Drugs in the medical treatment of Cushing's syndrome – an update on mifepristone and pasireotide

Figures & data

Table 1. Drugs under development for treatment of Cushing's syndrome.

Compound	Company	Structure	Indication	Stage of development	Class
Mifepristone (Corlux)	Corcept Therapeutics	Butanoic acid,4-[[1-[[(4 aminobutyl)amino]carbonyl]-3-methylbutyl]amino]-4	Psychotic major depression, Cushing's syndrome	Completed Phase III clinical trial in Cushing's disease Received FDA approval	GCR type II antagonist
Mifepristone (Mifedren)	HRA Pharma	Estra-4,9-dien-one,11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)-, (11β,17β) [CAS 84371-65-3]	Cushing's syndrome	Phase III clinical trial	GCR antagonist
Pasireotide	Novartis	Cyclo[(4R)-4-(2-aminoethylcarbamoyloxy)-l-propyl-l-phenylglycyl-d-tryptophyl-l-lysyl-4-o-benzyl-l-tyrosyl-l-phenylalanyl-]	Acromegaly, carcinoid tumors, Cushing's syndrome	Completed Phase III clinical trial	sst receptor agonist with binding ability to sst1, sst2, sst3 and sst5 receptors
Dopastatin	Ipsen	A chimeric molecule; specific structure not available	Acromegaly, hyperprolactinemia, Cushing's disease	Preclinical studies on pituitary tumors.Phase II clinical trial for acromegaly	Combined sst and D2 receptor agonist

D₂: Dopamine; GCR: Glucocorticoid receptor; sst: Somatostatin.

Table 2. Drug treatment of Cushing's syndrome.

Drug	Main mechanism of drug action
Ketoconazole	↓ 17-hydroxylase, 11β-hydroxylase, cholesterol SCC
Metyrapone	↓ 11β-hydroxylase
Mitotane	Formation of acyl chloride, binding to bionucleophiles
Etomidate	↓ 11β-hydroxylase
Cabergoline	D2 agonist
sst analogs	sst receptor agonists
Glitazones	PPAR-γ agonists
Mifepristone	Type II GCR antagonist

D₂: Dopamine; GCR: Glucocorticoid receptor; PPAR: Peroxisome proliferator-activated receptor; SCC: Side-chain cleavage; sst: Somatostatin.