Doxercalciferol

Summary

Doxercalciferol (CHEMBL1200810) is an approved small-molecule bone density conservation agent (ATC H05BX03) targeting VDR; indicated across 6 conditions including chronic kidney disease and parathyroid gland disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: H05BX03
• Targets: 1 (VDR)
• Indications: 6 conditions
• Clinical trials: 14
• Chemistry: 412.6 Da · C28H44O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1200810
Name	Doxercalciferol
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5281107
ChEBI	CHEBI:4712
ATC	H05BX03
Molecular formula	C28H44O2
Molecular weight	412.6
InChIKey	HKXBNHCUPKIYDM-CGMHZMFXSA-N

SMILES: C[C@H](/C=C/[C@H](C)C(C)C)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](C[C@@H](C3=C)O)O)C

IUPAC name: trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol

ChEBI definition: A hydroxy seco-steroid and synthetic vitamin D2 analogue that undergoes metabolic activation in vivo to form 1α,25-dihydroxyvitamin D2 (1α,25-(OH)2D2), a naturally occurring, biologically active form of vitamin D2. It is used to treat secondary hyperparathyroidism, a condition in which the body produces excess parathyroid hormone (PTH; a natural substance needed to control the amount of calcium in the blood) in certain people with chronic kidney disease.

Pharmacological roles (ChEBI): provitamin, bone density conservation agent, prohormone.

Also known as: 1.alpha.-hydroxyergocalciferol, 1.alpha.-hydroxyvitamin d2, Doxercalciferol, GZ427397, Hectorol, TSA-840, DOXERCALCIFEROL, SID144206531, doxercalciferol

Patent coverage: 324 distinct patent families (951 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
VDR	Vitamin D receptor	Agonist		0.2%	P11473

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Vitamin D3 receptor.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
VDR	6.02	EC50	960	nM	CHEMBL_ACT_26335901

Target pathways

Aggregated over 1 target gene(s): VDR.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Vitamin D (calciferol) metabolism	1	VDR
Nuclear Receptor transcription pathway	1	VDR
SUMOylation of intracellular receptors	1	VDR

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
cell morphogenesis	1
skeletal system development	1
calcium ion transport	1
intracellular calcium ion homeostasis	1
lactation	1
negative regulation of cell population proliferation	1
positive regulation of gene expression	1
negative regulation of keratinocyte proliferation	1
cell differentiation	1
positive regulation of bone mineralization	1
intracellular receptor signaling pathway	1
phosphate ion transmembrane transport	1
nuclear receptor-mediated bile acid signaling pathway	1
mRNA transcription by RNA polymerase II	1

Indications & clinical

Indications

3 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
chronic kidney disease	4	MONDO:0005300	EFO:0003884
parathyroid gland disorder	4	MONDO:0001223	EFO:0005754
secondary hyperparathyroidism	4	MONDO:0006964	EFO:1001173

2 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
psoriasis	2	MONDO:0005083	EFO:0000676
neoplasm	1	MONDO:0005070	EFO:0000616

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

Clinical trials

Total trials: 14.

Phase distribution

Phase	Trials
PHASE4	6
PHASE2	3
PHASE3	2
PHASE1	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00418600	PHASE4	COMPLETED	A Phase 4, Conversion Study of Hectorol® Injection to Hectorol® Capsules in Stage 5 CKD Patients on Dialysis
NCT00502268	PHASE4	WITHDRAWN	Vitamin D and Carboxy PTH Fragments in Coronary Calcification
NCT00528788	PHASE4	COMPLETED	How Vitamin D Analogues Affect Endothelial Cells in Patients on Dialysis
NCT00646282	PHASE4	TERMINATED	Mineral Metabolism and Vascular Effects of Vitamin D Therapy in Kidney Transplant Patients
NCT00749736	PHASE4	COMPLETED	The Role of Vitamin D in Immune Function in Patients With Chronic Kidney Disease (CKD) Stages 3 and 4.
NCT00889629	PHASE4	COMPLETED	Pilot Study Evaluating Doxercalciferol Replacement Therapy in Kidney Transplant Recipients
NCT02282813	PHASE3	COMPLETED	Extension Study of CTAP101-CL-3001 or CTAP101-CL-3002
NCT02859896	PHASE3	TERMINATED	Safety and Efficacy of Hectorol in Pediatric Patients With Chronic Kidney Disease Stage 3 and 4 With Secondary Hyperparathyroidism Not Yet on Dialysis
NCT00022412	PHASE2	COMPLETED	Doxercalciferol Before Surgery in Treating Localized Prostate Cancer
NCT00052832	PHASE2	COMPLETED	Doxercalciferol in Treating Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
NCT00601107	PHASE2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of Doxercalciferol Capsules in Participants With Moderate to Severe Psoriasis
NCT00511017	PHASE1	TERMINATED	Doxercalciferol in Recurrent Pediatric Solid Tumors
NCT00792857	PHASE1	COMPLETED	Comparison of I.V. CTAP201 and Doxercalciferol (Hectorol) in Subjects With Chronic Kidney Disease (CKD) and Secondary Hyperparathyroidism (SHPT)
NCT00285467	Not specified	COMPLETED	Cholecalciferol Versus Doxercalciferol in the Treatment of Secondary Hyperparathyroidism in Chronic Kidney 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.

9 molecules share ≥1 primary target. Top 9 by shared-target count:

Molecule	Source	Status	Shared targets
CALCIPOTRIENE	ChEMBL	Phase 4 (approved)	VDR
CALCITRIOL	ChEMBL	Phase 4 (approved)	VDR
CHOLECALCIFEROL	ChEMBL	Phase 4 (approved)	VDR
TACALCITOL	ChEMBL	Phase 4 (approved)	VDR
CURCUMIN	ChEMBL	Phase 3	VDR
MAXACALCITOL	ChEMBL	Phase 3	VDR
SEOCALCITOL	ChEMBL	Phase 3	VDR
TAUROLITHOCHOLIC ACID	ChEMBL	Phase 3	VDR
chenodiol	PubChem	Approved	VDR