Prinomastat

Summary

Prinomastat (CHEMBL75094) is a phase-3 clinical-stage small-molecule antineoplastic agent targeting MMP13; indicated across 3 conditions including lung neoplasm and central nervous system neoplasm.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (MMP13)
• Indications: 3 conditions
• Clinical trials: 3
• Chemistry: 423.5 Da · C18H21N3O5S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL75094
Name	Prinomastat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	466151
ChEBI	CHEBI:138885
Molecular formula	C18H21N3O5S2
Molecular weight	423.5
InChIKey	YKPYIPVDTNNYCN-INIZCTEOSA-N

SMILES: CC1([C@@H](N(CCS1)S(=O)(=O)C2=CC=C(C=C2)OC3=CC=NC=C3)C(=O)NO)C

IUPAC name: (3S)-N-hydroxy-2,2-dimethyl-4-(4-pyridin-4-yloxyphenyl)sulfonylthiomorpholine-3-carboxamide

ChEBI definition: A hydroxamic acid that is (3S)-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide in which the hydrogen attached to the thiomorpholine nitrogen has been replaced by a [4-(pyridin-4-yloxy)phenyl]sulfonyl group. It is a selective inhibitor with of matrix metalloproteinases (MMPs) 2, 3, 9, 13, and 14.

Pharmacological roles (ChEBI): antineoplastic agent, matrix metalloproteinase inhibitor, EC 3.4.24.35 (gelatinase B) inhibitor.

Also known as: AG-3340, AG3340, KB-R-9896, Prinomastat, prinomastat, PRINOMASTAT

Patent coverage: 2,172 distinct patent families (8,839 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
MMP13	MMP13	Inhibition	10.4	0%	P45452

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Collagenase 3, Stromelysin-1, Matrix metalloproteinase-9, Interstitial collagenase, 72 kDa type IV collagenase, Disintegrin and metalloproteinase domain-containing protein 17, Matrix metalloproteinase-14, Matrilysin, Neutrophil collagenase.

Bioactivity

ChEMBL activities: 53 potent at pChembl ≥ 5 of 54 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MMP2	10.52	Ki	0.03	nM	CHEMBL_ACT_24998193
MMP3	10.52	Ki	0.03	nM	CHEMBL_ACT_24998198
MMP9	10.52	Ki	0.03	nM	CHEMBL_ACT_24998202
MMP13	10.52	Ki	0.03	nM	CHEMBL_ACT_24998213
MMP13	10.42	Ki	0.04	nM	CHEMBL_ACT_650068
MMP13	10.42	Ki	0.04	nM	CHEMBL_ACT_951078
MMP2	10.32	IC50	0.05	nM	CHEMBL_ACT_1149203
MMP9	10.32	IC50	0.05	nM	CHEMBL_ACT_1149207
MMP2	10.3	Ki	0.05	nM	CHEMBL_ACT_25004626
MMP2	10.3	Ki	0.05	nM	CHEMBL_ACT_845295
MMP2	10.1	Ki	0.08	nM	CHEMBL_ACT_596662
MMP2	10.08	Ki	0.08	nM	CHEMBL_ACT_650066
MMP2	10.08	Ki	0.08	nM	CHEMBL_ACT_951070
MMP2	10.05	IC50	0.09	nM	CHEMBL_ACT_1424616
MMP13	9.7	IC50	0.2	nM	CHEMBL_ACT_1149208
MMP9	9.7	IC50	0.2	nM	CHEMBL_ACT_195393
MMP9	9.7	IC50	0.2	nM	CHEMBL_ACT_92719
MMP3	9.64	IC50	0.23	nM	CHEMBL_ACT_1424617
MMP9	9.59	IC50	0.26	nM	CHEMBL_ACT_1424621
MMP9	9.59	Ki	0.26	nM	CHEMBL_ACT_25004625
MMP3	9.57	Ki	0.27	nM	CHEMBL_ACT_650067
MMP3	9.57	Ki	0.27	nM	CHEMBL_ACT_951072
MMP14	9.52	IC50	0.3	nM	CHEMBL_ACT_1424613
MMP2	9.52	IC50	0.3	nM	CHEMBL_ACT_269160
MMP2	9.3	IC50	0.5	nM	CHEMBL_ACT_195391
MMP13	9.3	IC50	0.5	nM	CHEMBL_ACT_269161
MMP2	9.3	IC50	0.5	nM	CHEMBL_ACT_92717
MMP8	9.27	IC50	0.54	nM	CHEMBL_ACT_1149206
MMP3	8.96	IC50	1.1	nM	CHEMBL_ACT_195392
MMP3	8.96	IC50	1.1	nM	CHEMBL_ACT_92718
MMP13	8.82	IC50	1.5	nM	CHEMBL_ACT_195394
MMP13	8.82	IC50	1.5	nM	CHEMBL_ACT_92720
MMP2	8.74	IC50	1.8	nM	CHEMBL_ACT_19277542
MMP9	8.48	IC50	3.3	nM	CHEMBL_ACT_19277576
MMP3	8.46	IC50	3.5	nM	CHEMBL_ACT_1149204
MMP1	8.31	IC50	4.9	nM	CHEMBL_ACT_951067
MMP3	8.31	IC50	4.9	nM	CHEMBL_ACT_951071
ADAM17	8.26	IC50	5.5	nM	CHEMBL_ACT_1150319
MMP1	8.24	IC50	5.7	nM	CHEMBL_ACT_1149202
MMP1	8.09	Ki	8.2	nM	CHEMBL_ACT_1096983
MMP1	8.09	IC50	8.2	nM	CHEMBL_ACT_1150320
MMP1	8.09	IC50	8.2	nM	CHEMBL_ACT_1424612
MMP1	8.09	Ki	8.2	nM	CHEMBL_ACT_650065
MMP1	8.09	Ki	8.2	nM	CHEMBL_ACT_951068
MMP1	8.08	Ki	8.3	nM	CHEMBL_ACT_24998188
ADAM17	7.66	IC50	22	nM	CHEMBL_ACT_2391972
MMP1	7.63	IC50	23.5	nM	CHEMBL_ACT_269162
MMP1	7.32	IC50	48	nM	CHEMBL_ACT_195390
MMP1	7.32	IC50	48	nM	CHEMBL_ACT_92716
MMP7	7.27	IC50	54	nM	CHEMBL_ACT_1424619
MMP7	7.27	Ki	54	nM	CHEMBL_ACT_951074
MMP7	7.14	IC50	72	nM	CHEMBL_ACT_1149205
MMP7	7.04	IC50	91	nM	CHEMBL_ACT_951073

Target pathways

Aggregated over 1 target gene(s): MMP13.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Collagen degradation	1	MMP13
Degradation of the extracellular matrix	1	MMP13
Extracellular matrix organization	1	MMP13
Collagen formation	1	MMP13
Activation of Matrix Metalloproteinases	1	MMP13
Assembly of collagen fibrils and other multimeric structures	1	MMP13
Generic Transcription Pathway	1	MMP13
RNA Polymerase II Transcription	1	MMP13
Gene expression (Transcription)	1	MMP13
Transcriptional regulation by RUNX2	1	MMP13
RUNX2 regulates genes involved in cell migration	1	MMP13

Dominant GO biological processes

GO term	Targets
endochondral ossification	1
growth plate cartilage development	1
proteolysis	1
extracellular matrix disassembly	1
extracellular matrix organization	1
bone mineralization	1
collagen catabolic process	1
bone morphogenesis	1
response to amyloid-beta	1

Indications & clinical

Indications

2 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
lung neoplasm	3	MONDO:0021117	MONDO:0008903
central nervous system neoplasm	2	MONDO:0006130	EFO:1000158

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

Clinical trials

Total trials: 3.

Phase distribution

Phase	Trials
PHASE3	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00003343	PHASE3	COMPLETED	Chemotherapy in Treating Patients Who Have Metastatic Prostate Cancer
NCT00004199	PHASE3	COMPLETED	Prinomastat and Combination Chemotherapy in Treating Patients With Metastatic or Recurrent Non-small Cell Lung Cancer
NCT00004200	PHASE2	COMPLETED	Prinomastat Plus Temozolomide Following Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

12 molecules share ≥1 primary target. Top 12 by shared-target count:

Molecule	Source	Status	Shared targets
CHLOROXINE	ChEMBL	Phase 4 (approved)	MMP13
DOXYCYCLINE	ChEMBL	Phase 4 (approved)	MMP13
CURCUMIN	ChEMBL	Phase 3	MMP13
MARIMASTAT	ChEMBL	Phase 3	MMP13
QUERCETIN	ChEMBL	Phase 3	MMP13
APRATASTAT	ChEMBL	Phase 2	MMP13
BATIMASTAT	ChEMBL	Phase 2	MMP13
CIPEMASTAT	ChEMBL	Phase 2	MMP13
CTS-1027	ChEMBL	Phase 2	MMP13
ILOMASTAT	ChEMBL	Phase 2	MMP13
LUTEOLIN	ChEMBL	Phase 2	MMP13
TANOMASTAT	ChEMBL	Phase 2	MMP13