CTLA-4)	DTT	CTLA4	2.73E-01	0.02	0.05

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Ipilimumab

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Vemurafenib	DM62UG5	Moderate	Increased risk of hepatotoxicity by the combination of Ipilimumab and Vemurafenib.	Melanoma [2C30]	[6]

Coadministration of a Drug Treating the Disease Different from Ipilimumab (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Ipilimumab and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[7]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Ipilimumab and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[8]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Ipilimumab and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[9]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Ipilimumab and Cannabidiol.	Epileptic encephalopathy [8A62]	[10]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Ipilimumab and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[11]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Ipilimumab and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[12]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Ipilimumab and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[13]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Ipilimumab and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[14]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Ipilimumab and Idelalisib.	Mature B-cell leukaemia [2A82]	[15]
Deflazacort	DMV0RNS	Moderate	Additive immunosuppressive effects by the combination of Ipilimumab and Deflazacort.	Muscular dystrophy [8C70]	[16]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6888).
• [2] FDA Approved Drug Products: Yervoy Ipilimumab Intravenous Injection
• [3] 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.
• [4] Minder EI, Barman-Aksoezen J, Schneider-Yin X: Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders. Clin Pharmacokinet. 2017 Aug;56(8):815-823. doi: 10.1007/s40262-016-0501-5.
• [5] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [6] Product Information. Yervoy (ipilimumab). Bristol-Myers Squibb, Princeton, NJ.
• [7] Cerner Multum, Inc. "Australian Product Information.".
• [8] Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
• [9] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [10] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [11] Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
• [12] Canadian Pharmacists Association.
• [13] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
• [14] Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
• [15] Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
• [16] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".