Mitotane

Summary

Mitotane (CHEMBL1670) is an approved small molecule (ATC L01XX23) targeting CYP11A1; indicated across 5 conditions including neoplasm and adrenal cortex carcinoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01XX23
• Targets: 1 (CYP11A1)
• Indications: 5 conditions
• Clinical trials: 9
• Chemistry: 320 Da · C14H10Cl4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1670
Name	Mitotane
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4211
ATC	L01XX23
Molecular formula	C14H10Cl4
Molecular weight	320
InChIKey	JWBOIMRXGHLCPP-UHFFFAOYSA-N

SMILES: C1=CC=C(C(=C1)C(C2=CC=C(C=C2)Cl)C(Cl)Cl)Cl

IUPAC name: 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene

Also known as: CB 313, CB-313, Chloditan, Chlodithane, Lysodren, Mitotan, Mitotane, Mitotano, NSC-38721, O, p’-ddd, o p’-tde

Patent coverage: 19,503 distinct patent families (83,856 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 82,897 (99%) 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
CYP11A1	CYP11A1	Inhibition		0.2%	P05108

Broader ChEMBL bioactivity targets: 27 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Lethal(3)malignant brain tumor-like protein 1, Microtubule-associated protein tau, Lysine-specific demethylase 4E, Prelamin-A/C, RecQ-like DNA helicase BLM, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Thyrotropin receptor, Glucocorticoid receptor.

Bioactivity

ChEMBL activities: 24 potent at pChembl ≥ 5 of 40 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BLM	7.65	Potency	22.4	nM	CHEMBL_ACT_4750011
BLM	7.65	Potency	22.4	nM	CHEMBL_ACT_4937922
PGR	6.35	AC50	450	nM	CHEMBL_ACT_25223524
HTR6	6.19	Ki	651	nM	CHEMBL_ACT_7777636
SLC6A3	6.1	Ki	795	nM	CHEMBL_ACT_7775512
SLC6A2	6.09	IC50	819	nM	CHEMBL_ACT_7775447
SLC6A2	6.09	Ki	812	nM	CHEMBL_ACT_7775448
P15207	6	AC50	1000	nM	CHEMBL_ACT_25187781
SLC6A3	6	IC50	1001	nM	CHEMBL_ACT_7775511
ACAT1	5.89	IC50	1300	nM	CHEMBL_ACT_25878338
NR3C1	5.85	AC50	1400	nM	CHEMBL_ACT_25176410
HTR6	5.85	IC50	1402	nM	CHEMBL_ACT_7777635
SLC6A4	5.8	Ki	1601	nM	CHEMBL_ACT_7777638
ADRA2A	5.56	Ki	2755	nM	CHEMBL_ACT_7773453
SLC6A4	5.52	IC50	3015	nM	CHEMBL_ACT_7777637
HTR2B	5.51	Ki	3075	nM	CHEMBL_ACT_7777628
ADORA3	5.38	Ki	4208	nM	CHEMBL_ACT_7773443
HTR2B	5.32	IC50	4832	nM	CHEMBL_ACT_7777627
MAPT	5.3	Potency	5012	nM	CHEMBL_ACT_4044382
LMNA	5.2	Potency	6310	nM	CHEMBL_ACT_3664230
MAPT	5.2	Potency	6310	nM	CHEMBL_ACT_3973871
ADORA3	5.13	IC50	7445	nM	CHEMBL_ACT_7773442
ADRA2A	5.13	IC50	7347	nM	CHEMBL_ACT_7773452
NR1I2	5.12	AC50	7500	nM	CHEMBL_ACT_25188625

Target pathways

Aggregated over 1 target gene(s): CYP11A1.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Pregnenolone biosynthesis	1	CYP11A1
Endogenous sterols	1	CYP11A1
Defective CYP11A1 causes AICSR	1	CYP11A1

Dominant GO biological processes

GO term	Targets
C21-steroid hormone biosynthetic process	1
glucocorticoid biosynthetic process	1
cholesterol metabolic process	1
sterol metabolic process	1
cortisol metabolic process	1
vitamin D metabolic process	1
cellular response to peptide hormone stimulus	1
steroid hormone biosynthetic process	1
alcohol metabolic process	1
lipid metabolic process	1
steroid biosynthetic process	1
steroid metabolic process	1
C21-steroid hormone metabolic process	1

Indications & clinical

Indications

5 indications (3 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
adrenal cortex carcinoma	4	MONDO:0006639	EFO:1000796
adrenal cortex neoplasm	4	MONDO:0036591	MONDO:0036591
carcinoma	3	MONDO:0004993	EFO:0000313

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

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE3	4
PHASE2	3
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03583710	PHASE3	RECRUITING	Mitotane With or Without Cisplatin and Etoposide After Surgery in Treating Patients With Stage I-III Adrenocortical Cancer With High Risk of Recurrence
NCT00094497	PHASE3	COMPLETED	Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT)
NCT00304070	PHASE3	COMPLETED	Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor
NCT00777244	PHASE3	UNKNOWN	Efficacy of Adjuvant Mitotane Treatment (ADIUVO)
NCT06831175	PHASE2	RECRUITING	Phase II Study of PD-1 Inhibitor Combined With Apatinib and Mitotane in the Treatment of Advanced Adrenal Cortical Carcinoma
NCT00778817	PHASE2	TERMINATED	IMC-A12 With Mitotane vs Mitotane Alone in Recurrent, Metastatic, or Primary ACC That Cannot Be Removed by Surgery
NCT05634577	PHASE2	TERMINATED	A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma
NCT02057237	PHASE1	COMPLETED	A Safety and Feasibility Study of Mitotane in Prostate Cancer
NCT05344027	Not specified	COMPLETED	The Impact of Mitotane Therapy on Serum Free Proteins in Patients With Adrenocortical Carcinoma

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 3 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.

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

Molecule	Source	Status	Shared targets
AMINOGLUTETHIMIDE	ChEMBL	Phase 4 (approved)	CYP11A1