Resiniferatoxin

Summary

Resiniferatoxin (CHEMBL17976) is a phase-3 clinical-stage small-molecule TRPV1 agonist targeting TRPV1, KCNA1, and KCNA2; indicated across 4 conditions including osteoarthritis, knee.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 6 (TRPV1, KCNA1, KCNA2…)
• Indications: 4 conditions
• Clinical trials: 11
• Chemistry: 628.7 Da · C37H40O9

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL17976
Name	Resiniferatoxin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	5702546
ChEBI	CHEBI:8809
Molecular formula	C37H40O9
Molecular weight	628.7
InChIKey	DSDNAKHZNJAGHN-MXTYGGKSSA-N

SMILES: C[C@@H]1C[C@]2([C@H]3[C@H]4[C@]1([C@@H]5C=C(C(=O)[C@]5(CC(=C4)COC(=O)CC6=CC(=C(C=C6)O)OC)O)C)O[C@](O3)(O2)CC7=CC=CC=C7)C(=C)C

IUPAC name: [(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-prop-1-en-2-yl-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)acetate

ChEBI definition: A heteropentacyclic compound found in Euphorbia poissonii with molecular formula C37H40O9. It is an agonist of the transient receptor potential cation channel subfamily V member 1 (TrpV1).

Pharmacological roles (ChEBI): TRPV1 agonist, neurotoxin, analgesic.

Other ChEBI roles (chemical / environmental): plant metabolite.

Also known as: Lopain, Mtx-071, MTX-71, Neuroclastin, Resiniferatoxin, RTX, Resiniferatoxin(RTX), resinferatoxin, SID26755740, resiniferatoxin, RESINIFERATOXIN

Patent coverage: 185 distinct patent families (428 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
TRPV1	TRPV1	Agonist	8.4	0.3%	Q8NER1
KCNA1	Kv1.1		5.1	0%	Q09470
KCNA2	Kv1.2	Pore blocker	4.5	0.7%	P16389
KCNA5	Kv1.5		4.6	0.2%	P22460
KCNA7	Kv1.7		4.7	0.5%	Q96RP8
KCNC1	Kv3.1		4.3	1.7%	P48547

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Microtubule-associated protein tau, Nuclear receptor ROR-gamma, Vanilloid receptor, Cruzipain, Transient receptor potential cation channel subfamily V member 1, Transient receptor potential cation channel subfamily V member 1.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 26 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TRPV1	10.72	EC50	0.02	nM	CHEMBL_ACT_1951484
TRPV1	10.72	EC50	0.02	nM	CHEMBL_ACT_3074179
O35433	10.7	Ki	0.02	nM	CHEMBL_ACT_1202798
O35433	10.64	Ki	0.02	nM	CHEMBL_ACT_783453
O35433	10.37	Ki	0.04	nM	CHEMBL_ACT_2389108
O35433	10.37	Ki	0.04	nM	CHEMBL_ACT_5138543
O35433	9.92	Ki	0.12	nM	CHEMBL_ACT_769153
O35433	9.89	Ki	0.13	nM	CHEMBL_ACT_997555
O35433	9.57	EC50	0.27	nM	CHEMBL_ACT_2389107
O35433	9.57	EC50	0.27	nM	CHEMBL_ACT_5138554
TRPV1	9.32	Ki	0.48	nM	CHEMBL_ACT_682734
TRPV1	9.04	EC50	0.92	nM	CHEMBL_ACT_13447271
TRPV1	9.04	EC50	0.92	nM	CHEMBL_ACT_13870241
TRPV1	8.91	Ki	1.23	nM	CHEMBL_ACT_13447283
TRPV1	8.91	Ki	1.23	nM	CHEMBL_ACT_13870249
O35433	8.8	EC50	1.6	nM	CHEMBL_ACT_769155
TRPV1	8.72	EC50	1.9	nM	CHEMBL_ACT_682735
O35433	8.36	Ki	4.4	nM	CHEMBL_ACT_778102
TRPV1	7.85	Ki	14	nM	CHEMBL_ACT_3597069
TRPV1	7.64	Ki	23.1	nM	CHEMBL_ACT_208354
O35433	7.24	EC50	57.5	nM	CHEMBL_ACT_778104
O35433	6.75	IC50	180	nM	CHEMBL_ACT_3597071

Target pathways

Aggregated over 6 target gene(s): TRPV1, KCNA1, KCNA2, KCNA5, KCNA7, KCNC1.

Top Reactome pathways

7 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	5	KCNA1, KCNA2, KCNA5, KCNA7, KCNC1
Potassium Channels	5	KCNA1, KCNA2, KCNA5, KCNA7, KCNC1
Voltage gated Potassium channels	5	KCNA1, KCNA2, KCNA5, KCNA7, KCNC1
TRP channels	1	TRPV1
Muscle contraction	1	KCNA5
Phase 3 - rapid repolarisation	1	KCNA5
Cardiac conduction	1	KCNA5

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	6
monoatomic ion transmembrane transport	6
transmembrane transport	6
action potential	5
protein homooligomerization	5
potassium ion transmembrane transport	5
potassium ion transport	5
sensory perception of pain	2
neuronal action potential	2
regulation of membrane potential	2
corpus callosum development	2
potassium ion export across plasma membrane	2
optic nerve development	2
regulation of presynaptic membrane potential	2
negative regulation of transcription by RNA polymerase II	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
osteoarthritis, knee	1	MONDO:0005416	EFO:0004616

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

Clinical trials

Total trials: 11.

Phase distribution

Phase	Trials
PHASE1	5
PHASE3	3
PHASE2	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04044742	PHASE3	WITHDRAWN	A Phase 3 Study to Evaluate the Efficacy and Safety of Resiniferatoxin for Pain Due to Osteoarthritis of the Knee
NCT04386980	PHASE3	WITHDRAWN	Study to Evaluate Resiniferatoxin in Patients With Knee Osteoarthritis Whose Total Knee Replacement Surgery is Delayed
NCT04572776	PHASE3	WITHDRAWN	Phase 3 Study to Assess Resiniferatoxin vs Standard of Care for the Treatment of Intractable Cancer Pain
NCT02522611	PHASE1/PHASE2	NOT_YET_RECRUITING	Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain
NCT04885972	PHASE2	UNKNOWN	Study to Evaluate Intra-articular Resiniferatoxin to Treat Moderate to Severe Pain From Knee Osteoarthritis
NCT05067257	PHASE2	SUSPENDED	Study to Assess Epidural Resiniferatoxin for the Treatment of Intractable Pain Associated With Advanced Cancer
NCT00804154	PHASE1	RECRUITING	Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer
NCT02566564	PHASE1	COMPLETED	Intra-articular Lopain (MTX-071) Phase I/IIa Study in Chronic Osteoarthritic Knee Joint Pain
NCT03226574	PHASE1	COMPLETED	Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain
NCT03542838	PHASE1	COMPLETED	Study of Resiniferatoxin for Knee Pain in Moderate to Severe Osteoarthritis
NCT05695339	PHASE1	COMPLETED	Resiniferatoxin for the Management of Refractory Morton s Neuroma Pain

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.

33 molecules share ≥1 primary target. Top 33 by shared-target count:

Molecule	Source	Status	Shared targets
Flecainide	ChEMBL + PubChem	Phase 4 (approved)	KCNA1, KCNA5, KCNA7
CAPSAICIN	ChEMBL + PubChem	Phase 4 (approved)	KCNA1, TRPV1
DALFAMPRIDINE	ChEMBL + PubChem	Phase 4 (approved)	KCNA1, KCNA5
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	KCNA1, KCNA5
QUINIDINE	ChEMBL + PubChem	Phase 4 (approved)	KCNA5, KCNA7
Diltiazem	PubChem	Approved	KCNA1, KCNA5
Dronedarone	ChEMBL + PubChem	Phase 4 (approved)	KCNA5
CANNABIDIOL	ChEMBL	Phase 4 (approved)	TRPV1
PROPOFOL	ChEMBL	Phase 4 (approved)	TRPV1
SERTINDOLE	ChEMBL	Phase 4 (approved)	KCNA5
VERNAKALANT	ChEMBL	Phase 4 (approved)	KCNA5
CORTISONE	ChEMBL + PubChem	Phase 3 (approved)	KCNA1
BERGAPTEN	ChEMBL	Phase 3	KCNA2
CANNABINOL	ChEMBL	Phase 3	TRPV1
FRAMYCETIN	ChEMBL	Phase 3	TRPV1
ZUCAPSAICIN	ChEMBL	Phase 3	TRPV1
BMS-919373	ChEMBL	Phase 2	KCNA5
CANNABIDIVARIN	ChEMBL	Phase 2	TRPV1
CANNABIGEROL	ChEMBL	Phase 2	TRPV1
ILEPCIMIDE	ChEMBL	Phase 2	TRPV1
JTS-653	ChEMBL	Phase 2	TRPV1
MAVATREP	ChEMBL	Phase 2	TRPV1
NGD-8243	ChEMBL	Phase 2	TRPV1
OLVANIL	ChEMBL	Phase 2	TRPV1
PIPERINE	ChEMBL	Phase 2	TRPV1
SB-705498	ChEMBL	Phase 2	TRPV1
TETRAHYDROCANNABIVARIN	ChEMBL	Phase 2	TRPV1
TETRYLAMMONIUM	ChEMBL	Phase 2	KCNA1
Amiodarone	PubChem	Approved	KCNA7
Belzutifan	PubChem	Approved	KCNA5
Lidocaine	PubChem	Approved	KCNA5
methoxsalen	PubChem	Approved	KCNA1
Verapamil	PubChem	Approved	KCNA7