Details of the Drug

General Information of Drug (ID: DM4EGV0)

• Drug Name: Linaclotide
• Synonyms: Linaclotide (USAN)

Indication

Disease Entry	ICD 11	Status	REF
Irritable bowel syndrome	DD91.0	Approved	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 1526.8
  Topological Polar Surface Area (xlogp); -6.8
  Rotatable Bond Count (rotbonds); 13
  Hydrogen Bond Donor Count (hbonddonor); 19
  Hydrogen Bond Acceptor Count (hbondacc); 28
• ADMET Property: Metabolism: The drug is metabolized via the loss of the terminal tyrosine moiety [3]
• Chemical Identifiers:
  Formula: C59H79N15O21S6
  IUPAC Name: (2S)-2-[[(1R,4S,7S,13S,16R,21R,24R,27S,30S,33R,38R,44S)-21-amino-13-(2-amino-2-oxoethyl)-27-(2-carboxyethyl)-44-[(1R)-1-hydroxyethyl]-30-[(4-hydroxyphenyl)methyl]-4-methyl-3,6,12,15,22,25,28,31,40,43,46,51-dodecaoxo-18,19,35,36,48,49-hexathia-2,5,11,14,23,26,29,32,39,42,45,52-dodecazatetracyclo[22.22.4.216,33.07,11]dopentacontane-38-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic acid
  Canonical SMILES: C[C@H]1C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)CNC(=O)[C@@H](NC2=O)[C@@H](C)O)C(=O)N[C@@H](CC4=CC=C(C=C4)O)C(=O)O)C(=O)N[C@@H](CSSC[C@@H](C(=O)N3)N)C(=O)N[C@H](C(=O)N5CCC[C@H]5C(=O)N1)CC(=O)N)CC6=CC=C(C=C6)O)CCC(=O)O
  InChI: InChI=1S/C59H79N15O21S6/c1-26-47(82)69-41-25-101-99-22-38-52(87)65-33(13-14-45(80)81)49(84)66-34(16-28-5-9-30(76)10-6-28)50(85)71-40(54(89)72-39(23-97-96-20-32(60)48(83)70-38)53(88)67-35(18-43(61)78)58(93)74-15-3-4-42(74)56(91)63-26)24-100-98-21-37(64-44(79)19-62-57(92)46(27(2)75)73-55(41)90)51(86)68-36(59(94)95)17-29-7-11-31(77)12-8-29/h5-12,26-27,32-42,46,75-77H,3-4,13-25,60H2,1-2H3,(H2,61,78)(H,62,92)(H,63,91)(H,64,79)(H,65,87)(H,66,84)(H,67,88)(H,68,86)(H,69,82)(H,70,83)(H,71,85)(H,72,89)(H,73,90)(H,80,81)(H,94,95)/t26-,27+,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,42-,46-/m0/s1
  InChIKey: KXGCNMMJRFDFNR-WDRJZQOASA-N
• Cross-matching ID:
  PubChem CID: 16158208
  ChEBI ID: CHEBI:68551
  CAS Number: 851199-59-2
  DrugBank ID: DB08890
  TTD ID: D00GNJ
  ACDINA ID: D00366

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Guanylyl cyclase C (GUCY2C)	TTLDPRG	GUC2C_HUMAN	Activator	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Irritable bowel syndrome
• ICD Disease Classification: DD91.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Guanylyl cyclase C (GUCY2C)	DTT	GUCY2C	9.52E-03	2.35	5.13

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Levonorgestrel	DM1DP7T	Moderate	Altered absorption of Linaclotide caused by Levonorgestrel.	Contraceptive management [QA21]	[9]
Oestradiol valerate and dienogest	DMZK0FQ	Moderate	Altered absorption of Linaclotide caused by Oestradiol valerate and dienogest.	Endometriosis [GA10]	[9]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Histidine	E00106	6274	Antioxidant; Buffering agent
Leucine	E00097	6106	Antiadherent; Flavoring agent; lubricant
Calcium chloride	E00474	5284359	Antimicrobial preservative; Desiccant
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Linaclotide 0.072 mg capsule	0.072 mg	Oral Capsule	Oral
Linaclotide 0.145 mg capsule	0.145 mg	Oral Capsule	Oral
Linaclotide 0.29 mg capsule	0.29 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 5017).
• [2] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [3] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [4] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] J Clin Oncol 31, 2013 (suppl; abstr TPS3646).
• [8] Discovery and optimization of a novel anti-GUCY2c x CD3 bispecific antibody for the treatment of solid tumors. MAbs. Jan-Dec 2021;13(1):1850395.
• [9] Cerner Multum, Inc. "UK Summary of Product Characteristics.".