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Details

Stereochemistry ACHIRAL
Molecular Formula C25H22N4O4
Molecular Weight 442.4666
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of ELTROMBOPAG

SMILES

CC1=NN(C(=O)\C1=N/NC2=C(O)C(=CC=C2)C3=CC(=CC=C3)C(O)=O)C4=CC(C)=C(C)C=C4

InChI

InChIKey=XDXWLKQMMKQXPV-QYQHSDTDSA-N
InChI=1S/C25H22N4O4/c1-14-10-11-19(12-15(14)2)29-24(31)22(16(3)28-29)27-26-21-9-5-8-20(23(21)30)17-6-4-7-18(13-17)25(32)33/h4-13,26,30H,1-3H3,(H,32,33)/b27-22-

HIDE SMILES / InChI

Molecular Formula C25H22N4O4
Molecular Weight 442.4666
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

Eltrombopag is a thrombopoietin (TPO) nonpeptide mimetic administered orally that activates the TPO receptor by binding to the transmembrane domain and initiates signaling cascades that induce proliferation and differentiation of megakaryocytes from bone marrow progenitor cells. Eltrombopag under brand name promacta is approved for the treatment of the low blood platelet counts in adults with chronic immune (idiopathic) thrombocytopenia (ITP), when certain other medicines, or surgery to remove the spleen, have not worked well enough. ITP is a condition that may cause unusual bruising or bleeding due to an abnormally low number of platelets in the blood. Eltrombopag has also been approved for the treatment of thrombocytopenia (low blood platelet counts) in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy and to treat patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

CNS Activity

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions
PubMed

PubMed

TitleDatePubMed
UDP-glucuronosyltransferases and clinical drug-drug interactions.
2005 Apr
Eltrombopag: Is this "24 karat gold platelet" treatment for thrombocytopenia in cirrhosis associated with hepatitis C?
2008 Apr
Eltrombopag: an effective remedy for thrombocytopaenia?
2008 Jun
Metabolism and disposition of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, in healthy human subjects.
2011 Sep
The biology of thrombopoietin and thrombopoietin receptor agonists.
2013 Jul
Patents

Sample Use Guides

In Vivo Use Guide
Chronic Immune (Idiopathic) Thrombocytopenia: use the lowest dose of PROMACTA (eltrombopag) to achieve and maintain a platelet count greater than or equal to 50 x 109 /L as necessary to reduce the risk for bleeding. Dose adjustments are based upon the platelet count response. Initial Dose Regimen: Adult and Pediatric Patients 6 Years and Older with ITP: Initiate PROMACTA at a dose of 50 mg once daily, except in patients who are of East Asian ancestry (such as Chinese, Japanese, Taiwanese, or Korean) or who have mild to severe hepatic impairment (Child-Pugh Class A, B, C). For patients of East Asian ancestry with ITP, initiate PROMACTA at a reduced dose of 25 mg once daily. For patients with ITP and mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C), initiate PROMACTA at a reduced d ose of 25 mg once daily. For patients of East Asian ancestry with ITP and hepatic impairment (Child-Pugh Class A, B, C), consider initiating PROMACTA at a reduced dose of 12.5 mg once daily. Pediatric Patients with ITP Aged 1 to 5 Years: Initiate PROMACTA at a dose of 25 mg once daily. Monitoring and Dose Adjustment: After initiating PROMACTA, adjust the dose to achieve and maintain a platelet count greater than or equal to 50 x 109 /L as necessary to reduce the risk for bleeding. Do not exceed a dose of 75 mg daily. Monitor clinical hematology and liver tests regularly throughout therapy with PROMACTA and modify the dosage regimen of PROMACTA based on platelet counts as outlined in Table 1. During therapy with PROMACTA, assess CBCs with differentials, including platelet counts, weekly until a stable platelet count has been achieved. Obtain CBCs with differentials, including platelet counts, monthly thereafter. When switching between Chronic Hepatitis C-associated Thrombocytopenia Use the lowest dose of PROMACTA to achieve and maintain a platelet count necessary to initiate and maintain antiviral therapy with pegylated interferon and ribavirin. Dose adjustments are based upon the platelet count response. Do not use PROMACTA to normalize platelet counts. In clinical trials, platelet counts generally began to rise within the first week of treatment with PROMACTA. Initial Dose Regimen: Initiate PROMACTA at a dose of 25 mg once daily. Monitoring and Dose Adjustment: Adjust the dose of PROMACTA in 25-mg increments every 2 weeks as necessary to achieve the target platelet count required to initiate antiviral therapy. Monitor platelet counts every week prior to starting antiviral therapy. During antiviral therapy, adjust the dose of PROMACTA to avoid dose reductions of peginterferon. Monitor CBCs with differentials, including platelet counts, weekly during antiviral therapy until a stable platelet count is achieved. Monitor platelet counts monthly thereafter. Do not exceed a dose of 100 mg daily. Monitor clinical hematology and liver tests regularly throughout therapy with PROMACTA.
Route of Administration: Oral
In Vitro Use Guide
It was investigated eltrombopag's effects on human UCB hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) expansion, and its effects on hematopoiesis in vivo. Eltrombopag selectively augmented the expansion of human CD45+, CD34+, and CD41+ cells in bone marrow compartment without effects on mouse bone marrow cells in the NOD/SCID mice xenotrans plant model. Eltrombopag increased peripheral human platelets and white blood cells. Both eltrombopag and recombinant human TPO (rhTPO) induced phosphorylation of STAT5 of CD34+ CD41-, CD34- CD41+, and CD34- CD41- cells. For this purpose the cells were treated with 100ng/ml rhTPO or 3μg/ml eltrombopag for 10 to 60 minutes at 37°C. rhTPO preferentially induced pSTAT3, pAKT, and more pSTAT5 in CD34- C41+ cells, while eltrombopag had no effects on pSTAT3. Eltrombopag differed somewhat from rhTPO in the signal transduction pathways by favoring earlier HSC/HPC populations.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:30:14 UTC 2019
Edited
by admin
on Mon Oct 21 20:30:14 UTC 2019
Record UNII
S56D65XJ9G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ELTROMBOPAG
DASH   EMA EPAR   INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
SB497115
Code English
ELTROMBOPAG [INN]
Common Name English
ELTROMBOPAG [EMA EPAR]
Common Name English
(1,1'-BIPHENYL)-3-CARBOXYLIC ACID, 3'-((2Z)-(1-(3,4-DIMETHYLPHENYL)-1,5-DIHYDRO-3-METHYL-5-OXO-4H-PYRAZOL-4-YLIDENE)HYDRAZINO)-2'-HYDROXY-
Common Name English
3'-((2Z)-2-(1-(3,4-DIMETHYLPHENYL)-3-METHYL-5-OXO-1,5-DIHYDRO-4H-PYRAZOL-4-YLIDENE)DIAZANYL)-2'-HYDROXYBIPHENYL-3-CARBOXYLIC ACID
Systematic Name English
(1,1'-BIPHENYL)-3-CARBOXYLIC ACID, 3'-(2-(1-(3,4-DIMETHYLPHENYL)-4,5-DIHYDRO-3-METHYL-5-OXO-1H-PYRAZOL-4-YL)DIAZENYL)-2'-HYDROXY-
Systematic Name English
ELTROMBOPAG [MART.]
Common Name English
ELTROMBOPAG [MI]
Common Name English
ELTROMBOPAG [WHO-DD]
Common Name English
ELTROMBOPAG [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175969
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
NCI_THESAURUS C78275
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
NDF-RT N0000175968
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
LIVERTOX 344
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
FDA ORPHAN DRUG 251907
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
WHO-VATC QB02BX05
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
FDA ORPHAN DRUG 410213
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
NDF-RT N0000175973
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
NDF-RT N0000175970
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
WHO-ATC B02BX05
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
NDF-RT N0000178368
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
NDF-RT N0000175967
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL461101
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
INN
8655
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
NCI_THESAURUS
C71634
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
MESH
C520809
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
IUPHAR
6961
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
RXCUI
711942
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY RxNorm
MERCK INDEX
M4879
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY Merck Index
NDF-RT
N0000191277
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY UGT1A6 Inhibitors [MoA]
CAS
496775-61-2
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
NDF-RT
N0000191274
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY UGT2B15 Inhibitors [MoA]
CAS
376591-99-0
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
NON-SPECIFIC STEREOCHEMISTRY
NDF-RT
N0000191272
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY UGT1A1 Inhibitors [MoA]
EPA CompTox
496775-61-2
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
EVMPD
SUB30140
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
HSDB
496775-61-2
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
DRUG BANK
DB06210
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
CAS
2097678-09-4
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
ALTERNATIVE
NDF-RT
N0000191278
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY UGT1A9 Inhibitors [MoA]
WIKIPEDIA
ELTROMBOPAG
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY
NDF-RT
N0000191276
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY UGT1A4 Inhibitors [MoA]
NDF-RT
N0000191275
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY UGT1A3 Inhibitors [MoA]
NDF-RT
N0000190113
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
NDF-RT
N0000190107
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
NDF-RT
N0000191273
Created by admin on Mon Oct 21 20:30:14 UTC 2019 , Edited by admin on Mon Oct 21 20:30:14 UTC 2019
PRIMARY UGT2B7 Inhibitors [MoA]
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC in healthy subjects