Mitoxantrone

Summary

Mitoxantrone (CHEMBL58) is an approved small-molecule antineoplastic agent (ATC L01DB07) targeting TOP2A; indicated across 28 conditions including neoplasm and acute myeloid leukemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01DB07
• Targets: 1 (TOP2A)
• Indications: 28 conditions
• Clinical trials: 178
• Chemistry: 444.5 Da · C22H28N4O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL58
Name	Mitoxantrone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4212
ChEBI	CHEBI:50729
ATC	L01DB07
Molecular formula	C22H28N4O6
Molecular weight	444.5
InChIKey	KKZJGLLVHKMTCM-UHFFFAOYSA-N

SMILES: C1=CC(=C2C(=C1NCCNCCO)C(=O)C3=C(C=CC(=C3C2=O)O)O)NCCNCCO

IUPAC name: 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione

ChEBI definition: A dihydroxyanthraquinone that is 1,4-dihydroxy-9,10-anthraquinone which is substituted by 6-hydroxy-1,4-diazahexyl groups at positions 5 and 8.

Pharmacological roles (ChEBI): antineoplastic agent, analgesic.

Also known as: Misostol, Mitoxantrona, Mitoxantrone, NSC-279836, mitoxantrone, mitoxanthrone, SID11111482, SID11111483, SID90341083, Mitoxanthrone, SID85856281, SID92763439

Parent form; salt/anhydrous children: CHEMBL1200827, CHEMBL1417019

Patent coverage: 40,866 distinct patent families (166,878 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 166,372 (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
TOP2A	DNA topoisomerase II alpha	Inhibition	5.28	99.6% (common-essential)	P11388

Broader ChEMBL bioactivity targets: 67 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Pyruvate kinase PKM, Ubiquitin carboxyl-terminal hydrolase 2, Survival motor neuron protein, Prelamin-A/C, ATP-dependent DNA helicase Q1, RecQ-like DNA helicase BLM, Inositol monophosphatase 1, Ferritin light chain, Thrombopoietin.

Bioactivity

ChEMBL activities: 60 potent at pChembl ≥ 5 of 97 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ABCC1	8.82	IC50	1.5	nM	CHEMBL_ACT_11000468
ABCC1	8.82	IC50	1.5	nM	CHEMBL_ACT_11000469
ABCC1	8.72	IC50	1.9	nM	CHEMBL_ACT_11000470
THPO	7.6	Potency	25.1	nM	CHEMBL_ACT_4813343
THPO	7.6	Potency	25.1	nM	CHEMBL_ACT_5074296
ABCC1	7.56	IC50	27.5	nM	CHEMBL_ACT_18918288
LMNA	7.15	Potency	70.8	nM	CHEMBL_ACT_3667599
CHRM2	7.11	Ki	77.9	nM	CHEMBL_ACT_7779794
CHRM4	7.05	Ki	89.8	nM	CHEMBL_ACT_7779798
MTOR	6.83	Potency	146.9	nM	CHEMBL_ACT_4522098
CHRM1	6.74	Ki	180.3	nM	CHEMBL_ACT_7779792
SLC47A1	6.72	IC50	190	nM	CHEMBL_ACT_12636124
CHRM2	6.66	IC50	219	nM	CHEMBL_ACT_7779793
SLC47A1	6.4	IC50	400	nM	CHEMBL_ACT_12636133
SLC47A2	6.28	IC50	530	nM	CHEMBL_ACT_12636142
SLC47A1	6.28	IC50	530	nM	CHEMBL_ACT_12637813
CHRM4	6.19	IC50	644.1	nM	CHEMBL_ACT_7779797
CSNK2A2	6.18	IC50	660	nM	CHEMBL_ACT_12657927
CHRM1	6.13	IC50	748.7	nM	CHEMBL_ACT_7779791
SMN1	6.1	Potency	794.3	nM	CHEMBL_ACT_3884991
SLC47A2	6.08	IC50	830	nM	CHEMBL_ACT_12636212
ABCG2	6.04	IC50	903.8	nM	CHEMBL_ACT_18918287
BTK	6	IC50	1000	nM	CHEMBL_ACT_12657928
NPY1R	6	AC50	1000	nM	CHEMBL_ACT_25186748
Q63470	5.9	AC50	1248	nM	CHEMBL_ACT_6999789
FYN	5.9	IC50	1258	nM	CHEMBL_ACT_7747753
NAE1	5.89	EC50	1300	nM	CHEMBL_ACT_18372588
PTGS2	5.89	AC50	1300	nM	CHEMBL_ACT_25166431
ABCB1	5.82	IC50	1501	nM	CHEMBL_ACT_18918289
P12530	5.75	IC50	1785	nM	CHEMBL_ACT_7779781

Target pathways

Aggregated over 1 target gene(s): TOP2A.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Transcription of E2F targets under negative control by DREAM complex	1	TOP2A
SUMOylation of DNA replication proteins	1	TOP2A

Dominant GO biological processes

GO term	Targets
resolution of meiotic recombination intermediates	1
sister chromatid segregation	1
hematopoietic progenitor cell differentiation	1
DNA topological change	1
chromatin organization	1
DNA damage response	1
chromosome segregation	1
female meiotic nuclear division	1
apoptotic chromosome condensation	1
embryonic cleavage	1
regulation of circadian rhythm	1
positive regulation of apoptotic process	1
positive regulation of single stranded viral RNA replication via double stranded DNA intermediate	1
positive regulation of transcription by RNA polymerase II	1
rhythmic process	1

Indications & clinical

Indications

28 indications (2 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
neoplasm	4	MONDO:0005070	EFO:0000616
acute myeloid leukemia	3	MONDO:0018874	EFO:0000222
diffuse large B-cell lymphoma	3	MONDO:0018905	EFO:0000403
lymphoid leukemia	3	MONDO:0005402	EFO:0004289
multiple sclerosis	3	MONDO:0005301	MONDO:0005301
B-cell chronic lymphocytic leukemia	3	MONDO:0004948	EFO:0000095
metastatic prostate carcinoma	3	MONDO:0004956	EFO:0000196
acute lymphoblastic leukemia	3	MONDO:0004967	EFO:0000220
acute promyelocytic leukemia	3	MONDO:0012883	EFO:0000224
leukemia	3	MONDO:0005059	EFO:0000565
prostate adenocarcinoma	3	MONDO:0005082	EFO:0000673
prostate carcinoma	3	MONDO:0005159	EFO:0001663
secondary progressive multiple sclerosis	3	MONDO:0000450	EFO:0008522
follicular lymphoma	3	MONDO:0018906	MONDO:0018906
mantle cell lymphoma	2	MONDO:0018876	EFO:1001469
lymphoma	2	MONDO:0005062	EFO:0000574
myelodysplastic syndrome	2	MONDO:0018881	EFO:0000198
relapsing-remitting multiple sclerosis	2	MONDO:0005314	EFO:0003929
non-Hodgkin lymphoma	2	MONDO:0018908	EFO:0005952
acute biphenotypic leukemia	2	MONDO:0020322	MONDO:0019460
central nervous system cancer	1	MONDO:0002714	EFO:0000326
peripheral T-cell lymphoma, not otherwise specified	1	MONDO:0004964	EFO:0000211
angioimmunoblastic T-cell lymphoma	1	MONDO:0004977	EFO:0000255
chronic myeloid leukemia	1	MONDO:0011996	EFO:0000339
precursor T-cell acute lymphoblastic leukemia	1	MONDO:0020512	EFO:1001830

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

Clinical trials

Total trials: 178.

Phase distribution

Phase	Trials
PHASE2	77
PHASE1	32
PHASE3	24
PHASE1/PHASE2	21
PHASE4	11
Not specified	10
PHASE2/PHASE3	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07354698	PHASE4	NOT_YET_RECRUITING	Application of Mitoxantrone Hydrochloride Injection in Transoral Robotic Thyroid Cancer Surgery
NCT00180102	PHASE4	COMPLETED	AML2003 - Standard-Therapy vs Intensified Therapy for Adult Acute Myeloid Leukemia Patients <= 60 Years
NCT00180128	PHASE4	UNKNOWN	AIDA2000 - Risk-Adapted Therapy for Patients With Acute Promyelocytic Leukemia
NCT00199069	PHASE4	COMPLETED	German Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (05/93)
NCT00304291	PHASE4	COMPLETED	A Pilot Study of Mitoxantrone for the Treatment of Recurrent Neuromyelitis Optica (Devic’s Disease)
NCT00408278	PHASE4	COMPLETED	Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005)
NCT00526305	PHASE4	COMPLETED	LAL-Ph-2000: Treatment of Acute Lymphoblastic Leukemia Chromosome Philadelphia Positive
NCT00853008	PHASE4	COMPLETED	Treatment of High Risk Adult Acute Lymphoblastic Leukemia
NCT02021825	PHASE4	UNKNOWN	Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders
NCT02200978	PHASE4	COMPLETED	A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT02101853	PHASE3	ACTIVE_NOT_RECRUITING	Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
NCT02724163	PHASE3	RECRUITING	International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia
NCT03182244	PHASE3	ACTIVE_NOT_RECRUITING	A Study of ASP2215 Versus Salvage Chemotherapy In Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase 3 (FLT3) Mutation
NCT04668690	PHASE3	ACTIVE_NOT_RECRUITING	Clinical Study of Mitoxantrone Hydrochloride Liposome Injection vs. Chidamide in Patients With Relapsed/Refractory PTCL
NCT05717764	PHASE3	NOT_YET_RECRUITING	Clinical Study of Mitoxantrone Hydrochloride Liposome Injection Combined With Capecitabine Versus Capecitabine Monotherapy in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma Who Failed Platinum-containing Treatment
NCT07486479	PHASE3	NOT_YET_RECRUITING	Venetoclax, Azacitidine, and Mitoxantrone Hydrochloride Liposome Versus Idarubicin and Cytarabine in Newly Diagnosed AML
NCT00002835	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Lymphoma
NCT00004001	PHASE3	COMPLETED	S9916, Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy
NCT00136084	PHASE3	COMPLETED	Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00146159	PHASE3	TERMINATED	Study Evaluating Mitoxantrone in Multiple Sclerosis
NCT00151255	PHASE3	COMPLETED	All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT00416910	PHASE3	TERMINATED	Combination Chemotherapy With or Without G-CSF in Treating Patients With Relapsed Chronic Lymphocytic Leukemia
NCT00417079	PHASE3	COMPLETED	XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer
NCT00436839	PHASE3	COMPLETED	Taxotere Prostate Cancer New Indication Registration Trial in China
NCT00499018	PHASE3	UNKNOWN	Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma
NCT00562965	PHASE3	TERMINATED	Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator’s Choice In Follicular Non-Hodgkin’s Lymphoma (NHL)
NCT01382147	PHASE3	COMPLETED	Evaluation of Dose-dense Therapy by S-HAM in Comparison to Conventionally Timed Double Induction in Patients With Acute Myeloid Leukemia (AML)
NCT01522443	PHASE3	TERMINATED	Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer
NCT01564784	PHASE3	COMPLETED	A Study Of Inotuzumab Ozogamicin Versus Investigator’s Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia
NCT02688140	PHASE3	COMPLETED	Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia
NCT02937285	PHASE3	COMPLETED	National Multicenter, Controlled, Single-blind Study With Two Parallel Groups Evaluating the Safety and Efficacy of Sequential Treatment With Mitoxantrone and Interferon Versus Interferon Alone in Patients With Strong Risk of Progression in the Initial Phase of Multiple Sclerosis
NCT03250338	PHASE3	COMPLETED	Study Investigating the Efficacy of Crenolanib With Chemotherapy vs Chemotherapy Alone in R/R FLT3 Mutated AML
NCT03504410	PHASE3	TERMINATED	Efficacy/Safety of CPI-613 in Combination With HD Cyt. and Mito. vs HD Cyt. and Mito. in Older Patients With R/R AML
NCT03926624	PHASE3	TERMINATED	Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd/4th Salvage
NCT05313958	PHASE2/PHASE3	UNKNOWN	Treateament of Newly Diagnosed Acute Monocytic Leukemia in Children
NCT05739630	PHASE2/PHASE3	UNKNOWN	M-PTCy vs BuCy in Haploidentical HSCT for Acute Leukemia
NCT02553460	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I
NCT03164057	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT03591510	PHASE2	ACTIVE_NOT_RECRUITING	A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 24 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

27 molecules share ≥1 primary target. Top 27 by shared-target count:

Molecule	Source	Status	Shared targets
AMSACRINE	ChEMBL	Phase 4 (approved)	TOP2A
CIPROFLOXACIN	ChEMBL	Phase 4 (approved)	TOP2A
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	TOP2A
DEXRAZOXANE	ChEMBL	Phase 4 (approved)	TOP2A
DOXORUBICIN	ChEMBL	Phase 4 (approved)	TOP2A
EPIRUBICIN	ChEMBL	Phase 4 (approved)	TOP2A
ETOPOSIDE	ChEMBL	Phase 4 (approved)	TOP2A
IDARUBICIN	ChEMBL	Phase 4 (approved)	TOP2A
TENIPOSIDE	ChEMBL	Phase 4 (approved)	TOP2A
TOPOTECAN	ChEMBL	Phase 4 (approved)	TOP2A
CURCUMIN	ChEMBL	Phase 3	TOP2A
GEPOTIDACIN	ChEMBL	Phase 3	TOP2A
AXL-1717	ChEMBL	Phase 2	TOP2A
DECERNOTINIB	ChEMBL	Phase 2	TOP2A
LOSOXANTRONE	ChEMBL	Phase 2	TOP2A
NEMORUBICIN	ChEMBL	Phase 2	TOP2A
PIROXANTRONE	ChEMBL	Phase 2	TOP2A
Afatinib	PubChem	Approved	TOP2A
Binimetinib	PubChem	Approved	TOP2A
Crizotinib	PubChem	Approved	TOP2A
Gefitinib	PubChem	Approved	TOP2A
Idelalisib	PubChem	Approved	TOP2A
Pazopanib	PubChem	Approved	TOP2A
podofilox	PubChem	Approved	TOP2A
regorafenib	PubChem	Approved	TOP2A
Selumetinib	PubChem	Approved	TOP2A
Trametinib	PubChem	Approved	TOP2A