Thyrotropin Alfa

Identification

Name
Thyrotropin Alfa
Accession Number
DB00024  (BTD00020, BIOD00020)
Type
Biotech
Groups
Approved, Vet Approved
Biologic Classification
Protein Based Therapies
Hormones
Description

Thyrotropin alfa is a recombinant form of thyroid stimulating hormone used in performing certain tests in patients who have or have had thyroid cancer. It is also used along with a radioactive agent to destroy remaining thyroid tissue in certain patients who have had their thyroid gland removed because of thyroid cancer. It is a heterodimeric glycoprotein comprised of two non-covalently linked subunits, an alpha subunit of 92 amino acid residues containing two N-linked glycosylation sites and a beta subunit of 112 residues containing one N-linked glycosylation site. The alpha subunit is nearly identical to that of human chorionic gonadotropin (hCG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The alpha subunit is thought to be the effector region responsible for stimulation of adenylate cyclase (involved the generation of cAMP). The beta subunit (TSHB) is unique to TSH, and therefore determines its receptor specificity. The amino acid sequence of thyrotropin alfa is identical to that of human pituitary thyroid stimulating hormone.

Protein structure
Db00024
Protein chemical formula
C975H1513N267O304S26
Protein average weight
22672.9 Da
Sequences
>Alpha chain
APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCC
VAKSYNRVTVMGGFKVENHTACHCSTCYYHKS
>Beta chain
FCIPTEYTMHIERRECAYCLTINTTICAGYCMTRDINGKLFLPKYALSQDVCTYRDFIYR
TVEIPGCPLHVAPYFSYPVALSCKCGKCNTDYSDCIHEAIKTNYCTKPQKSY
Download FASTA Format
Synonyms
  • rTSH
  • Thyroid stimulating hormone
  • Thyrotrophin-alfa
  • Thyrotrophin-alpha
  • Thyrotropin
  • Thyrotropin-a
  • Thyrotropin-alpha
  • Thytrophin
  • TSH
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ThyrogenPowder, for solution0.9 mgIntramuscularSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2002-08-12Not applicableCanada
ThyrogenInjection, powder, for solution.9 mg/mLIntramuscularGenzyme Corporation1998-11-30Not applicableUs
ThyrogenKitGenzyme Corporation1998-11-30Not applicableUs
Categories
UNII
AVX3D5A4LM
CAS number
194100-83-9

Pharmacology

Indication

For detection of residueal or recurrent thyroid cancer

Structured Indications
Pharmacodynamics

Binding of thyrotropin alfa to TSH receptors on normal thyroid epithelial cells or on well-differentiated thyroid cancer tissue stimulates iodine uptake and organification. Thyrogen is an exogenous source of human TSH that offers an additional diagnostic tool in the follow-up of patients with a history of well-differentiated thyroid cancer.

Mechanism of action

Thyrotropin Alfa binds to the thyrotropin receptors found on any residual thyroid cells or tissues. This stimulates radioactive iodine uptake for better radiodiagnostic imaging.

TargetActionsOrganism
AThyrotropin receptor
agonist
Human
Absorption

Time to peak: Median: 10 hours (range: 3-24 hours) After a single intramuscular injection of 0.9 mg of thyrotropin alfa: Cmax= 116+38mU/L, Tmax=22+8.5 hours. AUC=5088+1728 mU·hr/L.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

kidney and liver

Half life

25 ± 10 hours

Clearance
Not Available
Toxicity

No difference in efficacy and toxicity between adult and geriatric patients. No studies in lactating women, pregnant women and pediatrics. Cautionary administration is advised.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference

19366632

General References
Not Available
External Links
UniProt
P01225
Genbank
M16647
ChEMBL
CHEMBL1201533
Therapeutic Targets Database
DAP001248
PharmGKB
PA164746560
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
ATC Codes
H01AB01 — Thyrotropin alfaV04CJ01 — Thyrotropin
AHFS Codes
  • 36:60.00 — Thyroid Function
FDA label
Download (2.27 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingDiagnosticDifferentiated Thyroid Cancer (DTC)1
2CompletedTreatmentBenign Nontoxic and Toxic Goiter / Graves' Disease1
2CompletedTreatmentGoiter, Nodular1
2CompletedTreatmentRecurrent Thyroid Cancer / Stage IVA Follicular Thyroid Cancer / Stage IVA Papillary Thyroid Cancer / Stage IVB Follicular Thyroid Cancer / Stage IVB Papillary Thyroid Cancer / Stage IVC Follicular Thyroid Cancer / Stage IVC Papillary Thyroid Cancer1
3CompletedNot AvailableNeoplasms, Thyroid1
3CompletedTreatmentDifferentiated Thyroid Cancer (DTC)1
3RecruitingOtherLow Risk Differentiated Thyroid Cancer1
4CompletedNot AvailableThyroid Cancers1
4CompletedTreatmentHypothyroidism / Neoplasms, Thyroid1
Not AvailableActive Not RecruitingTreatmentThyroid Carcinoma1

Pharmacoeconomics

Manufacturers
  • Sanofi aventis us llc
  • Genzyme corp
Packagers
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntramuscular.9 mg/mL
Kit
Powder, for solutionIntramuscular0.9 mg
Prices
Unit descriptionCostUnit
Thyrogen 1.1 mg vial1196.4USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5840566No1995-11-242015-11-24Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)55 °CNot Available
hydrophobicity-0.330Not Available
isoelectric point7.50Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Thyroid-stimulating hormone receptor activity
Specific Function
Receptor for thyrothropin. Plays a central role in controlling thyroid cell metabolism. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Also acts as a rece...
Gene Name
TSHR
Uniprot ID
P16473
Uniprot Name
Thyrotropin receptor
Molecular Weight
86828.965 Da
References
  1. Szkudlinski MW: Recombinant human thyrotropins of the twenty-first century. Expert Opin Pharmacother. 2004 Dec;5(12):2435-40. [PubMed:15571461]
  2. Conway GS: Clinical manifestations of genetic defects affecting gonadotrophins and their receptors. Clin Endocrinol (Oxf). 1996 Dec;45(6):657-63. [PubMed:9039330]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on October 23, 2017 14:13