Cilastatin

Summary

Cilastatin (CHEMBL766) is an approved small-molecule protease inhibitor targeting DPEP1; indicated across 9 conditions including urinary tract infection and bacterial pneumonia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 1 (DPEP1)
• Indications: 9 conditions
• Clinical trials: 29
• Chemistry: 358.5 Da · C16H26N2O5S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL766
Name	Cilastatin
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	6435415
ChEBI	CHEBI:3697
Molecular formula	C16H26N2O5S
Molecular weight	358.5
InChIKey	DHSUYTOATWAVLW-WFVMDLQDSA-N

SMILES: CC1(C[C@@H]1C(=O)N/C(=C\CCCCSC[C@@H](C(=O)O)N)/C(=O)O)C

IUPAC name: (Z)-7-[(2R)-2-amino-2-carboxyethyl]sulfanyl-2-[[(1S)-2,2-dimethylcyclopropanecarbonyl]amino]hept-2-enoic acid

ChEBI definition: The thioether resulting from the formal oxidative coupling of the thiol group of L-cysteine with the 7-position of (2Z)-2-({[(1S)-2,2-dimethylcyclopropyl]carbonyl}amino)hept-2-enoic acid. It is an inhibitor of dehydropeptidase I (membrane dipeptidase, 3.4.13.19), an enzyme found in the brush border of renal tubes and responsible for degrading the antibiotic imipenem. Cilastatin is therefore administered (as the sodium salt) with imipenem to prolong the antibacterial effect of the latter by preventing its renal metabolism to inactive and potentially nephrotoxic products. Cilastatin also acts as a leukotriene D4 dipeptidase inhibitor, preventing the metabolism of leukotriene D4 to leukotriene E4.

Pharmacological roles (ChEBI): protease inhibitor, EC 3.4.13.19 (membrane dipeptidase) inhibitor.

Other ChEBI roles (chemical / environmental): xenobiotic, environmental contaminant.

Also known as: Cilastatin, Cilastatina, Cilastatine, Primaxin, SID50125939, CILASTATIN, Cilastatin sodiumÊ, Cilastatin sodiumÂ, Cilastatin Sodium, cilastatin

Parent form; salt/anhydrous children: CHEMBL1201057

Patent coverage: 3,060 distinct patent families (10,983 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
DPEP1	Dipeptidase 1	Inhibition	5.96	0.1%	P16444

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: 4’-phosphopantetheinyl transferase ffp, Dipeptidase 1.

Bioactivity

ChEMBL activities: 3 potent at pChembl ≥ 5 of 4 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P22412	6.96	Ki	110	nM	CHEMBL_ACT_1010566
P22412	6.72	Ki	190	nM	CHEMBL_ACT_989705
P22412	6.68	Ki	210	nM	CHEMBL_ACT_1025805

Target pathways

Aggregated over 1 target gene(s): DPEP1.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Synthesis of Leukotrienes (LT) and Eoxins (EX)	1	DPEP1
Aflatoxin activation and detoxification	1	DPEP1
LTC4-CYSLTR mediated IL4 production	1	DPEP1

Dominant GO biological processes

GO term	Targets
proteolysis	1
glutathione metabolic process	1
glutathione catabolic process	1
inflammatory response	1
antibiotic metabolic process	1
negative regulation of cell migration	1
neutrophil chemotaxis	1
homocysteine metabolic process	1
cellular response to calcium ion	1
cellular response to nitric oxide	1
lactam catabolic process	1
leukotriene D4 catabolic process	1
lipid metabolic process	1
leukotriene metabolic process	1

Indications & clinical

Indications

5 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
urinary tract infection	3	MONDO:0100338	EFO:0003103
bacterial pneumonia	3	MONDO:0004652	EFO:1001272
bacterial infectious disease	3	MONDO:0005113	EFO:0000771
pyelonephritis	3	MONDO:0006939	EFO:1001141
hematopoietic and lymphoid system neoplasm	2	MONDO:0002334	MONDO:0044881

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 29.

Phase distribution

Phase	Trials
PHASE2	11
PHASE3	7
PHASE1	6
PHASE4	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00445094	PHASE4	COMPLETED	A De-Escalating Strategy for Antibiotic Treatment of Pneumonia in The Medical Intensive Care Unit (0787B-092)
NCT01356472	PHASE4	UNKNOWN	Linezolid Alone or Combined With Carbapenem Against Methicillin-resistant Staphylococcus Aureus (MRSA) in Ventilator-associated Pneumonia
NCT01721408	PHASE4	COMPLETED	A Study To Determine The Efficacy And Safety Of Tigecycline Compared With Imipenem/Cliastatin to Treat Complicated Intra-Abdominal Infection
NCT05146154	PHASE4	WITHDRAWN	Impact of Obesity on the Pharmacokinetics of Imipenem-Relebactam in ICU Patients
NCT05561764	PHASE4	TERMINATED	Imipenem/Cilastatin/Relebactam Pharmacokinetics, Safety, and Outcomes in Adults and Adolescents With Cystic Fibrosis
NCT06569056	PHASE3	RECRUITING	A Trial of HRS-8427 in the Treatment of Adults With Complicated Urinary Tract Infection, Including Acute Pyelonephritis
NCT00080496	PHASE3	COMPLETED	Study Evaluating Tigecycline Versus Imipenem/Cilastatin in Hospital-Acquired Pneumonia
NCT02452047	PHASE3	COMPLETED	Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium+Imipenem+Cilastatin in Imipenem-Resistant Bacterial Infection (MK-7655A-013)
NCT02493764	PHASE3	COMPLETED	Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014)
NCT03894046	PHASE3	COMPLETED	Study to Evaluate the Efficacy and Safety of Intravenous Sulbactam-ETX2514 in the Treatment of Patients With Infections Caused by Acinetobacter Baumannii-calcoaceticus Complex
NCT05204563	PHASE3	COMPLETED	Imipenem/Cilastatin-XNW4107 Versus Imipenem/Cilastatin/Relebactam for Treatment of Participants With Bacterial Pneumonia (XNW4107-302, REITAB-2)
NCT05887908	PHASE3	COMPLETED	Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis
NCT06886464	PHASE2	RECRUITING	Prevention of Nephrotoxin-Induced Acute Kidney Injury Using Cilastatin
NCT07229040	PHASE2	RECRUITING	A Double-blind Non Inferiority Clinical Trial to Compare the Nephroprotection of Cilastatn Versus Thiosulfate in Patients Undergoing Debulking Surgery With Intraoperative Hyperthermic Intraperitoneal Chemotherapy With Cisplatin.
NCT07485010	PHASE2	NOT_YET_RECRUITING	Testing a Novel Combination Treatment (Arm D) Versus Standard of Care for Intensive Phase Treatment for Mycobacterium Abscessus Pulmonary Disease in People With or Without Cystic Fibrosis in the Finding the Optimal Regimen for Mycobacterium Abscessus Treatment (FORMaT) Adaptive Platform Trial
NCT00515034	PHASE2	COMPLETED	A Safety and Tolerability Study of Doripenem in Patients With Abdominal Infections or Pneumonia
NCT00690378	PHASE2	COMPLETED	Comparative Study of NXL104/Ceftazidime Versus Comparator in Adults With Complicated Urinary Tract Infections
NCT00707239	PHASE2	TERMINATED	Study Evaluating Safety and Efficacy of Tigecycline Versus Imipenem/Cilastatin Subjects With Hospital-Acquired Pneumonia
NCT01505634	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of MK-7655 (Relebactam) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone for Treating Complicated Urinary Tract Infection (cUTI) (MK-7655-003)
NCT01506271	PHASE2	COMPLETED	Study of the Safety, Tolerability, and Efficacy of Relebactam (MK-7655) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone to Treat Complicated Intra-Abdominal Infection [cIAI] (MK-7655-004)
NCT02321800	PHASE2	COMPLETED	A Study of Efficacy and Safety of Intravenous Cefiderocol (S-649266) Versus Imipenem/Cilastatin in Complicated Urinary Tract Infections
NCT04983901	PHASE2	COMPLETED	PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN
NCT06144060	PHASE2	UNKNOWN	A Trial of Intravenous HRS-8427 in the Treatment of Adults With Complicate Urinary Tract Infection, Including Acute Pyelonephritis
NCT01275170	PHASE1	COMPLETED	A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Participants With Impaired Renal Function (MK-7655-005)
NCT02971423	PHASE1	COMPLETED	Evaluation of the Safety, Tolerability and Pharmacokinetics of Intravenous ETX2514 Administered in Healthy Subjects
NCT03595189	PHASE1	COMPLETED	Safety, Tolerability and Pharmacokinetic Profile of an Infusion of Cilastatin in Healthy Volunteers.
NCT04787562	PHASE1	COMPLETED	Pharmacokinetics of XNW4107 in Subjects With Various Degrees of Renal Function
NCT04801043	PHASE1	COMPLETED	To Evaluate the Pharmacokinetics of XNW4107 in Healthy Adult Young Females and in Healthy Adult Elderly Males and Females.
NCT04802863	PHASE1	COMPLETED	Intrapulmonary Pharmacokinetics of XNW4107, Imipenem and Cilastatin in Healthy Subjects

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

1 molecules share ≥1 primary target. Top 1 by shared-target count:

Molecule	Source	Status	Shared targets
Imipenem	PubChem	Approved	DPEP1