Details of the Drug

General Information of Drug (ID: DMWFJTR)

• Drug Name: Linagliptin
• Synonyms: Ondero; BI 1356; BI-1356; Ondero (TN); BI-1356-BS; (R)-8-(3-Amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione

Indication

Disease Entry	ICD 11	Status	REF
Non-insulin dependent diabetes	5A11	Approved	[1]
Type 2 diabetes	5A11	Approved	[2]
Type-2 diabetes	5A11	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 472.5
  Logarithm of the Partition Coefficient (xlogp); 1.9
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 1.9 mL/min/kg [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 129 hours [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 16 L/kg [5]
• Chemical Identifiers:
  Formula: C25H28N8O2
  IUPAC Name: 8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione
  Canonical SMILES: CC#CCN1C2=C(N=C1N3CCC[C@H](C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C
  InChI: InChI=1S/C25H28N8O2/c1-4-5-13-32-21-22(29-24(32)31-12-8-9-17(26)14-31)30(3)25(35)33(23(21)34)15-20-27-16(2)18-10-6-7-11-19(18)28-20/h6-7,10-11,17H,8-9,12-15,26H2,1-3H3/t17-/m1/s1
  InChIKey: LTXREWYXXSTFRX-QGZVFWFLSA-N
• Cross-matching ID:
  PubChem CID: 10096344
  ChEBI ID: CHEBI:68610
  CAS Number: 668270-12-0
  DrugBank ID: DB08882
  TTD ID: D02EYG
  VARIDT ID: DR00745
  INTEDE ID: DR2673
  ACDINA ID: D01209
• 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
Dipeptidyl peptidase 4 (DPP-4)	TTDIGC1	DPP4_HUMAN	Inhibitor	[6]
HUMAN dipeptidyl peptidase 4 (DPP-4)	TTF928K	DPP4_HUMAN	Inhibitor	[7]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

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
Dipeptidyl peptidase 4 (DPP-4)	DTT	DPP4	5.40E-02	8.70E-03	1.20E-02
P-glycoprotein 1 (ABCB1)	DTP	P-GP	2.00E-01	2.57E-02	6.18E-02

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Linagliptin caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Arn-509	DMT81LZ	Moderate	Accelerated clearance of Linagliptin due to the transporter induction by Arn-509.	Acute myeloid leukaemia [2A60]	[9]
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[10]
Erdafitinib	DMI782S	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[11]
Tucatinib	DMBESUA	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by Tucatinib.	Breast cancer [2C60-2C6Y]	[12]
PF-04449913	DMSB068	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[13]
Lumacaftor	DMCLWDJ	Moderate	Accelerated clearance of Linagliptin due to the transporter induction by Lumacaftor.	Cystic fibrosis [CA25]	[14]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Linagliptin caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[9]
GS-5885	DMSL3DX	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by GS-5885.	Hepatitis virus infection [1E50-1E51]	[15]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Linagliptin caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
Ibrutinib	DMHZCPO	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by Ibrutinib.	Mature B-cell lymphoma [2A85]	[13]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Linagliptin caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[10]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[16]
Rolapitant	DM8XP26	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by Rolapitant.	Nausea/vomiting [MD90]	[17]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Linagliptin caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[18]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Linagliptin caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[19]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Linagliptin caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[9]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Linagliptin caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[13]
Fostamatinib	DM6AUHV	Moderate	Decreased clearance of Linagliptin due to the transporter inhibition by Fostamatinib.	Thrombocytopenia [3B64]	[20]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Linagliptin caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[9]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Haematite red	E00236	14833	Colorant
Copovidone	E00693	Not Available	Film/membrane-forming agent; Modified-release agent; Binding agent
Pregelatinized starch	E00674	Not Available	Binding agent; Diluent; Disintegrant

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Linagliptin 5mg tablet	5mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Linagliptin FDA Label
• [2] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 208026
• [3] 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: 6318).
• [4] ClinicalTrials.gov (NCT04371978) Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19. U.S. National Institutes of Health.
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [7] DPP4 inhibition: preventing SARS-CoV-2 infection and/or progression of COVID-19 Diabetes Metab Res Rev. 2020 Apr 26.
• [8] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [9] Product Information. Tradjenta (linagliptin). Boehringer Ingelheim, Ridgefield, CT.
• [10] Cerner Multum, Inc. "Australian Product Information.".
• [11] Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
• [12] Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
• [13] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [14] Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.
• [15] Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
• [16] Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
• [17] Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
• [18] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [19] Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
• [20] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.