Zucapsaicin

Summary

Zucapsaicin (CHEMBL313971) is a phase-3 clinical-stage small molecule (ATC M02AB02) targeting TRPV1; indicated across 6 conditions including osteoarthritis, knee and dry eye syndrome.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: M02AB02
• Targets: 1 (TRPV1)
• Indications: 6 conditions
• Clinical trials: 114
• Chemistry: 305.4 Da · C18H27NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL313971
Name	Zucapsaicin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	1548942
ATC	M02AB02
Molecular formula	C18H27NO3
Molecular weight	305.4
InChIKey	YKPUWZUDDOIDPM-VURMDHGXSA-N

SMILES: CC(C)/C=C\CCCCC(=O)NCC1=CC(=C(C=C1)O)OC

IUPAC name: (Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide

Also known as: Cis-capsaicin, Civamide, Zucapsaicin, Zucapsaicina, Zucapsaicine, SID11112338, SID11113255, SID11113512, SID11113513, SID26719735, ZUCAPSAICIN, SID124882262

Patent coverage: 527 distinct patent families (2,469 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 2,462 (100%) 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
TRPV1	TRPV1	Activation	7.55	0.3%	Q8NER1

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Lysine-specific demethylase 4E, Lysosomal alpha-glucosidase, Cytochrome P450 2D6, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 3A4, Cruzipain, Aldehyde dehydrogenase 1A1, Cytochrome P450 2C19, Cellular tumor antigen p53.

Bioactivity

ChEMBL activities: 30 potent at pChembl ≥ 5 of 42 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TRPV1	7.55	EC50	28.2	nM	CHEMBL_ACT_19148119
CYP2C9	6.5	Potency	316.2	nM	CHEMBL_ACT_5061375
CYP2C9	6.5	AC50	316.2	nM	CHEMBL_ACT_6015119
TRPV1	5.97	Ki	1080	nM	CHEMBL_ACT_19148116
CYP2C9	5.9	Potency	1259	nM	CHEMBL_ACT_5061547
CYP2C9	5.9	AC50	1259	nM	CHEMBL_ACT_5991806
CYP1A2	5.8	AC50	1585	nM	CHEMBL_ACT_6016214
CYP1A2	5.8	AC50	1585	nM	CHEMBL_ACT_6068202
CYP2C9	5.7	Potency	1995	nM	CHEMBL_ACT_5065490
CYP2C9	5.7	AC50	1995	nM	CHEMBL_ACT_5995534
CYP1A2	5.5	AC50	3162	nM	CHEMBL_ACT_6003455
ALDH1A1	5.45	Potency	3548	nM	CHEMBL_ACT_4125076
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_4985581
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_4989776
CYP2C9	5.4	Potency	3981	nM	CHEMBL_ACT_5016934
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_5054570
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_5058698
CYP3A4	5.4	AC50	3981	nM	CHEMBL_ACT_6053738
CYP3A4	5.4	AC50	3981	nM	CHEMBL_ACT_6070112
CYP2C19	5.2	Potency	6310	nM	CHEMBL_ACT_4006123
P15917	5.2	Potency	6310	nM	CHEMBL_ACT_4651827
CYP2D6	5.2	Potency	6310	nM	CHEMBL_ACT_4973969
CYP2D6	5.2	AC50	6310	nM	CHEMBL_ACT_6045906
CYP2C19	5.2	AC50	6310	nM	CHEMBL_ACT_6056874
CYP2C19	5.1	Potency	7943	nM	CHEMBL_ACT_4014388
CYP3A4	5.1	Potency	7943	nM	CHEMBL_ACT_4997909
CYP3A4	5.1	Potency	7943	nM	CHEMBL_ACT_5066618
CYP2C19	5.1	AC50	7943	nM	CHEMBL_ACT_6012972
CYP3A4	5.1	AC50	7943	nM	CHEMBL_ACT_6013927
CYP2C19	5	Potency	10000	nM	CHEMBL_ACT_4018449

Target pathways

Aggregated over 1 target gene(s): TRPV1.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
TRP channels	1	TRPV1

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
fever generation	1
diet induced thermogenesis	1
peptide secretion	1
lipid metabolic process	1
cell surface receptor signaling pathway	1
chemosensory behavior	1
cellular response to heat	1
behavioral response to pain	1
sensory perception of taste	1
sensory perception of mechanical stimulus	1
thermoception	1
detection of temperature stimulus involved in thermoception	1
detection of temperature stimulus involved in sensory perception of pain	1
detection of chemical stimulus involved in sensory perception of pain	1

Indications & clinical

Indications

6 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	3	MONDO:0005416	EFO:0004616
dry eye syndrome	2	MONDO:0006733	EFO:1000906

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

Clinical trials

Total trials: 114.

Phase distribution

Phase	Trials
Not specified	43
PHASE3	15
PHASE4	13
PHASE2	13
PHASE1	13
EARLY_PHASE1	10
PHASE1/PHASE2	4
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00176969	PHASE4	COMPLETED	Response of Topical Capsaicin in Alopecia Areata
NCT00655811	PHASE4	COMPLETED	Ethnic Differences in Response to Topical Capsaicin: A Psychophysical Study on Healthy Subjects
NCT00697034	PHASE4	TERMINATED	Effects of Capsaicin on the Structure, Distribution, and Function of Cutaneous Small Nerve Fibers in Psoriatic Skin
NCT00771511	PHASE4	WITHDRAWN	Cervical Capsaicin for Labor Induction and Pain Relief
NCT01223820	PHASE4	COMPLETED	Neuro-immunological Analysis of Idiopathic Rhinitis Patients and Controls Treated With Capsaicin.
NCT01862523	PHASE4	COMPLETED	Mechanisms of Capsaicin Treatment in Idiopathic Rhinitis Patients and Controls
NCT01974037	PHASE4	COMPLETED	Capsaicin on Salty Gustatory Cortices
NCT02288156	PHASE4	COMPLETED	Elaboration of Patient-friendly Treatment Strategy With Capsaicin Nasal Spray in Patients With Idiopathic Rhinitis
NCT03124407	PHASE4	COMPLETED	Osteoarthritis Knee Pain Relief Study of 0.25% 920-CGS-200
NCT03348735	PHASE4	TERMINATED	Localized Neuropathic Pain: Topical Treatment Versus Systemic Treatment
NCT04238208	PHASE4	COMPLETED	The Efficacy and Safety Profile of Capsaicin 8% Patch Versus 5% Lidocaine Patch in Males With Diabetic Neuropathy
NCT04283292	PHASE4	COMPLETED	Capsaicin for the Treatment of Cannabinoid Hyperemesis Syndrome
NCT05298202	PHASE4	COMPLETED	The Influence of Capsaicin Gel During Exercise Within the Heat
NCT05840562	PHASE3	RECRUITING	Capsaicin 179 mg Patch Versus Oral Duloxetine in Patients With Chemotherapy-induced Peripheral Neuropathy
NCT05997979	PHASE3	RECRUITING	Analgesic Effectiveness of Capsaicin 8% Cutaneous Patch in Children
NCT00003610	PHASE3	COMPLETED	Capsaicin Lozenges in Treating Patients With Mucositis Caused by Radiation Therapy
NCT00033839	PHASE3	COMPLETED	A Phase III Study of Civamide Nasal Solution (Zucapsaicin) for the Treatment of Episodic Cluster Headache
NCT00069082	PHASE3	COMPLETED	Intranasal Civamide for Episodic Cluster Headache
NCT00077935	PHASE3	COMPLETED	Civamide in OA of the Knee(s)
NCT00993070	PHASE2/PHASE3	COMPLETED	Efficacy and Safety Study of Topical Capsaicin in Painful Diabetic Neuropathy
NCT00995306	PHASE3	COMPLETED	Evaluating the Safety and Efficacy Civamide in Osteoarthritis (OA) of the Knee(s)
NCT01231750	PHASE3	TERMINATED	Efficacy of Topical Capsaicin Cream for Stable Angina
NCT01533428	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of a Single Application of Capsaicin 8%Transdermal Delivery System Compared to Placebo in Reducing Pain Intensity in Subjects With Painful Diabetic Peripheral Neuropathy (PDPN)
NCT02700815	PHASE3	COMPLETED	Capsaicin + Diclofenac Gel in Acute Back Pain or Neck Pain
NCT02823912	PHASE2/PHASE3	UNKNOWN	Capsaicin Effect on Cytokines Profile in Dyslipidemia
NCT02854670	PHASE2/PHASE3	TERMINATED	A Study of the Effects of Topical Capsaicin in the Treatment of Provoked Vestibulodynia
NCT03153813	PHASE3	TERMINATED	Capsaicin Patches In Knee Osteoarthritis In Obese Patients
NCT03794388	PHASE3	COMPLETED	Evaluation in the Treatment of Neuropathic Pain Post Breast Surgery
NCT04967664	PHASE3	COMPLETED	Comparison of Qutenza (8% Capsaicin) With a Low-dose Capsaicin for Treatment of Nerve Pain After Surgery
NCT05029297	PHASE3	COMPLETED	Study With Two Capsaicin Topic Treatments in Diabetic Neuropathy.
NCT05093478	PHASE3	COMPLETED	The Prevalence of Local Immunoglobulin E (IgE) Elevation and Its Effect on Intranasal Capsaicin Therapy in the Non-allergic Rhinitis Population
NCT06807164	PHASE2	RECRUITING	Serratus Plane Block (SPB) Versus Capsaïcine Versus Botox-A for Chronic Neuropathic Pain in Post-mastectomy Syndrome
NCT00004316	PHASE1/PHASE2	COMPLETED	Phase I/II Randomized, Placebo-Controlled Study of Capsaicin for Interstitial Cystitis and Vulvar Vestibulitis
NCT00008476	PHASE2	COMPLETED	Capsaicin to Control Pain Following Third Molar Extraction
NCT00034710	PHASE2	COMPLETED	Pilot Study of High-Dose Capsaicin Patches to Treat Postherpetic Neuralgia Pain
NCT00693160	PHASE2	TERMINATED	Effect of Spinal Ketorolac After Acute Opioid Exposure
NCT00795106	PHASE2	WITHDRAWN	Trial to Evaluate the Efficacy of Topical Capsaicin to Reduce Pain and Improve Health-related Quality of Life in Adults With Chronic Myofascial Neck Pain
NCT00845923	PHASE2	COMPLETED	Evaluation of Civamide Patch in Treatment of Postherpetic Neuralgia and Post-Incisional Neuralgia
NCT00916942	PHASE2	COMPLETED	Study of NGX-4010 With the Use of Open Label Lidocaine (2.5%)/Prilocaine (2.5%) Cream for the Treatment of Postherpetic Neuralgia (PHN)
NCT02183519	PHASE1/PHASE2	COMPLETED	Respiratory Kinematics of Cough in Healthy Older Adults and Parkinson’s Disease

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.

16 molecules share ≥1 primary target. Top 16 by shared-target count:

Molecule	Source	Status	Shared targets
CANNABIDIOL	ChEMBL	Phase 4 (approved)	TRPV1
CAPSAICIN	ChEMBL	Phase 4 (approved)	TRPV1
PROPOFOL	ChEMBL	Phase 4 (approved)	TRPV1
CANNABINOL	ChEMBL	Phase 3	TRPV1
FRAMYCETIN	ChEMBL	Phase 3	TRPV1
RESINIFERATOXIN	ChEMBL	Phase 3	TRPV1
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