General
Preferred name
DEFLAZACORT
Synonyms
MDL 458 ()
Calcort ()
MDL458 ()
Emflaza ()
Zamene ()
MDL-458 ()
P&D ID
PD012694
CAS
14484-47-0
74712-90-6
Tags
prodrug
natural product
drug
available
Approved by
FDA
First approval
2017
Drug Status
investigational
approved
Drug indication
Anti-Inflammatory
Duchenne dystrophy
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE The half-life of deflazacort ranges from 1.1 to 1.9 h [A18725,L6703]
PHARMACODYNAMICS Deflazacort exerts anti-inflammatory activity in DMD, likely improving various symptoms, including muscle weakness and cardiorespiratory symptoms in addition to delaying their onset.[A179455] This allows for an increased quality of life and prevents the necessity for surgical procedures, such as those for scoliosis, which is associated with DMD. Studies showed significant preservation of muscle mass in patients generally treated with 0.9 mg/kg/day of deflazacort compared to a control group. The following findings are based on clinical studies using deflazacort on a long term basis[A179455,A179458]:; ; **Effects on muscle strength** ; ; At age 16, individuals treated with long-term deflazacort had 63 ± 4% score in muscle strength compared to a mean muscle strength score of 31 ± 3% for control patients[A179455]. Significant improvements in climbing stairs and rising from a supine position were also seen in patients taking deflazacort.[A179455] ; ; **Effects on ambulation**; ; Ambulation was significantly higher by 12 years of age and 18 years of age in patients taking deflazacort when compared with the control group. The control group showed a mean loss of ambulation of 2 years sooner than with deflazacort treatment.[A179458] ; ; **Effects on cardiac function**; ; Mean left ventricular ejection fraction (a measure of cardiac function) was higher in patients treated with deflazacort over the long term. Preservation of cardiac function was demonstrated by a mean difference in ejection fraction of about 7%, favoring study groups taking deflazacort over control groups.[A179458]; ; **Effects on spinal alignment**; ; Children treated with deflazacort also significantly lowered the rate and severity of scoliosis and eliminated the need for scoliosis surgery after long-term treatment.[A179455,A179458]
MOA Deflazacort is a corticosteroid prodrug with an active metabolite, 21-deflazacort, which binds to the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects on the body.[A18725,A179461,A179464] The exact mechanism by which deflazacort exerts its therapeutic effects in patients with DMD is unknown but likely occurs via its anti-inflammatory activities.[FDA label]
ROE Urinary excretion is the major route of deflazacort elimination, accounting for about about 70% of the excreted dose.[A18725] The remainder of the dose (about 30%) is excreted in the feces[A18725]. Elimination is almost completed by 24 hours post-dose.[A179467] 21-deflazacort makes up about 18% of the eliminated drug in the urine.[FDA label]
INDICATION Deflazacort is indicated for the treatment of Duchenne Muscular Dystrophy (DMD) in patients 2 years of age and older.[FDA label]
TOXICITY The LD50 for the oral dose is 5200 mg/kg (mouse); Oral TDLO (woman): 0.12 mg/kg[MSDS]; ; **A note on altered endocrine function and immunosuppression**; ; Deflazacort, as a steroid prodrug used over a long-term period, can cause hormone imbalance leading to diseases such as Cushing's Syndrome and hypothalamic-pituitary-adrenal axis suppression. It can also predispose to infection, as it promotes immunosuppression.[A179464] It is important to monitor for hormonal imbalance and infection and provide necessary treatment if they occur.[FDA label]; ; **Mutagenicity/carcinogenicity**; ; Mutagenicity assays were negative in various laboratory and in vivo assays performed on rats.[FDA label,L6703] Chronic use in mice for 2 years in one study resulted in a higher rate of osteoma and osteosarcomas in mice receiving 0.06, 0.12, 0.25, 0.50, or 1.0 mg/kg of deflazacort daily.[FDA label]; ; **Use in pregnancy**; ; There are no sufficient data to support the administration of deflazacort during pregnancy. Corticosteroid drugs such as deflazacort should only be used during pregnancy only if the benefits of therapy outweigh the potential risks.[FDA label,L6703]; ; **Use in lactation**; ; Corticosteroids, when administered systemically, are excreted in the breastmilk. Exposure may lead to disturbances in bone development and growth and endocrine disturbances in the exposed infant.[FDA label,L6703]; ;
METABOLISM After oral ingestion, deflazacort is deacetylated at position 21 by plasma esterases, producing the active metabolite 21-deflazacort.[A18725,A179464,FDA label,L6703] 21-deflazacort is then further metabolized by CYP3A4 to inactive metabolite products.[FDA label,A179473] Deflazacort 21-OH metabolism is extensive. The metabolite of deflazacort-21-OH is deflazacort 6-beta-OH.[A179473,L6703]
ABSORPTION Deflazacort is rapidly absorbed after oral administration with peak concentration occurring within 1-2 hours.[A179464,FDA label] One pharmacokinetic study determined an AUC (area under the curve) of 280 ng/ml · h.[A18725]; ; The bioavailability of both the oral suspension and tablet are similar.[FDA label] In clinical studies, coadministration of deflazacort crushed with food or applesauce did not affect absorption or bioavailability.[FDA label];
DESCRIPTION Deflazacort is a derivative glucocorticoid that is used as an anti-inflammatory and immunosuppressant. It is a prodrug that is metabolised to the active form, 21-desacetyl deflazacort (PubChem CID 97547130) . (GtoPdb)
Compound Sets
15
Cayman Chemical Bioactives
20386
ChEMBL Approved Drugs
CHEMBL1201891
ChEMBL Drugs
CHEMBL1201891
Drug Repurposing Hub
DrugBank
DB11921
DrugBank Approved Drugs
DB11921
DrugCentral
793
DrugCentral Approved Drugs
793
DrugMAP
DMV0RNS
DrugMAP Approved Drugs
DMV0RNS
Guide to Pharmacology
9477
MedChem Express Bioactive Compound Library
HY-13609
Prestwick Chemical Library
Selleckchem Bioactive Compound Library
Deflazacor
TargetMol Bioactive Compound Library
T0485
External IDs
31
Properties
(calculated by RDKit )
Molecular Weight
441.22
Hydrogen Bond Acceptors
7
Hydrogen Bond Donors
1
Rotatable Bonds
3
Ring Count
5
Aromatic Ring Count
0
cLogP
2.56
TPSA
102.26
Fraction CSP3
0.68
Chiral centers
8.0
Largest ring
6.0
QED
0.68
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Metabolism
Immunology/Inflammation
Vitamin D Related/Nuclear Receptor
Target
Glucocorticoid Receptor
NR3C1
Indication
joint inflammation
MOA
Glucocorticoid Receptor agonist
Source data