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
Type-2 diabetes 5A11 Approved [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 472.5
Topological Polar Surface Area (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 [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 129 hours [3]
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 [3]
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

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 [4], [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Type-2 diabetes
ICD Disease Classification 5A11
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Dipeptidyl peptidase 4 (DPP-4) DTT DPP4 9.54E-01 -0.27 -1.85
P-glycoprotein 1 (ABCB1) DTP P-GP 2.30E-01 3.06E-01 7.43E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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] [23]
Arn-509 DMT81LZ Moderate Accelerated clearance of Linagliptin due to the transporter induction by Arn-509. Acute myeloid leukaemia [2A60] [23]
Gilteritinib DMWQ4MZ Moderate Decreased clearance of Linagliptin due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [24]
Erdafitinib DMI782S Moderate Decreased clearance of Linagliptin due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [25]
Tucatinib DMBESUA Moderate Decreased clearance of Linagliptin due to the transporter inhibition by Tucatinib. Breast cancer [2C60-2C6Y] [26]
PF-04449913 DMSB068 Moderate Decreased clearance of Linagliptin due to the transporter inhibition by PF-04449913. Chronic myelomonocytic leukaemia [2A40] [27]
Lumacaftor DMCLWDJ Moderate Accelerated clearance of Linagliptin due to the transporter induction by Lumacaftor. Cystic fibrosis [CA25] [28]
Tazemetostat DMWP1BH Moderate Increased metabolism of Linagliptin caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [23]
GS-5885 DMSL3DX Moderate Decreased clearance of Linagliptin due to the transporter inhibition by GS-5885. Hepatitis virus infection [1E50-1E51] [29]
PF-06463922 DMKM7EW Moderate Increased metabolism of Linagliptin caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [23]
Ibrutinib DMHZCPO Moderate Decreased clearance of Linagliptin due to the transporter inhibition by Ibrutinib. Mature B-cell lymphoma [2A85] [27]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Linagliptin caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [24]
Lasmiditan DMXLVDT Moderate Decreased clearance of Linagliptin due to the transporter inhibition by Lasmiditan. Migraine [8A80] [30]
Rolapitant DM8XP26 Moderate Decreased clearance of Linagliptin due to the transporter inhibition by Rolapitant. Nausea/vomiting [MD90] [31]
Abametapir DM2RX0I Moderate Decreased metabolism of Linagliptin caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [32]
Lefamulin DME6G97 Moderate Decreased metabolism of Linagliptin caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [33]
Enzalutamide DMGL19D Moderate Increased metabolism of Linagliptin caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [23]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Linagliptin caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [27]
Fostamatinib DM6AUHV Moderate Decreased clearance of Linagliptin due to the transporter inhibition by Fostamatinib. Thrombocytopenia [3B64] [34]
Elagolix DMB2C0E Moderate Increased metabolism of Linagliptin caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [23]
⏷ Show the Full List of 20 DDI Information of This Drug

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
⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug
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

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2 Clinical pipeline report, company report or official report of Boehringer Ingelheim.
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
5 Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 2009 Jan;10(1):71-87.
6 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
7 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
9 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
10 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
11 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
12 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
13 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
14 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
15 Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
16 Clinical pipeline report, company report or official report of Takeda (2009).
17 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
18 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. (Target id: 1612).
19 Diabetes Treatment. Diabetes Care. 2009 March; 32(3): e25-e30.
20 Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for type 2 diabetes. Cardiol Rev. 2010 Jul-Aug;18(4):213-7.
21 Clinical pipeline report, company report or official report of ShangHai APIs Chemical.
22 Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial. Diabetes Obes Metab. 2010 Apr;12(4):348-55.
23 Product Information. Tradjenta (linagliptin). Boehringer Ingelheim, Ridgefield, CT.
24 Cerner Multum, Inc. "Australian Product Information.".
25 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
26 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
27 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
28 Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.
29 Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
30 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
31 Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
32 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
33 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
34 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.