Drotrecogin Alfa (Activated)

Summary

Drotrecogin Alfa (Activated) (CHEMBL2109065) is an approved protein (ATC B01AD10) targeting F5 and F8; indicated across 10 conditions including thrombotic disease and multiple organ dysfunction syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Protein
• ATC class: B01AD10
• Targets: 2 (F5, F8)
• Indications: 10 conditions
• Clinical trials: 16

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2109065
Name	Drotrecogin Alfa (Activated)
Type	Protein
Max phase	4
ATC	B01AD10

Also known as: Activated protein c, Drotrecogin alfa, Drotrecogin alfa (activated), Drotrecogin alfa activated, activated, Drotrecogin-alfa, Drotrecogina alfa (activada), Drotrecogine alfa (active), LY-203638, LY203638, Xigris, DROTRECOGIN ALFA (ACTIVATED)

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
F5	coagulation factor V	Inhibition		0.2%	P12259
F8	coagulation factor VIII	Inhibition		0%	P00451

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 2 target gene(s): F5, F8.

Top Reactome pathways

22 total, by targets touching each:

Pathway	Targets	Genes
Platelet degranulation	2	F5, F8
R-HSA-140875	2	F5, F8
COPII-mediated vesicle transport	2	F5, F8
Cargo concentration in the ER	2	F5, F8
Initiation of coagulation cascade	2	F5, F8
Regulation of clotting cascade	2	F5, F8
Amplification and propagation of coagulation cascade	2	F5, F8
R-HSA-140837	1	F8
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1	F8
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	F5
Post-translational protein phosphorylation	1	F5
Defective factor IX causes thrombophilia	1	F8
Defective F8 accelerates dissociation of the A2 domain	1	F8
Defective F8 cleavage by thrombin	1	F8
Defective F8 binding to von Willebrand factor	1	F8
Defective F8 binding to the cell membrane	1	F8
Defective cofactor function of FVIIIa variant	1	F8
Defective F8 secretion	1	F8
Defective F9 variant does not activate FX	1	F8
Defective F8 sulfation at Y1699	1	F8
Defective cleavage of FV variant at a.a.534	1	F5
Defective cleavage of FV variant at R334	1	F5

Dominant GO biological processes

GO term	Targets
blood coagulation	2
hemostasis	2
blood circulation	1
response to vitamin K	1
acute-phase response	1
blood coagulation, intrinsic pathway	1

Indications & clinical

Indications

10 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
thrombotic disease	4	MONDO:0000831	HP:0004419
multiple organ dysfunction syndrome	4	MONDO:0043726	EFO:1001373
toxic shock syndrome	3	MONDO:0001881	EFO:0006834
hypotensive disorder	3	MONDO:0005468	EFO:0005251
chronic kidney disease	2	MONDO:0005300	EFO:0003884
pulmonary embolism	2	MONDO:0005279	EFO:0003827
stroke disorder	2	MONDO:0005098	EFO:0000712
adult acute respiratory distress syndrome	2	MONDO:0100130	MONDO:0100130

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

Clinical trials

Total trials: 16.

Phase distribution

Phase	Trials
PHASE4	6
PHASE2	5
PHASE3	4
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00045760	PHASE4	COMPLETED	The Study of Drotrecogin Alfa (Activated) in a Subpopulation of Adult Patients With Severe Sepsis
NCT00049777	PHASE4	COMPLETED	A Trial of Heparin in Patients With Severe Sepsis Who Are Undergoing Treatment With Drotrecogin Alfa (Activated)
NCT00067730	PHASE4	COMPLETED	A Safety Evaluation of Drotrecogin Alfa (Activated) in Patients With Blood Cancer, Severe Infection Related to Bone Marrow Transplantation
NCT00279214	PHASE4	COMPLETED	Hemodynamic and Perfusion Response to Drotrecogin Alfa (Activated) in Patients With Septic Shock
NCT00568893	PHASE4	COMPLETED	An Open Label Study of Severe Sepsis in Adults
NCT01017107	PHASE4	COMPLETED	Activated Protein C in Severe Acute Pancreatitis
NCT00049764	PHASE3	COMPLETED	Investigation of the Efficacy and Safety of Drotrecogin Alfa (Activated) in Pediatric Severe Sepsis
NCT00190788	PHASE3	COMPLETED	Extended Therapy of Drotrecogin Alfa (Activated) 4 vs 7 Days Infusion
NCT00568737	PHASE3	COMPLETED	The Study of Drotrecogin Alfa (Activated) in Adult Patients With Severe Sepsis at a Low Risk of Death
NCT00604214	PHASE3	COMPLETED	Efficacy and Safety of Drotrecogin Alfa (Activated) in Adult Patients With Septic Shock
NCT00112164	PHASE2	TERMINATED	Activated Protein C to Treat Acute Lung Injuries
NCT00191724	PHASE2	COMPLETED	Adjuvant Treatment of Pulmonary Embolism With Drotrecogin Alfa (Activated): Phase II Exploratory Study
NCT00386425	PHASE2	COMPLETED	Evaluate Protein C Levels in Severe Sepsis Patients on Drotrecogin Alfa (Activated)
NCT00533546	PHASE2	TERMINATED	Activated Protein C in Acute Stroke Trial
NCT01411670	PHASE2	COMPLETED	Administration of Human Protein C Concentrates in Patients With Sepsis and Septic Shock.
NCT02843685	Not specified	COMPLETED	Regression Discontinuity Design to Evaluate of Drotrecogin Alpha Effectiveness

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.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

Molecule	Source	Status	Shared targets
EDOXABAN	ChEMBL + PubChem	Phase 4 (approved)	F5
RAZAXABAN	ChEMBL	Phase 2	F5