Details of the Drug

General Information of Drug (ID: DMLOS5R)

• Drug Name: BAY 80-6946
• Synonyms: Copanlisib; BAY-80-6946; Aliqopa; UNII-WI6V529FZ9; BAY80-6946; WI6V529FZ9; AK172384; BAY 80-6946 (Copanlisib); Copanlisib [USAN:INN]; Copanlisib (USAN/INN); GTPL7875; SCHEMBL1655478; SCHEMBL13084037; Copanlisib (BAY 80-6946); DTXS

Indication

Disease Entry	ICD 11	Status	REF
Follicular lymphoma	2A80	Approved	[1]
Non-hodgkin lymphoma	2B33.5	Approved	[2]

• ATC Code:
  L01EM02: BAY 80-6946
  L01EM: Phosphatidylinositol-3-kinase (Pi3K) inhibitors
  L01E: PROTEIN KINASE INHIBITORS
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 480.5
  Logarithm of the Partition Coefficient (xlogp); 0.3
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 9
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 463 mcg/L []
  Clearance: The clearance of drug is 17.9 L/h []
  Elimination: Copanlisib is excreted approximately 50% as unchanged compound and 50% as metabolites in humans []
  Half-life: The concentration or amount of drug in body reduced by one-half in 14.6 - 82 hours []
  Metabolism: The drug is metabolized via the CYP3A and CYP1A1 []
  Vd: The volume of distribution (Vd) of drug is 871 L []
• Chemical Identifiers:
  Formula: C23H28N8O4
  IUPAC Name: 2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]pyrimidine-5-carboxamide
  Canonical SMILES: COC1=C(C=CC2=C3NCCN3C(=NC(=O)C4=CN=C(N=C4)N)N=C21)OCCCN5CCOCC5
  InChI: InChI=1S/C23H28N8O4/c1-33-19-17(35-10-2-6-30-8-11-34-12-9-30)4-3-16-18(19)28-23(31-7-5-25-20(16)31)29-21(32)15-13-26-22(24)27-14-15/h3-4,13-14,25H,2,5-12H2,1H3,(H2,24,26,27)
  InChIKey: MWYDSXOGIBMAET-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 135565596
  CAS Number: 1032568-63-0
  UNII: WI6V529FZ9
  DrugBank ID: DB12483
  TTD ID: D0S5LD
  INTEDE ID: DR0378
  ACDINA ID: D00965
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase alpha (PIK3CA)	TTEUNMR	PK3CA_HUMAN	Inhibitor	[1]
PI3-kinase delta (PIK3CD)	TTGBPJE	PK3CD_HUMAN	Inhibitor	[1]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Modulator	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Post-Translational Modifications	[5]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Protein Interaction/Cellular Processes	[5]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Protein Interaction/Cellular Processes	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Follicular lymphoma
• ICD Disease Classification: 2A80

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
PI3-kinase gamma (PIK3CG)	DTT	PIK3CG	1.98E-01	-0.05	-0.55
Cytochrome P450 1A1 (CYP1A1)	DME	CYP1A1	6.63E-01	3.55E-01	4.13E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.76E-01	-4.64E-01	-9.16E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from BAY 80-6946 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Bay 80-6946 caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[6]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Bay 80-6946 caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[6]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Bay 80-6946 caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[6]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Bay 80-6946 caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[6]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Bay 80-6946 and Ozanimod.	Multiple sclerosis [8A40]	[7]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Bay 80-6946 caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[8]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Kyselina citronova	E00014	311	Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium hydroxide	E00234	14798	Alkalizing agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Copanlisib 60 mg For Injection	60 mg	For Injection	Intravenous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
• [4] FDA label of Copanlisib. The 2020 official website of the U.S. Food and Drug Administration.
• [5] PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. Toxicol Appl Pharmacol. 2019 Oct 15;381:114729. doi: 10.1016/j.taap.2019.114729. Epub 2019 Aug 22.
• [6] Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT.
• [7] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [8] Cerner Multum, Inc. "Australian Product Information.".