Details of the Drug

General Information of Drug (ID: DM3FXPS)

• Drug Name: Liraglutide
• Synonyms: Liraglutida; Liraglutidum; Victoza; NN 2211; NN2211; Liraglutida [INN-Spanish]; Liraglutide [USAN:INN]; Liraglutidum [INN-Latin]; NN-2211; Victoza (TN); N26-(Hexadecanoyl-gamma-glutamyle)-(34-arginine)GLP-1-(7-37)-peptide; N26-(Hexadecanoyl-gamma-glutamyle)-(34-arginine)glucagon-like-peptide-1-(7-37)-peptide

Indication

Disease Entry	ICD 11	Status	REF
Non-insulin dependent diabetes	5A11	Approved	[1]
Type-2 diabetes	5A11	Approved	[2]
Obesity	5B81	Phase 2	[2]

• Drug Type: Small molecular drug
• Sequence: HAEGTFTSDVSSYLEGQAAKEEFIIAWLVKGRG
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 3751
  Logarithm of the Partition Coefficient (xlogp); -3.4
  Rotatable Bond Count (rotbonds); 132
  Hydrogen Bond Donor Count (hbonddonor); 54
  Hydrogen Bond Acceptor Count (hbondacc); 55
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 8 h [3]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
  Clearance: The clearance of drug is 1.2 L/h []
  Elimination: The drug is 6% excreted in urine and 5% excreted in feces [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 13 hours [5]
  Metabolism: The drug is metabolized via the dipeptidyl peptidase-4 and neutral endopeptidase to various smaller polypeptides [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.0069 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.01% [7]
  Vd: The volume of distribution (Vd) of drug is 13 L []
• Chemical Identifiers:
  Formula: C172H265N43O51
  IUPAC Name: (2S)-5-[[(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]propanoyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[2-[[(2S)-5-carbamimidamido-1-(carboxymethylamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-6-oxohexyl]amino]-2-(hexadecanoylamino)-5-oxopentanoic acid
  Canonical SMILES: CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC6=CN=CN6)N)C(=O)O
  InChI: InChI=1S/C172H265N43O51/c1-18-20-21-22-23-24-25-26-27-28-29-30-37-53-129(224)195-116(170(265)266)59-64-128(223)180-68-41-40-50-111(153(248)199-115(62-67-135(232)233)154(249)204-120(73-100-44-33-31-34-45-100)159(254)214-140(93(11)19-2)167(262)192-97(15)146(241)201-122(76-103-79-183-108-49-39-38-48-106(103)108)157(252)203-118(72-90(5)6)158(253)212-138(91(7)8)165(260)200-110(52-43-70-182-172(177)178)149(244)184-81-130(225)193-109(51-42-69-181-171(175)176)148(243)187-84-137(236)237)196-144(239)95(13)189-143(238)94(12)191-152(247)114(58-63-127(174)222)194-131(226)82-185-151(246)113(61-66-134(230)231)198-155(250)117(71-89(3)4)202-156(251)119(75-102-54-56-105(221)57-55-102)205-162(257)124(85-216)208-164(259)126(87-218)209-166(261)139(92(9)10)213-161(256)123(78-136(234)235)206-163(258)125(86-217)210-169(264)142(99(17)220)215-160(255)121(74-101-46-35-32-36-47-101)207-168(263)141(98(16)219)211-132(227)83-186-150(245)112(60-65-133(228)229)197-145(240)96(14)190-147(242)107(173)77-104-80-179-88-188-104/h31-36,38-39,44-49,54-57,79-80,88-99,107,109-126,138-142,183,216-221H,18-30,37,40-43,50-53,58-78,81-87,173H2,1-17H3,(H2,174,222)(H,179,188)(H,180,223)(H,184,244)(H,185,246)(H,186,245)(H,187,243)(H,189,238)(H,190,242)(H,191,247)(H,192,262)(H,193,225)(H,194,226)(H,195,224)(H,196,239)(H,197,240)(H,198,250)(H,199,248)(H,200,260)(H,201,241)(H,202,251)(H,203,252)(H,204,249)(H,205,257)(H,206,258)(H,207,263)(H,208,259)(H,209,261)(H,210,264)(H,211,227)(H,212,253)(H,213,256)(H,214,254)(H,215,255)(H,228,229)(H,230,231)(H,232,233)(H,234,235)(H,236,237)(H,265,266)(H4,175,176,181)(H4,177,178,182)/t93-,94-,95-,96-,97-,98+,99+,107-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,138-,139-,140-,141-,142-/m0/s1
  InChIKey: YSDQQAXHVYUZIW-QCIJIYAXSA-N
• Cross-matching ID:
  PubChem CID: 16134956
  ChEBI ID: CHEBI:71193
  CAS Number: 204656-20-2
  DrugBank ID: DB06655
  TTD ID: D03GOI
  INTEDE ID: DR0962
• 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
Glucagon-like peptide 1 receptor (GLP1R)	TTVIMDE	GLP1R_HUMAN	Agonist	[8]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Neprilysin (MME)	DEVN830	NEP_HUMAN	Substrate	[9]
Dipeptidyl peptidase IV (DPP4)	DEKZQY6	DPP4_HUMAN	Substrate	[9]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Gene/Protein Processing	[10]
Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33)	OTRZVI77	ADA33_HUMAN	Gene/Protein Processing	[10]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Gene/Protein Processing	[10]

Molecular Expression Atlas of This Drug

• The Studied Disease: Non-insulin dependent diabetes
• ICD Disease Classification: 5A11

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Glucagon-like peptide 1 receptor (GLP1R)	DTT	GLP1R	1.25E-01	0.17	1.26
Neprilysin (MME)	DME	MME	3.54E-01	4.98E-01	9.92E-01
Dipeptidyl peptidase IV (DPP4)	DME	DPP4	9.54E-01	-2.74E-01	-1.85E+00

References

• [1] Liraglutide FDA Label
• [2] 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: 1133).
• [3] Pavan-Langston D, Nelson DJ: Intraocular penetration of trifluridine. Am J Ophthalmol. 1979 Jun;87(6):814-8.
• [4] BDDCS applied to over 900 drugs
• [5] Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010 Nov;38(11):1944-53. doi: 10.1124/dmd.110.034066. Epub 2010 Aug 13.
• [6] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [7] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [8] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [9] Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010 Nov;38(11):1944-53.
• [10] Antitumoral activity of liraglutide, a new DNMT inhibitor in breast cancer cells in vitro and in vivo. Chem Biol Interact. 2021 Nov 1;349:109641. doi: 10.1016/j.cbi.2021.109641. Epub 2021 Sep 14.