Palonosetron

Summary

Palonosetron (CHEMBL1189679) is an approved small-molecule serotonergic antagonist (ATC A04AA55); indicated across 14 conditions including neoplasm and strabismus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A04AA55 (+1 more)
• Indications: 14 conditions
• Clinical trials: 79
• Chemistry: 296.4 Da · C19H24N2O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1189679
Name	Palonosetron
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	6337614
ChEBI	CHEBI:85161
ATC	A04AA55, A04AA05
Molecular formula	C19H24N2O
Molecular weight	296.4
InChIKey	CPZBLNMUGSZIPR-NVXWUHKLSA-N

SMILES: C1C[C@@H]2CN(C(=O)C3=CC=CC(=C23)C1)[C@@H]4CN5CCC4CC5

IUPAC name: (3aS)-2-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-3a,4,5,6-tetrahydro-3H-benzo[de]isoquinolin-1-one

ChEBI definition: An organic heterotricyclic compound that is an antiemetic used (as its hydrochloride salt) in combination with netupitant (under the trade name Akynzeo) to treat nausea and vomiting in patients undergoing cancer chemotherapy.

Pharmacological roles (ChEBI): antiemetic, serotonergic antagonist.

Also known as: (-)-palonosetron, NSC-743769, Palonosetron, Palonosetron, (3as, 3s)-, palonosetron, [3H]-Palonosetron, PALONOSETRON, Palonosetron HCl

Parent form; salt/anhydrous children: CHEMBL1720

Patent coverage: 2,368 distinct patent families (9,399 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 9,390 (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
	5-HT3A	Antagonist	10.49

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: Alpha-2A adrenergic receptor, Neuronal acetylcholine receptor subunit alpha-4, 5-hydroxytryptamine receptor 3A, Alpha-2C adrenergic receptor, Sodium channel protein type 5 subunit alpha, Serotonin 3 (5-HT3) receptor, Voltage-gated potassium channel, IKs; KCNQ1(Kv7.1)/KCNE1(MinK), Sodium-dependent serotonin transporter, Alpha-1A adrenergic receptor, Histamine H1 receptor, D(3) dopamine receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Muscarinic acetylcholine receptor M3, 5-hydroxytryptamine receptor 3B.

Bioactivity

ChEMBL activities: 34 potent at pChembl ≥ 5 of 41 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR3A	10.5	Ki	0.03	nM	CHEMBL_ACT_3533594
HTR3B	9.85	Kd	0.14	nM	CHEMBL_ACT_13844575
HTR3B	9.74	Kd	0.18	nM	CHEMBL_ACT_13844572
HTR3B	9.74	Kd	0.18	nM	CHEMBL_ACT_13844576
HTR3A	9.66	Kd	0.22	nM	CHEMBL_ACT_13844580
HTR3B	9.64	Kd	0.23	nM	CHEMBL_ACT_13844570
HTR3A	9.6	Kd	0.25	nM	CHEMBL_ACT_13844586
HTR3A	9.59	Kd	0.26	nM	CHEMBL_ACT_13844582
HTR3A	9.52	Kd	0.3	nM	CHEMBL_ACT_13844579
HTR3A	9.52	Kd	0.3	nM	CHEMBL_ACT_13844581
HTR3A	9.49	Kd	0.32	nM	CHEMBL_ACT_13844588
HTR3B	9.47	Kd	0.34	nM	CHEMBL_ACT_13844574
HTR3A	9.44	Kd	0.36	nM	CHEMBL_ACT_13844578
HTR3B	9.32	Kd	0.48	nM	CHEMBL_ACT_13844573
HTR3A	9.21	Kd	0.61	nM	CHEMBL_ACT_13844585
HTR3A	9.17	Kd	0.67	nM	CHEMBL_ACT_13844583
HTR3A	9.08	IC50	0.83	nM	CHEMBL_ACT_13843654
HTR3B	9.06	IC50	0.88	nM	CHEMBL_ACT_13843642
HTR3A	9.06	Kd	0.87	nM	CHEMBL_ACT_13844587
HTR3A	8.99	IC50	1.02	nM	CHEMBL_ACT_13843646
HTR3A	8.91	IC50	1.23	nM	CHEMBL_ACT_13843652
HTR3A	8.89	IC50	1.3	nM	CHEMBL_ACT_13843644
HTR3A	8.8	IC50	1.57	nM	CHEMBL_ACT_13843647
HTR3A	8.77	IC50	1.7	nM	CHEMBL_ACT_23313239
HTR3A	8.68	AC50	2.1	nM	CHEMBL_ACT_25148763
HTR3A	8.44	IC50	3.64	nM	CHEMBL_ACT_13843651
HTR3A	8.36	IC50	4.4	nM	CHEMBL_ACT_13843649
HTR3A	7.88	IC50	13.1	nM	CHEMBL_ACT_13843653
KCNH2	6.05	AC50	890	nM	CHEMBL_ACT_25117313
HRH1	5.96	AC50	1100	nM	CHEMBL_ACT_25212139
KCNH2	5.7	IC50	1995	nM	CHEMBL_ACT_15258093
SLC6A4	5.62	AC50	2400	nM	CHEMBL_ACT_25149979
KCNH2	5.4	IC50	3981	nM	CHEMBL_ACT_15258033
ADRA2C	5.4	AC50	4000	nM	CHEMBL_ACT_25147506

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

8 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
neoplasm	3	MONDO:0005070	EFO:0000616
strabismus	3	MONDO:0003432	HP:0000486
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
breast neoplasm	2	MONDO:0021100	EFO:0003869
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
brain cancer	2	MONDO:0001657	MONDO:0001657
glioma	2	MONDO:0021042	MONDO:0100342
melanoma	1	MONDO:0005105	EFO:0000756

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

Clinical trials

Total trials: 79.

Phase distribution

Phase	Trials
PHASE3	24
PHASE2	21
PHASE4	15
Not specified	13
PHASE2/PHASE3	2
PHASE1/PHASE2	2
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05841849	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of CINV in Breast Cancer
NCT00415103	PHASE4	COMPLETED	AMENO-2: Aprepitant Plus Palonosetron Versus Granisetron in the Prevention of Nausea and the Emesis Induced by Chemotherapy in Patients Treated With Haematopoietic Progenitors
NCT00684463	PHASE4	COMPLETED	Palonosetron in Moderately and Highly Emetogenic Chemotherapy Induced Nausea and Vomiting (Study P04935)(COMPLETED)
NCT00687011	PHASE4	COMPLETED	Palonosetron Plus Dexamethasone in Moderately Emetogenic Chemotherapy Induced Nausea and Vomiting (Study P04594)
NCT00952133	PHASE4	COMPLETED	Efficacy of IV Palo With IV Dexamethasone vs IV Palo for Prevention of Immediate & Delayed PONV
NCT02468323	PHASE4	COMPLETED	Prophylactic Antiemetic Efficacy of Palonosetron Versus Ondansetron for Cesarean Sections Under Regional Anesthesia
NCT02480088	PHASE4	COMPLETED	Comparison of Palonosetron and Ramosetron for Preventing Patient-controlled Analgesia Related Nausea and Vomiting Following Spine Surgery; Association With ABCB1 Polymorphism
NCT02532634	PHASE4	COMPLETED	Ramosetron, Aprepitant, and Dexamethasone Versus Palonosetron, Aprepitant, and Dexamethasone
NCT02541019	PHASE4	COMPLETED	Prophylactic Antiemetic Efficacy of Palonosetron Versus Ondansetron for the Prophylaxis of Postoperative Nausea and Vomiting (PONV) in Women Over 60 Years Undergoing Laparoscopic Cholecystectomy
NCT02809378	PHASE4	COMPLETED	The Effects of Anesthetic Techniques and Palonosetron Administration on the Incidence of PONV
NCT02941913	PHASE4	COMPLETED	Compare Between Two Doses of Palonosetron on the Prevention of Postoperative Nausea and Vomiting in Obese Patients
NCT03586817	PHASE4	UNKNOWN	PALONOSETRON X FOSAPREPITANT IN PONV
NCT04576390	PHASE4	UNKNOWN	Palonosetron Versus Ondansetron for PONV Prevention in Patients Undergoing ERCP
NCT04585412	PHASE4	COMPLETED	Evaluate Bioequivalence of Palonosetron (0.25mg/5mL)
NCT05956899	PHASE4	COMPLETED	Palonosetron vs Ondansetron In PONV Prophylaxis Among Idiopathic Scoliosis Patients
NCT03817970	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin Disposition and Kidney Injury
NCT00359567	PHASE3	COMPLETED	Comparative Study of Palonosetron With Granisetron as a Control in Patients Receiving Highly Emetogenic Chemotherapy
NCT00828295	PHASE3	COMPLETED	Safety and Efficacy of Palonosetron IV to Prevent Postoperative Nausea and Vomiting in Pediatric Patients
NCT01088022	PHASE3	UNKNOWN	Aprepitant for Prevention of Acute and Delayed Nausea and Vomiting in Patients Receiving a High-emetogenic Dose of Cyclophosphamide for Peripheral Blood Stem Cells Harvesting
NCT01339260	PHASE3	COMPLETED	An Efficacy and Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting
NCT01363479	PHASE3	COMPLETED	An Efficacy and Safety Study of Oral and Intravenous Palonosetron for the Prevention of Nausea and Vomiting
NCT01376297	PHASE3	COMPLETED	A Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting
NCT01395901	PHASE3	COMPLETED	Safety and Efficacy of Palonosetron IV to Prevent Postoperative Nausea and Vomiting in Pediatric Patients
NCT01442376	PHASE3	COMPLETED	Efficacy and Safety of Palonosetron Intravenous in Prevention of Chemotherapy Induced Nausea and Vomiting in Pediatric Patients
NCT01568268	PHASE3	COMPLETED	Therapeutic Efficacy and Safety of Palonosetron in Treatment of Postoperative Nausea and Vomiting
NCT02135510	PHASE3	COMPLETED	MEtoclopramide, DExamethasone or Axoli to Prevent or Delay Chemotherapy-induced Nausea and Vomiting in Moderately Emetogenic Non-AC-based Chemotherapy
NCT02203253	PHASE3	COMPLETED	Efficacy of Thalidomide in Preventing Chemotherapy-induced Delayed Nausea and Vomiting
NCT02484911	PHASE3	COMPLETED	Aprepitant ,Olanzapine,Palonosetron and Dexamethasone for the Prevention of Chemotherapy-induced Nausea and Vomiting
NCT02517021	PHASE3	COMPLETED	A Safety Study of Intravenous Pro-Netupitant and Palonosetron Combination for the Prevention of Nausea and Vomiting
NCT02557035	PHASE3	COMPLETED	An Efficacy and Safety Study of Intravenous Palonosetron Administered as an Infusion and as a Bolus for the Prevention of Nausea and Vomiting
NCT02933099	PHASE3	UNKNOWN	Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting
NCT03040726	PHASE2/PHASE3	COMPLETED	Netupitant and Palonosetron Hydrochloride in Preventing Chronic Nausea and Vomiting in Patients With Cancer
NCT03403712	PHASE3	COMPLETED	A Study to Assess the Safety and the Efficacy of IV Fosnetupitant/Palonosetron (260 mg/0.25 mg) Combination Compared to Oral Netupitant/Palonosetron (300 mg/0.5 mg) Combination for the Prevention of CINV in AC Chemotherapy in Women With Breast Cancer
NCT03606369	PHASE2/PHASE3	UNKNOWN	Effectiveness and Quality of Life Analysis of Palonosetron Against Ondansetron Combined With Dexamethasone and Fosaprepitant in Prevention of Acute and Delayed Emesis Associated to Chemotherapy Moderate and Highly Emetogenic in Breast Cancer.
NCT03674294	PHASE3	COMPLETED	Aprepitant Triple Therapy for the Prevention of CINV in Nondrinking and Young Women Who Received Moderately Emetogenic Chemotherapy
NCT04060771	PHASE3	UNKNOWN	Post-Operative Nausea and Vomiting in Children Submitted to Strabismus Surgery
NCT04201769	PHASE3	UNKNOWN	Dexamethasone-sparing Approach Including NEPA Against Emesis Caused by Cisplatin
NCT04912271	PHASE3	UNKNOWN	Granisetron Transdermal Patch for Prophylaxis of Delayed CINV
NCT05199818	PHASE3	UNKNOWN	Buccal Film vs IV Palonosetron for Prevention of CINV in Cancer Patients Receiving MEC
NCT05439798	PHASE3	UNKNOWN	Effect of Palonosetron, Ondansetron and Dexamethasone in the Prevention of Postoperative Nausea and Vomiting
NCT06554184	PHASE3	COMPLETED	HR20013 for Nausea and Vomiting Associated With Moderate Emetic Risk Anticancer Agents
NCT00306735	PHASE2	COMPLETED	Safety and Efficacy Study for the Prevention of Nausea and Vomiting in Multiple Myeloma Patients Receiving Stem Cell Transplantation.
NCT00412425	PHASE1/PHASE2	COMPLETED	Palonosetron for Prevention of Biochemotherapy Induced Nausea and Vomiting
NCT00503386	PHASE2	COMPLETED	Safety and Efficacy of Palonosetron in Preventing Chemotherapy-induced Nausea and Vomiting
NCT00600353	PHASE2	COMPLETED	Multi-day Doses in Prevention of Nausea and Emesis
NCT00666783	PHASE2	COMPLETED	An Efficacy and Safety Study of Palonosetron in Preventing Chemotherapy-Induced Nausea and Vomiting (CINV) in the Chinese Cancer Patients
NCT00900757	PHASE2	COMPLETED	Intravenous Palonosetron With Radiotherapy and Concomitant Temozolomide
NCT00967499	PHASE2	COMPLETED	Pilot Study to Assess Palonosetron Versus Ondansetron as Rescue Medication in Subjects That Develop Postoperative Nausea and Vomiting (PONV) in the Postanesthesia Care Unit (PACU)
NCT00982995	PHASE2	TERMINATED	Palonosetron for the Treatment of Nausea and Vomiting in Terminally Ill Patients
NCT01018758	PHASE2	COMPLETED	Study With Palonosetron Alone in Preventing Chemotherapy-induced Nausea and Vomiting in Untreated Patients With Aggressive Non Hodgkin’s Lymphomas Who Underwent Moderately Emetogenic Chemotherapy
NCT01031498	PHASE2	COMPLETED	Palonosetron Versus Ondansetron for the Prevention of Nausea and Vomiting
NCT01046240	PHASE1/PHASE2	COMPLETED	Pharmacokinetic Evaluation of Subcutaneous Versus Intravenous Palonosetron in Cancer Treated With Chemotherapy
NCT01370408	PHASE2	COMPLETED	Palonosetron, Ondansetron, and Dexamethasone for Delayed Nausea and Vomiting in Autologous Transplant Patients
NCT01909856	PHASE2	COMPLETED	The Efficacy and Safety of Palonosetron in Preventing the Gastrointestinal Reactions Induced by 3-day Highly Emetogenic Chemotherapy
NCT02205164	PHASE2	UNKNOWN	Palonosetron Plus Aprepitant Versus Palonosetron in Preventing Nausea and Vomiting in Leukemic Patients
NCT02290470	PHASE2	UNKNOWN	Olanzapine Against Delayed Nausea and Vomiting in Women Receiving Carboplatin Plus Paclitaxel
NCT02388750	PHASE2	COMPLETED	Prospective Study of Palonosetron in Radiation Induced Nausea and Vomiting (RINV)
NCT02445872	PHASE2	UNKNOWN	Safety and Efficacy of Aprepitant for CINV in Patients With Lung Cancer Receiving Multiple-day Cisplatin Chemotherapy
NCT03008213	PHASE2	TERMINATED	Combination of Netupitant and Palonosetron (Akynzeo®) in the Treatment of Refractory CINV
NCT03204279	PHASE2	COMPLETED	PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea and Vomiting
NCT03862144	PHASE2	COMPLETED	NEPA to Prevent Chemotherapy Induced Nausea and Vomiting in Patients With Breast Cancer
NCT03960151	PHASE2	WITHDRAWN	Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy
NCT04308837	PHASE2	UNKNOWN	A Phase II Trial of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) With Chemoradiation
NCT04592198	PHASE2	COMPLETED	Buccal Film Versus IV Injection Palonosetron for Moderately Emetogenic Chemotherapy Induced Nausea and Vomiting
NCT02650479	PHASE1	COMPLETED	Study of the Effects of Intravenous Exenatide on Cardiac Repolarization
NCT06427681	EARLY_PHASE1	NOT_YET_RECRUITING	An Relative Bioavailability Study of BH006 for Injection in Healthy Subjects
NCT07442890	Not specified	NOT_YET_RECRUITING	A Cohort Study on the Prevention of Nausea and Vomiting Induced by Concurrent Chemoradiotherapy for Lung Cancer Using Rolapitant and Palonosetron
NCT00661674	Not specified	COMPLETED	Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal
NCT01169805	Not specified	COMPLETED	Prophylactic Effects of Ondansetron, Ramosetron, and Palonosetron on Patient-Controlled Analgesia Related Nausea and Vomiting After Urologic Laparoscopic Surgery
NCT01476280	Not specified	COMPLETED	Palonosetron Versus Ramosetron for the Prevention of Postoperative Nausea and Vomiting
NCT01650961	Not specified	COMPLETED	The Effect of Palonosetron on the QTc Interval During Perioperative Period
NCT01825733	Not specified	COMPLETED	Comparison of Palonosetron and Ramosetron for Preventing Patient-controlled Analgesia Related Nausea and Vomiting Following Spine Surgery
NCT01952626	Not specified	COMPLETED	Prevention of Intrathecal Morphine Induced Pruritus: Comparison of Ondansetron and Palonosetron
NCT02597907	Not specified	COMPLETED	Postoperative Nausea and Vomiting: Ramosetron Plus Aprepitant vs Palonosetron Plus Aprepitant
NCT02625181	Not specified	COMPLETED	Real-time Decision Support for Postoperative Nausea and Vomiting (PONV) Prophylaxis
NCT02744508	Not specified	COMPLETED	Comparison of Palonosetron Versus Combination of Palonosetron and Dexamethasone for Preventing Postoperative Vomiting in Patients Receiving Fentanyl by Patient-controlled Analgesia After Minor Orthopedic Surgery
NCT02970643	Not specified	UNKNOWN	Proof-of-Concept Trial of Palonosetron and Olanzapine Without Dexamethasone for the Prevention of CIN
NCT03933605	Not specified	COMPLETED	Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy
NCT04533867	Not specified	COMPLETED	Palonosetron vs. Ondansetron for Postoperative Nausea and Vomiting in Bariatric Surgery

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

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).