Cimetidine

Summary

Cimetidine (CHEMBL30) is an approved small-molecule H2-receptor antagonist (ATC A02BA51) targeting SLC29A4, SLC47A1, and SLC47A2; indicated across 17 conditions including gastroesophageal reflux disease and peptic ulcer disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A02BA51 (+1 more)
• Targets: 4 (SLC29A4, SLC47A1, SLC47A2…)
• Indications: 17 conditions
• Clinical trials: 21
• Chemistry: 252.34 Da · C10H16N6S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL30
Name	Cimetidine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2756
ChEBI	CHEBI:3699
ATC	A02BA51, A02BA01
Molecular formula	C10H16N6S
Molecular weight	252.34
InChIKey	AQIXAKUUQRKLND-UHFFFAOYSA-N

SMILES: CC1=C(N=CN1)CSCCNC(=NC)NC#N

IUPAC name: 1-cyano-2-methyl-3-[2-[(5-methyl-1H-imidazol-4-yl)methylsulfanyl]ethyl]guanidine

ChEBI definition: A member of the class of guanidines that consists of guanidine carrying a methyl substituent at position 1, a cyano group at position 2 and a 2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl group at position 3. It is a H2-receptor antagonist that inhibits the production of acid in stomach.

Pharmacological roles (ChEBI): H2-receptor antagonist, P450 inhibitor, anti-ulcer drug, analgesic, adjuvant.

Also known as: Acid-eze, Aciloc, Acinil, Acitak 200, Acitak 400, Acitak 800, Brumetidina, Brumetadina, Cimal, Cimetidina, Cimetidine, Cimetidinum

Parent form; salt/anhydrous children: CHEMBL1201051

Patent coverage: 15,118 distinct patent families (47,191 SureChEMBL compound mentions), from 15 matched compound structure(s). One matched structure accounts for 44,941 (95%) of the total. 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
SLC29A4	Plasma membrane monoamine transporter	Inhibition	3.3	0.7%	Q7RTT9
SLC47A1	Multidrug and toxin extrusion	Inhibition	6	0.5%	Q96FL8
SLC47A2	MATE2	Inhibition	5.1	0.6%	Q86VL8
HRH2	H2 receptor	Antagonist	6.85		P25021

Broader ChEMBL bioactivity targets: 27 (assay-derived). Sample: Survival motor neuron protein, Prelamin-A/C, 4’-phosphopantetheinyl transferase ffp, Organic anion transporter 3, Solute carrier family 22 member 2, Multidrug and toxin extrusion protein 1, Multidrug and toxin extrusion protein 2, Solute carrier family 22 member 2, Histamine H2 receptor, Thyrotropin receptor.

Bioactivity

ChEMBL activities: 44 potent at pChembl ≥ 5 of 65 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HRH2	7.16	Ki	70	nM	CHEMBL_ACT_13876515
HRH2	7.15	Ki	70.79	nM	CHEMBL_ACT_13876481
P08482	7.05	Potency	89.1	nM	CHEMBL_ACT_4803374
HRH2	6.85	Ki	140	nM	CHEMBL_ACT_13342027
HRH2	6.85	IC50	140	nM	CHEMBL_ACT_13342099
HRH2	6.77	Ki	170	nM	CHEMBL_ACT_2401823
HRH2	6.75	IC50	180	nM	CHEMBL_ACT_2401818
HRH2	6.71	AC50	196.1	nM	CHEMBL_ACT_25114371
P25102	6.6	Kd	251.2	nM	CHEMBL_ACT_331580
P25102	6.6	Kd	251.2	nM	CHEMBL_ACT_861733
P47747	6.58	Kd	263	nM	CHEMBL_ACT_1080369
HRH2	6.57	IC50	270	nM	CHEMBL_ACT_13336195
P47747	6.52	Ki	302	nM	CHEMBL_ACT_104840
P47747	6.43	Kd	371.5	nM	CHEMBL_ACT_561636
P47747	6.4	Kd	398.1	nM	CHEMBL_ACT_561635
HRH2	6.31	Ki	490	nM	CHEMBL_ACT_17995188
HRH2	6.3	IC50	500	nM	CHEMBL_ACT_17995173
P47747	6.3	Ki	501.2	nM	CHEMBL_ACT_515907
P47747	6.3	Ki	501.2	nM	CHEMBL_ACT_692885
HRH2	6.28	IC50	530	nM	CHEMBL_ACT_26333222
O08966	6.23	IC50	590	nM	CHEMBL_ACT_11000873
HRH2	6.11	IC50	781	nM	CHEMBL_ACT_2573329
HRH2	6.11	Ki	780	nM	CHEMBL_ACT_26333276
ATP4A	6.09	IC50	820	nM	CHEMBL_ACT_998186
SMN1	6.05	Potency	891.3	nM	CHEMBL_ACT_3889194
P47747	6.02	Kd	955	nM	CHEMBL_ACT_561634
P47747	6	Kd	1000	nM	CHEMBL_ACT_100381
HRH2	6	IC50	1000	nM	CHEMBL_ACT_16501819
HRH2	6	IC50	1000	nM	CHEMBL_ACT_16838425
P47747	5.99	IC50	1020	nM	CHEMBL_ACT_5166006

Target pathways

Aggregated over 4 target gene(s): SLC29A4, SLC47A1, SLC47A2, HRH2.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Transport of small molecules	3	SLC29A4, SLC47A1, SLC47A2
SLC-mediated transmembrane transport	3	SLC29A4, SLC47A1, SLC47A2
R-HSA-425366	2	SLC47A1, SLC47A2
SLC-mediated transport of organic cations	2	SLC47A1, SLC47A2
Histamine receptors	1	HRH2
G alpha (s) signalling events	1	HRH2
Transport of vitamins, nucleosides, and related molecules	1	SLC29A4
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane	1	SLC29A4

Dominant GO biological processes

GO term	Targets
obsolete organic cation transport	3
xenobiotic transport	2
monoatomic cation transmembrane transport	2
transmembrane transport	2
xenobiotic detoxification by transmembrane export across the plasma membrane	2
proton transmembrane transport	2
histamine metabolic process	1
neurotransmitter transport	1
obsolete serotonin transport	1
obsolete monoamine transport	1
obsolete dopamine transport	1
obsolete norepinephrine transport	1
adenosine transport	1
obsolete epinephrine transport	1
histamine transport	1

Indications & clinical

Indications

17 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
gastroesophageal reflux disease	4	MONDO:0007186	EFO:0003948
peptic ulcer disease	4	MONDO:0004247	HP:0004398
duodenal ulcer	4	MONDO:0005412	EFO:0004607
atopic eczema	3	MONDO:0004980	EFO:0000274
ulcer disease	3	MONDO:0043839	MONDO:0043839
endometrium neoplasm	2	MONDO:0021251	MONDO:0011962
breast carcinoma in situ	2	MONDO:0004658	MONDO:0004658
erythropoietic protoporphyria	2	MONDO:0001676	MONDO:0001676
breast carcinoma	2	MONDO:0004989	EFO:0000305
breast neoplasm	2	MONDO:0021100	MONDO:0007254
chronic obstructive pulmonary disease	1	MONDO:0005002	EFO:0000341
generalized anxiety disorder	1	MONDO:0001942	EFO:1001892
amyotrophic lateral sclerosis	1	MONDO:0004976	MONDO:0004976

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

Clinical trials

Total trials: 21.

Phase distribution

Phase	Trials
PHASE1	8
PHASE3	3
PHASE2	3
Not specified	3
PHASE4	2
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06056583	PHASE4	RECRUITING	Drug Excretion in Breast Milk
NCT01256879	PHASE4	COMPLETED	Cimetidine Biowaivers
NCT01757275	PHASE3	COMPLETED	High Dose Esomeprazole Na for Prevention of Rebleeding After Successful Endoscopic Therapy of a Bleeding Peptic Ulcer
NCT02157376	PHASE3	COMPLETED	Stress Ulcer Prophylaxis of Intravenous Esomeprazole in Chinese Seriously Ill Patients
NCT04018131	PHASE3	UNKNOWN	The Efficacy of Cimetidin for Acute - Extrinsic Atopic Dermatitis Treated With Standard Therapy
NCT04862585	PHASE2/PHASE3	COMPLETED	Safely Stopping Pre-medications in Patients With Breast Cancer Who Are Receiving Paclitaxel
NCT00002733	PHASE2	COMPLETED	Biological Therapy in Treating Patients With Metastatic Cancer
NCT00515073	PHASE2	COMPLETED	Papillary Serous Carcinoma of the Endometrium
NCT05020184	PHASE2	COMPLETED	Effect of Oral Cimetidine in the Protoporphyrias
NCT00800280	PHASE1	TERMINATED	Evaluating The Effects Of Cimetidine On The Elimination Of PD 0332334 From The Body
NCT02172417	PHASE1	COMPLETED	Tiotropium in Combination With Concomitant Cimetidine or Ranitidine in Healthy Male and Female Subjects
NCT02202512	PHASE1	COMPLETED	Effect of Repeated Doses of BI 1060469 and BI 1021958 on Glomerular Filtration Rate (GFR) in Healthy Volunteers
NCT03307252	PHASE1	COMPLETED	This Study Tests the Effect of Certain Medicines on the Transport of Other Medicines in the Body of Healthy Men
NCT03380455	PHASE1	COMPLETED	Effect of Cimetidine on the Pharmacokinetics of Lucerastat in Healthy Subjects
NCT03618316	PHASE1	COMPLETED	Effect of Cimetidine on the PK of Imeglimin
NCT04493931	PHASE1	COMPLETED	Drug-drug Interaction Study of Gepotidacin
NCT05881811	PHASE1	COMPLETED	The Drug-drug Interaction of HSK16149 Capsule With Probenecid Tablets or Cimetidine Tablets in Healthy Subjects
NCT05365451	EARLY_PHASE1	COMPLETED	Pharmacokinetic Drug-Drug Interaction Study to Identify Biomarkers of Kidney Transporters
NCT00002092	Not specified	COMPLETED	A Study to Evaluate the Effect of Cimetidine on CD4 Lymphocyte Counts in HIV Infection
NCT00475059	Not specified	COMPLETED	Performance of Cimetidine-corrected MDRD Equation in Renal Transplant Patients
NCT02555852	Not specified	COMPLETED	Proton Pump Inhibitors and Risk of Community-acquired Pneumonia

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

223 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Aripiprazole	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
CARVEDILOL	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
Dipyridamole	ChEMBL + PubChem	Phase 4 (approved)	SLC29A4, SLC47A1, SLC47A2
FAMOTIDINE	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
IMATINIB	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
MITOXANTRONE	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
ORPHENADRINE	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
Pimozide	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
Quinidine	ChEMBL + PubChem	Phase 4 (approved)	SLC29A4, SLC47A1, SLC47A2
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1, SLC47A2
Metformin	PubChem	Approved	SLC29A4, SLC47A1, SLC47A2
Amantadine	ChEMBL + PubChem	Phase 4 (approved)	SLC29A4, SLC47A1
BUSPIRONE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
Cetirizine	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1
CHLORHEXIDINE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
CLONIDINE	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1
DISOPYRAMIDE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
DOMPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
EPINASTINE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
ETHINYL ESTRADIOL	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
Fluoxetine	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC29A4
Histamine	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC29A4
IRINOTECAN	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
methylergonovine	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A1
ONDANSETRON	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
PANTOPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
PENTAMIDINE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
Pramipexole	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC47A2
PRAZOSIN	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
RIMANTADINE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
RITONAVIR	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
TOPOTECAN	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
TUBOCURARINE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
VECURONIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
Verapamil	ChEMBL + PubChem	Phase 4 (approved)	HRH2, SLC29A4
ZAFIRLUKAST	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1, SLC47A2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HRH2, SLC47A1
BITHIONOL	ChEMBL	Phase 4 (approved)	SLC47A1, SLC47A2
RANITIDINE	ChEMBL	Phase 4 (approved)	HRH2, SLC47A1
DABIGATRAN	ChEMBL + PubChem	Phase 3 (approved)	SLC47A1, SLC47A2
CAMOSTAT	ChEMBL	Phase 3	SLC47A1, SLC47A2
GABEXATE	ChEMBL	Phase 3	SLC47A1, SLC47A2
INDINAVIR	ChEMBL	Phase 3	SLC47A1, SLC47A2
NIFEKALANT	ChEMBL	Phase 3	SLC47A1, SLC47A2
Erythromycin	PubChem	Approved	HRH2, SLC47A1
Cinacalcet	ChEMBL + PubChem	Phase 4 (approved)	HRH2
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HRH2
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	HRH2
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	HRH2
LINAGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	HRH2
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HRH2
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	HRH2
SPIRONOLACTONE	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1
SUMATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1
TELMISARTAN	ChEMBL + PubChem	Phase 4 (approved)	SLC47A1
AMIODARONE	ChEMBL	Phase 4 (approved)	HRH2
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HRH2
AMLODIPINE	ChEMBL	Phase 4 (approved)	HRH2