LUSUTROMBOPAG

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H32Cl2N2O5S
Molecular Weight	591.546
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCCO[C@@H](C)C1=C(OC)C(=CC=C1)C2=CSC(NC(=O)C3=CC(Cl)=C(\C=C(/C)C(O)=O)C(Cl)=C3)=N2

InChI

InChIKey=NOZIJMHMKORZBA-KJCUYJGMSA-N

InChI=1S/C29H32Cl2N2O5S/c1-5-6-7-8-12-38-18(3)20-10-9-11-21(26(20)37-4)25-16-39-29(32-25)33-27(34)19-14-23(30)22(24(31)15-19)13-17(2)28(35)36/h9-11,13-16,18H,5-8,12H2,1-4H3,(H,35,36)(H,32,33,34)/b17-13+/t18-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26666417
Curator's Comment: description was created based on several sources, including http://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/340018_3399010F1022_1_02#page=4 | https://www.ncbi.nlm.nih.gov/pubmed/28324272 | https://www.ncbi.nlm.nih.gov/pubmed/27209291

Lusutrombopag (trade name Mulpleta) is an orally bioavailable, small molecule thrombopoietin (TPO) receptor agonist being developed by Shionogi for chronic liver disease (CLD) patients with thrombocytopenia prior to elective invasive surgery. Lusutrombopag acts selectively on the human TPO receptor and activates signal transduction pathways that promote the proliferation and differentiation of bone marrow cells into megakaryocytes, thereby increasing platelet levels. In September 2015, Lusutrombopag received its first global approval in Japan for the improvement of CLD-associated thrombocytopenia in patients scheduled to undergo elective invasive procedures. Oral Lusutrombopag is rapidly absorbed, with a median time to maximum serum concentration (Tmax) of 3.8–4.0 h in healthy subjects administered single doses of oral Lusutrombopag 1, 2 or 4 mg, and 6 h in CLD patients with thrombocytopenia administered oral Lusutrombopag 3 mg once daily for 7 days. The major metabolic pathway for Lusutrombopag appears to be omega- and beta-oxidation. Lusutrombopag is a substrate of breast cancer resistance protein and P-glycoprotein, according to in vitro data.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thrombopoietin receptor 8 Target ID: CHEMBL1864 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26666417	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic liver disease 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02389621	Primary		Approved 8429	Mulpleta Approved Use Unknown Launch Date 1.44227526E12

C_max

Value	Dose	Analyte	Population
181 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lusutrombopag-shionogi-epar-public-assessment-report_en.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LUSUTROMBOPAG plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
170 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lusutrombopag-shionogi-epar-public-assessment-report_en.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LUSUTROMBOPAG plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
191 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lusutrombopag-shionogi-epar-public-assessment-report_en.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LUSUTROMBOPAG plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
217 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lusutrombopag-shionogi-epar-public-assessment-report_en.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LUSUTROMBOPAG plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
3381 ng × h/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lusutrombopag-shionogi-epar-public-assessment-report_en.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LUSUTROMBOPAG plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3678 ng × h/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lusutrombopag-shionogi-epar-public-assessment-report_en.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LUSUTROMBOPAG plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
4187 ng × h/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lusutrombopag-shionogi-epar-public-assessment-report_en.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LUSUTROMBOPAG plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4808 ng × h/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/lusutrombopag-shionogi-epar-public-assessment-report_en.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LUSUTROMBOPAG plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 mg 1 times / day steady, oral Recommended Dose: 3 mg, 1 times / day Route: oral Route: steady Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210923s000lbl.pdf	unhealthy n = 171 Health Status: unhealthy Condition: thrombocytopeni Population Size: 171 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210923s000lbl.pdf	Other AEs: Headache, Portal vein thrombosis... Other AEs: Headache (5%) Portal vein thrombosis (serious, 5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210923s000lbl.pdf
3 mg 1 times / day steady, oral Recommended Dose: 3 mg, 1 times / day Route: oral Route: steady Dose: 3 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf	unhealthy n = 171 Health Status: unhealthy Condition: thrombocytopeni Population Size: 171 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf	Other AEs: Vomiting, Anemia... Other AEs: Vomiting (1.17%) Anemia (2.34%) Splenomegaly (1.17%) Atrial fibrillation (1.17%) Cardiac arrest (0.58%) Cardiac ventricular thrombosis (0.58%) Ascites (5.85%) Abdominal distension (1.17%) Constipation (6.43%) Diarrhea (4.09%) Hemorrhagic erosive gastritis (0.58%) Mesenteric vein thrombosis (0.58%) Nausea (1.75%) Rectal hemorrhage (0.58%) Upper gastrointestinal hemorrhage (0.58%) Acute hepatic failure (0.58%) Hepatic function abnormal (1.17%) Portal hypertension (0.58%) Nasopharyngitis (5.26%) Bronchitis (0.58%) Aspartate aminotransferase increased (24%) Alanine aminotransferase increased (16.4%) Fibrin D dimer increased (7.01%) Fibrin degradation products increased (5.85%) Blood bilirubin increased (7.6%) Oxygen saturation decreased (10.5%) Fatigue (3.51%) Peripheral edema (0.58%) Pyrexia (4.68%) Cough (1.17%) Pruritis (2.92%) Rash (2.34%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 substrate 1737	inducer 389 substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 OATP1B1 788 OATP1B3 706 OCT1 512 OAT1 599 OAT3 642 OCT2 647 BSEP 402 CYP 111	P-gp 1537 BCRP 561 CYP1A2 1054 CYP2C19 991 CYP4A11 119	CYP1A2 701 UGT1A6 34 UGT2B7 14

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=54 Page: 54.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
UGT1A6 141	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no
UGT2B7 157	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=71 Page: 71.0	no

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.1080/00498254.2020.1845416?needAccess=true Page: -	inconclusive
CYP4A11 119	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.1080/00498254.2020.1845416?needAccess=true Page: -	inconclusive
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=54 Page: 54.0	yes
CYP2C19 991	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.1080/00498254.2020.1845416?needAccess=true Page: -	yes
CYP2C9 1037	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.1080/00498254.2020.1845416?needAccess=true Page: -	yes
CYP2D6 1217	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.1080/00498254.2020.1845416?needAccess=true Page: -	yes
CYP3A4 1737	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.1080/00498254.2020.1845416?needAccess=true Page: -	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210923Orig1s000MultidisciplineR.pdf#page=54 Page: 54.0	yes

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA008ZS5	https://www.aablocks.com/goods/Goods/detail?id=AA008ZS5
Aaron Chemicals	AR0090JX	http://www.aaronchem.com/1110766-97-6
AbMole Bioscience	M9458	http://www.abmole.com/products/lusutrombopag.html
Chem Scene	CS-6137	http://www.chemscene.com/1110766-97-6.html
Chemspace	CSSB00025715565	https://chem-space.com/CSSB00025715565
DC Chemicals	DC9938	http://www.dcchemicals.com/product_show-Lusutrombopag_S_888711_.html
Excenen	EX-A1290	http://www.excenen.com/searchresultlist.php?id=1110766-97-6
MedChem Express	HY-19883	https://www.medchemexpress.com/Lusutrombopag.html
Selleck Chemicals	S6988	http://www.selleckchem.com/products/lusutrombopag.html
Smolecule	S533858	http://www.smolecule.com/products/s533858
Synblock Inc	SB16975	http://www.synblock.com/product/1110766-97-6.html
THE BioTek	bt-274793	https://www.thebiotek.com/product/inhibitors/bt-274793
abcr GmbH	AB485657	http://www.abcr.com/shop/en/AB485657
eNovation Chemicals	D572889	https://www.enovationchem.com/ProductDetails.asp?ProductID=D572889
eNovation Chemicals	D575046	https://www.enovationchem.com/ProductDetails.asp?ProductID=D575046
eNovation Chemicals	Y0975666	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0975666
eNovation Chemicals	Y1012603	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y1012603
iChemical	EBD4033743	http://www.ichemical.com/products/1110766-97-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Lusutrombopag: First Global Approval.	2016 Jan	26666417
Population Pharmacokinetic and Pharmacodynamic Modeling of Lusutrombopag, a Newly Developed Oral Thrombopoietin Receptor Agonist, in Healthy Subjects.	2016 Nov	27209291

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of oral lusutrombopag is 3 mg once daily for 7 days. It should be avoided in patients undergoing open-heart surgery, brain surgery with craniotomy organ resection or a laparotomy.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

LUSUTROMBOPAG

Official Name

English

LUSUTROMBOPAG [USAN]

Common Name

English

(2E)-3-{2,6-Dichloro-4-[(4-{3-[(1S)-1-(hexyloxy)ethyl]-2-methoxyphenyl}-1,3-thiazol-2-yl)carbamoyl]phenyl}-2-methylprop-2-enoic acid

Systematic Name

English

LUSUTROMBOPAG [ORANGE BOOK]

Common Name

English

2-PROPENOIC ACID, 3-(2,6-DICHLORO-4-(((4-(3-((1S)-1-(HEXYLOXY)ETHYL)-2-METHOXYPHENYL)-2-THIAZOLYL)AMINO)CARBONYL)PHENYL)-2-METHYL-, (2E)-

Common Name

English

lusutrombopag [INN]

Common Name

English

MULPLETA

Brand Name

English

RSC888711

Code

English

S-888711

Code

English

LUSUTROMBOPAG [JAN]

Common Name

English

Lusutrombopag [WHO-DD]

Common Name

English

LUSUTROMBOPAG [MI]

Common Name

English

Classification Tree Code System Code

WHO-ATC

B02BX07