Details of the Drug

General Information of Drug (ID: DME2H5T)

• Drug Name: Cilastatin
• Synonyms: Cilastatina; Cilastatine; Cilastatinum; Cilastatin Monosodium Salt; Cilastatin acid; Cilastatina [Spanish]; Cilastatine [French]; Cilastatinum [Latin]; MK0791; Cilastatin (INN); Cilastatin [INN:BAN]; MK-791; (2Z)-7-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}-2-({[(1S)-2,2-dimethylcyclopropyl]carbonyl}amino)hept-2-enoic acid; (Z)-(S)-6-carboxy-6-[(S)-2,2-dimethylcyclopropanecarboxamido]hex-5-enyl-L-cysteine; (Z)-7-[(2R)-2-amino-3-hydroxy-3-oxopropyl]sulfanyl-2-[[(1S)-2,2-dimethylcyclopropanecarbonyl]amino]hept-2-enoic acid

Indication

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[1]
Bacterial infection	1A00-1C4Z	Approved	[2]
Endometritis	N.A.	Approved	[1]
Peritonitis	N.A.	Approved	[1]
Pelvic inflammatory disease	GA05	Investigative	[1]

• Therapeutic Class: Antibiotics
• Affected Organisms: Humans and other mammals
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 358.5
  Logarithm of the Partition Coefficient (xlogp); -1
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Clearance: The renal clearance of drug is 0.10-0.16 L/h/kg [4]
  Elimination: Cilastatin is 70% excreted in the urine [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1 hour [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 59.78 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.6% [7]
  Vd: The volume of distribution (Vd) of drug is 14.6-20.1 L [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 25 mg/mL [3]
• Chemical Identifiers:
  Formula: C16H26N2O5S
  IUPAC Name: (Z)-7-[(2R)-2-amino-2-carboxyethyl]sulfanyl-2-[[(1S)-2,2-dimethylcyclopropanecarbonyl]amino]hept-2-enoic acid
  Canonical SMILES: CC1(C[C@@H]1C(=O)N/C(=C\\CCCCSC[C@@H](C(=O)O)N)/C(=O)O)C
  InChI: InChI=1S/C16H26N2O5S/c1-16(2)8-10(16)13(19)18-12(15(22)23)6-4-3-5-7-24-9-11(17)14(20)21/h6,10-11H,3-5,7-9,17H2,1-2H3,(H,18,19)(H,20,21)(H,22,23)/b12-6-/t10-,11+/m1/s1
  InChIKey: DHSUYTOATWAVLW-WFVMDLQDSA-N
• Cross-matching ID:
  PubChem CID: 6435415
  ChEBI ID: CHEBI:3697
  CAS Number: 82009-34-5
  UNII: 141A6AMN38
  DrugBank ID: DB01597
  TTD ID: D02GIU
  VARIDT ID: DR00505
• 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
Dehydropeptidase I (DPEP1)	TTYUENF	DPEP1_HUMAN	Inhibitor	[8]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Dipeptidase 1 (DPEP1)	OTVR8V1L	DPEP1_HUMAN	Gene/Protein Processing	[9]

References

• [1] Cilastatin 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: 5166).
• [3] BDDCS applied to over 900 drugs
• [4] Balfour JA, Bryson HM, Brogden RN: Imipenem/cilastatin: an update of its antibacterial activity, pharmacokinetics and therapeutic efficacy in the treatment of serious infections. Drugs. 1996 Jan;51(1):99-136. doi: 10.2165/00003495-199651010-00008.
• [5] FDA: Recarbrio Label
• [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] Pharmacokinetic study of pleural fluid penetration of carbapenem antibiotic agents in chemical pleurisy. Respir Med. 2006 Feb;100(2):324-31.
• [9] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.