Nafamostat

Summary

Nafamostat (CHEMBL273264) is a phase-3 clinical-stage small molecule targeting C1R, PRSS1, and TMPRSS2; indicated across 2 conditions including acute kidney injury and severe acute respiratory syndrome.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 8 (C1R, PRSS1, TMPRSS2…)
• Indications: 2 conditions
• Clinical trials: 2
• Chemistry: 347.4 Da · C19H17N5O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL273264
Name	Nafamostat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	4413
Molecular formula	C19H17N5O2
Molecular weight	347.4
InChIKey	MQQNFDZXWVTQEH-UHFFFAOYSA-N

SMILES: C1=CC(=CC=C1C(=O)OC2=CC3=C(C=C2)C=C(C=C3)C(=N)N)N=C(N)N

IUPAC name: (6-carbamimidoylnaphthalen-2-yl) 4-(diaminomethylideneamino)benzoate

Also known as: Nafamostat, SID26754619, SID29216079, SID89650190, nafamostat, nafomostat, NAFAMOSTAT

Parent form; salt/anhydrous children: CHEMBL1091841, CHEMBL3989553

Patent coverage: 2,407 distinct patent families (7,063 SureChEMBL compound mentions), from 6 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
C1R	complement C1r	Inhibition	4.92	0%	P00736
PRSS1	serine protease 1	Inhibition	7.77	0.2%	P07477
TMPRSS2	transmembrane serine protease 2	Inhibition	7	0.1%	O15393
TPSAB1	tryptase alpha/beta 1	Inhibition	10	3.1%	Q15661
TRPM7	TRPM7	Inhibition	3.21	62.2%	Q96QT4
ASIC1	ASIC1		4.9	2.6%	P78348
ASIC2	ASIC2		4.2	0.1%	Q16515
ASIC3	ASIC3		5.6	0%	Q9UHC3

Broader ChEMBL bioactivity targets: 40 (assay-derived). Sample: Microtubule-associated protein tau, Prelamin-A/C, Transmembrane protease serine 2, Plasminogen, 5-hydroxytryptamine receptor 2B, 5-hydroxytryptamine receptor 3A, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Amine oxidase [flavin-containing] A, Prothrombin.

Bioactivity

ChEMBL activities: 37 potent at pChembl ≥ 5 of 61 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ST14	10.7	Ki	0.02	nM	CHEMBL_ACT_15098312
ST14	10.7	Ki	0.02	nM	CHEMBL_ACT_15176549
TMPRSS2	9.3	IC50	0.5	nM	CHEMBL_ACT_25848520
HPN	9.28	Ki	0.53	nM	CHEMBL_ACT_15098342
HPN	9.28	Ki	0.53	nM	CHEMBL_ACT_15176510
TMPRSS2	9	IC50	1	nM	CHEMBL_ACT_25847345
HPN	8.3	IC50	5	nM	CHEMBL_ACT_18289616
LMNA	8.05	Potency	8.9	nM	CHEMBL_ACT_3648985
P00760	7.77	IC50	17	nM	CHEMBL_ACT_34203
PRSS1	7.77	IC50	17	nM	CHEMBL_ACT_489403
PRSS1	7.7	IC50	20	nM	CHEMBL_ACT_332928
HGFAC	7.6	Ki	25	nM	CHEMBL_ACT_15098332
HGFAC	7.6	Ki	25	nM	CHEMBL_ACT_15176531
C1S	7.54	IC50	29	nM	CHEMBL_ACT_18652423
F12	6.98	Ki	105	nM	CHEMBL_ACT_22793546
C1S	6.85	IC50	140	nM	CHEMBL_ACT_332927
HGFAC	6.82	IC50	150	nM	CHEMBL_ACT_15176544
PLG	6.62	IC50	240	nM	CHEMBL_ACT_332929
P35439	6.54	AC50	290	nM	CHEMBL_ACT_25120223
F2	6.54	IC50	290	nM	CHEMBL_ACT_332930
PLG	6.39	Ki	410	nM	CHEMBL_ACT_19054756
HGFAC	6.31	EC50	490	nM	CHEMBL_ACT_15102839
KLK1	6.19	IC50	650	nM	CHEMBL_ACT_332931
C1R	6.1	IC50	800	nM	CHEMBL_ACT_18652424
C1R	6	IC50	1000	nM	CHEMBL_ACT_332923
C1R	5.98	IC50	1040	nM	CHEMBL_ACT_332926
F2	5.72	IC50	1900	nM	CHEMBL_ACT_667294
SLC6A3	5.55	AC50	2800	nM	CHEMBL_ACT_25123521
PLG	5.54	IC50	2900	nM	CHEMBL_ACT_667295
ADRA2C	5.5	AC50	3200	nM	CHEMBL_ACT_25147438

Target pathways

Aggregated over 8 target gene(s): C1R, PRSS1, TMPRSS2, TPSAB1, TRPM7, ASIC1, ASIC2, ASIC3.

Top Reactome pathways

13 total, by targets touching each:

Pathway	Targets	Genes
Stimuli-sensing channels	3	ASIC1, ASIC2, ASIC3
Transport of small molecules	3	ASIC1, ASIC2, ASIC3
Ion channel transport	3	ASIC1, ASIC2, ASIC3
Activation of Matrix Metalloproteinases	2	PRSS1, TPSAB1
Initial triggering of complement	1	C1R
Classical antibody-mediated complement activation	1	C1R
TRP channels	1	TRPM7
Attachment and Entry	1	TMPRSS2
Induction of Cell-Cell Fusion	1	TMPRSS2
Uptake of dietary cobalamins into enterocytes	1	PRSS1
Regulation of Complement cascade	1	C1R
Developmental Lineage of Pancreatic Acinar Cells	1	PRSS1

Dominant GO biological processes

GO term	Targets
proteolysis	4
monoatomic ion transport	4
monoatomic ion transmembrane transport	4
sodium ion transport	3
response to acidic pH	3
sodium ion transmembrane transport	3
sensory perception of sour taste	3
monoatomic cation transport	3
establishment of localization in cell	3
extracellular matrix disassembly	2
calcium ion transport	2
calcium ion transmembrane transport	2
regulation of membrane potential	2
regulation of postsynapse assembly	2
detection of mechanical stimulus involved in sensory perception	2

Indications & clinical

Indications

2 indications (0 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
acute kidney injury	3	MONDO:0002492	HP:0001919
severe acute respiratory syndrome	3	MONDO:0005091	MONDO:0100096

Clinical trials

Total trials: 2.

Phase distribution

Phase	Trials
PHASE4	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01001403	PHASE4	COMPLETED	Effect of Nafamostat on Postreperfusion Syndrome (PRS)
NCT06676085	Not specified	RECRUITING	A Novel Strategy of ECMO Management Using Nafamostat for Regional Combined With Low Intensity Systematic Anticoagulation

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.

27 molecules share ≥1 primary target. Top 27 by shared-target count:

Molecule	Source	Status	Shared targets
Amiloride	ChEMBL + PubChem	Phase 4 (approved)	ASIC1, ASIC3
CAMOSTAT	ChEMBL	Phase 3	PRSS1, TMPRSS2
OTAMIXABAN	ChEMBL	Phase 3	PRSS1, TMPRSS2
PENTAMIDINE	ChEMBL + PubChem	Phase 4 (approved)	TMPRSS2
TANNIC ACID	ChEMBL + PubChem	Phase 4 (approved)	TMPRSS2
ARGATROBAN	ChEMBL	Phase 4 (approved)	PRSS1
BEROTRALSTAT	ChEMBL	Phase 4 (approved)	PRSS1
DEBRISOQUIN	ChEMBL	Phase 4 (approved)	TMPRSS2
MELAGATRAN	ChEMBL	Phase 4 (approved)	PRSS1
SULFAGUANIDINE	ChEMBL	Phase 4 (approved)	PRSS1
CAMOSTAT MESILATE	ChEMBL	Phase 3	PRSS1
DABIGATRAN	ChEMBL	Phase 3	PRSS1
GABEXATE	ChEMBL	Phase 3	TMPRSS2
MILVEXIAN	ChEMBL	Phase 3	PRSS1
PROPAMIDINE	ChEMBL	Phase 3	TMPRSS2
QUERCETIN	ChEMBL	Phase 3	PRSS1
RUTIN	ChEMBL	Phase 3	PRSS1
SILIBININ	ChEMBL	Phase 3	PRSS1
BAICALEIN	ChEMBL	Phase 2	PRSS1
DIMINAZENE	ChEMBL	Phase 2	TMPRSS2
EFEGATRAN	ChEMBL	Phase 2	PRSS1
SEPIMOSTAT	ChEMBL	Phase 2	PRSS1
Apixaban	PubChem	Approved	PRSS1
arginine	PubChem	Approved	TPSAB1
Aspirin	PubChem	Approved	ASIC3
Bromhexine	PubChem	Approved	TMPRSS2
Carfilzomib	PubChem	Approved	PRSS1