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Protein / target

Cholesterol side-chain cleavage enzyme, mitochondrial

Encoded byCYP11A1P05108Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Cholesterol monooxygenase (side-chain-cleaving)

Strongest disease association

Adrenal Hyperplasia, Congenital

Via encoding gene CYP11A1 · Genetic evidence · score 0.55

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones.

View complete UniProt function annotation

A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:21636783). Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal (PubMed:21636783). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:21636783)

Subcellular location

Mitochondrion inner membrane
Domains and Gene Ontology detail (14)

Gene Ontology

  • Cmitochondrial inner membrane
  • Cmitochondrial matrix
  • Cmitochondrion
  • Fcholesterol monooxygenase (side-chain-cleaving) activity
  • Fheme binding
  • Firon ion binding
  • PC21-steroid hormone biosynthetic process
  • Pcellular response to peptide hormone stimulus
  • Pcholesterol metabolic process
  • Pcortisol metabolic process
  • Pglucocorticoid biosynthetic process
  • Psteroid hormone biosynthetic process

521 aa · 60 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage…
  • ·cholesterol monooxygenase (side-chain-cleaving) activity
  • ·cholesterol metabolic process
  • ·sterol metabolic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

2 medicines · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Adrenal Cortex Neoplasms1 medicine
Cushing's Syndrome1 medicine
Broader indication categories (1)
Neoplasms1 medicine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

3 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

mitotane
Narrow target profileApprovedInhibitor

Cytochrome P450 11A1 inhibitor

Indicated for Adrenal Cortex Neoplasms, Neoplasms

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

ketoconazole
Inhibitor

Cytochrome P450 11A1 inhibitor

Indicated for Cushing's Syndrome

Direct interaction with this protein · 1 of 4 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CYP11A1

Gene-level evidence surfaced through the gene CYP11A1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Adrenal Hyperplasia, Congenital
0.74Moderately supported

Genetic evidence dominant · Open Targets 0.46

Cushing's Syndrome
0.64Moderately supported

Clinical evidence dominant · Open Targets 0.49

Neoplasms
0.62Moderately supported

Clinical evidence dominant · Open Targets 0.49

Adrenal Cortex Neoplasms
0.46Limited support

Clinical evidence dominant · Open Targets 0.37

View evidence synthesis (4)
Adrenal Hyperplasia, CongenitalModerately supported
0.74
agreement 0.640.85
Genetic52%Pathway23%Animal model21%Literature4%

Open Targets aggregate 0.46 · 4 independent evidence families

Cushing's SyndromeModerately supported
0.64
agreement 0.510.77
Clinical84%Animal model14%Literature2%

Open Targets aggregate 0.49 · 3 independent evidence families

NeoplasmsModerately supported
0.62
agreement 0.470.78
Clinical82%Literature18%

Open Targets aggregate 0.49 · 2 independent evidence families

Adrenal Cortex NeoplasmsLimited support
0.46
agreement 0.310.62
Clinical97%Literature3%

Open Targets aggregate 0.37 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Cushing's Syndrome0.49
Neoplasms0.49
Adrenal Hyperplasia, Congenital0.46
Adrenal Cortex Neoplasms0.37

Drug development

3 compounds recorded · 3 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (3)
LEVOKETOCONAZOLEApproval
AMINOGLUTETHIMIDEApproval
MITOTANEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
SM · Approved DrugSM · Structure with LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high conf

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ACTIVE_NOT_RECRUITING · via ketoconazole · NCT07585851

COMPLETED · via ketoconazole · NCT00000579

WITHDRAWN · via ketoconazole · NCT02147964

ClinicalTrials.gov via the drug-target graph.

What's happening now

3

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Accelerated approval granted2014-11-18

    Accelerated approval: Ketoconazole Esteve (previously Ketoconazole HRA) (EMA)

    ema · regulatory · ema · via ketoconazole

  2. New publication2012-09-01
    Effect of ketoconazole on the pharmacokinetic profile of buprenorphine following administration of a once-weekly buprenorphine transdermal system.

    Clinical drug investigation · 2012 · 21 citations · Europe PMC · via ketoconazole

  3. Regulatory approval2004-04-28

    Approval: Lysodren (EMA)

    ema · regulatory · ema · via mitotane

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.