Iclaprim

Summary

Iclaprim (CHEMBL134561) is a phase-3 clinical-stage small molecule (ATC J01EA03) targeting DHFR; indicated across 4 conditions including skin disorder and bacterial infectious disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: J01EA03
• Targets: 1 (DHFR)
• Indications: 4 conditions
• Clinical trials: 4
• Chemistry: 354.4 Da · C19H22N4O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL134561
Name	Iclaprim
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	213043
ChEBI	CHEBI:131751
ATC	J01EA03
Molecular formula	C19H22N4O3
Molecular weight	354.4
InChIKey	HWJPWWYTGBZDEG-UHFFFAOYSA-N

SMILES: COC1=C(C2=C(C=CC(O2)C3CC3)C(=C1)CC4=CN=C(N=C4N)N)OC

IUPAC name: 5-[(2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)methyl]pyrimidine-2,4-diamine

ChEBI definition: An aminopyrimidine that is 5-methylpyrimidine-2,4-diamine in which one of the hydrogens of the methyl group has been replaced by a 2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl group.

Also known as: AR-100, Iclaprim, Iclaprime, Ro-482622, ICLAPRIM, C0088816

Parent form; salt/anhydrous children: CHEMBL2105645

Patent coverage: 466 distinct patent families (962 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 681 (71%) 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
DHFR	dihydrofolate reductase	Inhibition	6.11	69.8%	P00374

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Dihydrofolate reductase, Dihydrofolate reductase, Dihydrofolate reductase, Dihydrofolate reductase.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 13 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P0A017	10.1	Ki	0.08	nM	CHEMBL_ACT_13939399
P0A017	10.09	Ki	0.08	nM	CHEMBL_ACT_6329028
P0A017	9.05	Ki	0.9	nM	CHEMBL_ACT_6328204
P0A017	8.66	IC50	2.2	nM	CHEMBL_ACT_5225699
P0A017	8.59	IC50	2.6	nM	CHEMBL_ACT_5225730
P0ABQ4	8.15	IC50	7	nM	CHEMBL_ACT_1116518
P0A017	8.15	IC50	7	nM	CHEMBL_ACT_1116519
DHFR	8.1	IC50	8	nM	CHEMBL_ACT_1116520
P0A017	7.57	IC50	27	nM	CHEMBL_ACT_5225731
P0ABQ4	7.18	IC50	65.35	nM	CHEMBL_ACT_25656892
DHFR	6.11	Ki	775	nM	CHEMBL_ACT_13939370
DHFR	6.11	Ki	775	nM	CHEMBL_ACT_6329080
P16184	5.62	IC50	2400	nM	CHEMBL_ACT_1116521

Target pathways

Aggregated over 1 target gene(s): DHFR.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	1	DHFR
Metabolism of folate and pterines	1	DHFR
G1/S-Specific Transcription	1	DHFR

Dominant GO biological processes

GO term	Targets
tetrahydrobiopterin biosynthetic process	1
one-carbon metabolic process	1
negative regulation of translation	1
axon regeneration	1
response to methotrexate	1
dihydrofolate metabolic process	1
tetrahydrofolate metabolic process	1
tetrahydrofolate biosynthetic process	1
folic acid metabolic process	1
regulation of removal of superoxide radicals	1

Indications & clinical

Indications

4 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
skin disorder	3	MONDO:0005093	EFO:0000701
bacterial infectious disease	3	MONDO:0005113	EFO:0000771

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

Clinical trials

Total trials: 4.

Phase distribution

Phase	Trials
PHASE3	3
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00303550	PHASE3	COMPLETED	Study of Intravenous (I.V.) Iclaprim Versus Linezolid in Complicated Skin and Skin Structure Infections [cSSSI] (ASSIST-2)
NCT02600611	PHASE3	COMPLETED	Phase 3 Study to Evaluate Safety and Efficacy of Iclaprim Versus Vancomycin for ABSSSI: REVIVE-1
NCT02607618	PHASE3	COMPLETED	Phase 3 Study to Evaluate Safety and Efficacy of Iclaprim Versus Vancomycin for ABSSSI: REVIVE-2
NCT00543608	PHASE2	TERMINATED	Clinical Efficacy of Intravenous Iclaprim Versus Vancomycin in the Treatment of Hospital-Acquired, Ventilator-Associated, or Health-Care-Associated Pneumonia

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.

22 molecules share ≥1 primary target. Top 22 by shared-target count:

Molecule	Source	Status	Shared targets
LEUCOVORIN	ChEMBL + PubChem	Phase 4 (approved)	DHFR
METHOTREXATE	ChEMBL + PubChem	Phase 4 (approved)	DHFR
PEMETREXED	ChEMBL + PubChem	Phase 4 (approved)	DHFR
DIFLUNISAL	ChEMBL	Phase 4 (approved)	DHFR
GENTAMICIN	ChEMBL	Phase 4 (approved)	DHFR
MEFENAMIC ACID	ChEMBL	Phase 4 (approved)	DHFR
PRALATREXATE	ChEMBL	Phase 4 (approved)	DHFR
PYRIMETHAMINE	ChEMBL	Phase 4 (approved)	DHFR
RALTITREXED	ChEMBL	Phase 4 (approved)	DHFR
SULFACETAMIDE	ChEMBL	Phase 4 (approved)	DHFR
SULFADIAZINE	ChEMBL	Phase 4 (approved)	DHFR
TERIFLUNOMIDE	ChEMBL	Phase 4 (approved)	DHFR
TRIMETHOPRIM	ChEMBL	Phase 4 (approved)	DHFR
TRIMETREXATE	ChEMBL	Phase 4 (approved)	DHFR
AMINOPTERIN	ChEMBL	Phase 2	DHFR
BREQUINAR	ChEMBL	Phase 2	DHFR
CYCLOGUANIL	ChEMBL	Phase 2	DHFR
DIAVERIDINE	ChEMBL	Phase 2	DHFR
EDATREXATE	ChEMBL	Phase 2	DHFR
EPIROPRIM	ChEMBL	Phase 2	DHFR
PIRITREXIM	ChEMBL	Phase 2	DHFR
Folic Acid	PubChem	Approved	DHFR