Find Lusutrombopag manufacturers, exporters & distributors on PharmaCompass

Lusutrombopag

Granules India Limited has high volume world-class facilities for APIs, PFIs, & FDFs, serving customers in over 80 countries.

ACCESS ALL DATA
Browse all information
CHEMISTRY
Discover Molecule Insights

ACTIVE PHARMA INGREDIENTS

1 API Suppliers, 1 NDC API, 1 Listed Suppliers

1 API Suppliers
1 NDC API
1 Listed Suppliers

FINISHED DOSAGE FORMULATIONS

1 FDF Dossiers, 1 FDA Orange Book

1 FDF Dossiers
1 FDA Orange Book

DIGITAL CONTENT

1 DATA COMPILATION #PharmaFlow, 7 NEWS #PharmaBuzz

media
1 DATA COMPILATION #PharmaFlow
7 NEWS #PharmaBuzz

GLOBAL SALES INFORMATION

1 US Medicaid Prescriptions, 6 Annual Reports

globalSalesInformation
1 US Medicaid Prescriptions
6 Annual Reports

MARKET PLACE

1 APIs

marketPlace
1 APIs

PATENTS & EXCLUSIVITIES

4 US Patents

patents
4 US Patents

Synopsis

ACTIVE PHARMA INGREDIENTS

API Suppliers

USDMF

CEP/COS

JDMF

EU WC

KDMF

NDC API

VMF

Listed Suppliers

API REF. PRICE (USD/KG)

$ 0

MARKET PLACE

API

FDF

0INTERMEDIATES

FINISHED DOSAGE FORMULATIONS

FDF Dossiers

FDA Orange Book

Europe

Canada

Australia

South Africa

Listed Dossiers

0 DRUGS IN DEVELOPMENT

DRUG PRODUCT COMPOSITIONS

REF. STANDARDS OR IMPURITIES

EDQM

USP

Others

PATENTS & EXCLUSIVITIES

US Patents

US Exclusivities

Health Canada Patents

DIGITAL CONTENT

Data Compilation #PharmaFlow

Stock Recap #PipelineProspector

Weekly News Recap #Phispers

News #PharmaBuzz

GLOBAL SALES INFORMATION

US Medicaid (USD)

324,612

Annual Reports (USD Million)

Finished Drug Prices

0RELATED EXCIPIENT COMPANIES

0EXCIPIENTS BY APPLICATIONS

Chemistry

Click the arrow to open the dropdown

Click the button for full data set

Also known as: 1110766-97-6, Mulpleta, S-888711, 6ll5jfu42f, Rsc888711, (e)-3-[2,6-dichloro-4-[[4-[3-[(1s)-1-hexoxyethyl]-2-methoxyphenyl]-1,3-thiazol-2-yl]carbamoyl]phenyl]-2-methylprop-2-enoic acid

Molecular Formula

C₂₉H₃₂Cl₂N₂O₅S

Molecular Weight

591.5 g/mol

InChI Key

NOZIJMHMKORZBA-KJCUYJGMSA-N

FDA UNII

6LL5JFU42F

Lusutrombopag is an orally bioavailable thrombopoietin receptor (TPOR) agonist developed by Shionogi & Company (Osaka, Japan). TPOR is a regulatory target site for endogenous thrombopoietin, which acts as a primary cytokine to promote megakaryocyte proliferation and differentiation, and affect other hematopoietic lineages as well, including erythroid, granulocytic and lymphoid lineages. Thrombocytopenia, which indicates abnormally low levels of platelets, is a common complication related to chronic liver disease. This hematological abnormality, especially in cases of severe thrombocytopenia (platelet count <50,000/L), creates challenges to patients requiring invasive medical procedures where there is a significant risk for spontaneous bleeding. Lusutrombopag binds to the transmembrane domain of TPOR expressed on megakaryocytes, and causes the proliferation and differentiation of megakaryocytic progenitor cells from hematopoietic stem cells. In September 2015, lusutrombopag received its first global approval in Japan to reduce the need for platelet transfusion in adults with chronic liver disease and thrombocytopenia who are schedule to undergo an invasive medical procedure. Lusutrombopag was approved by the FDA on July 31st, 2018 for the same therapeutic indication under the market name Mulpleta. In two randomized, double-blind, placebo-controlled trials, patients with chronic liver disease and severe thrombocytopenia who were undergoing an invasive procedure with a platelet count less than 50 x 10^9/L were administered lusutrombopag orally. Higher percentages (65-78%) of the patients receiving lusutrombopag required no platelet transfusion prior to the primary invasive procedure compared to those receiving placebo. Lusutrombopag is currently in phase III development in various European countries including Austria, Belgium, Germany, and the UK.

1 2D Structure

Lusutrombopag

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

(E)-3-[2,6-dichloro-4-[[4-[3-[(1S)-1-hexoxyethyl]-2-methoxyphenyl]-1,3-thiazol-2-yl]carbamoyl]phenyl]-2-methylprop-2-enoic acid

2.1.2 InChI

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

2.1.3 InChI Key

NOZIJMHMKORZBA-KJCUYJGMSA-N

2.1.4 Canonical SMILES

CCCCCCOC(C)C1=CC=CC(=C1OC)C2=CSC(=N2)NC(=O)C3=CC(=C(C(=C3)Cl)C=C(C)C(=O)O)Cl

2.1.5 Isomeric SMILES

CCCCCCO[C@@H](C)C1=CC=CC(=C1OC)C2=CSC(=N2)NC(=O)C3=CC(=C(C(=C3)Cl)/C=C(\C)/C(=O)O)Cl

2.2 Other Identifiers

2.2.1 UNII

6LL5JFU42F

2.3 Synonyms

2.3.1 MeSH Synonyms

1. Mulpleta

2.3.2 Depositor-Supplied Synonyms

1. 1110766-97-6

2. Mulpleta

3. S-888711

4. 6ll5jfu42f

5. Rsc888711

6. (e)-3-[2,6-dichloro-4-[[4-[3-[(1s)-1-hexoxyethyl]-2-methoxyphenyl]-1,3-thiazol-2-yl]carbamoyl]phenyl]-2-methylprop-2-enoic Acid

7. (s,e)-3-(2,6-dichloro-4-((4-(3-(1-(hexyloxy)ethyl)-2-methoxyphenyl)thiazol-2-yl)carbamoyl)phenyl)-2-methylacrylic Acid

8. (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

9. Lusutrombopag [inn]

10. Unii-6ll5jfu42f

11. Lusutrombopag [usan:inn]

12. Mulpleta (tn)

13. 2-propenoic Acid, 3-(2,6-dichloro-4-(((4-(3-((1s)-1-(hexyloxy)ethyl)-2-methoxyphenyl)-2-thiazolyl)amino)carbonyl)phenyl)-2-methyl-, (2e)-

14. S 888711

15. Lusutrombopags-888711

16. Lusutrombopag [mi]

17. Lusutrombopag [jan]

18. Lusutrombopag [usan]

19. Lusutrombopag [who-dd]

20. Schembl3062080

21. Schembl3062084

22. Chembl2107831

23. Lusutrombopag (jan/usan/inn)

24. Gtpl10032

25. Chebi:136051

26. Dtxsid701027951

27. Lusutrombopag [orange Book]

28. 2-propenoic Acid, 3-[2,6-dichloro-4-[[[4-[3-[(1s)-1-(hexyloxy)ethyl]-2-methoxyphenyl]-2-thiazolyl]amino]carbonyl]phenyl]-2-methyl-, (2e)-

29. Ex-a1290

30. Mfcd28502075

31. S6988

32. Zinc84759273

33. Cs-6137

34. Db13125

35. Ncgc00522464-01

36. (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

37. Ac-30601

38. As-52368

39. Hy-19883

40. J3.505.027b

41. D10476

42. A927042

43. S888711

44. Q27265116

45. (e)-3-[2,6-dichloro-4-[4-[3-[(s)-1-hexyloxyethyl]-2-methoxyphenyl]thiazol-2-ylcarbamoyl]phenyl]-2-methylacrylic Acid

2.4 Create Date

2011-01-31

3 Chemical and Physical Properties

Molecular Formula	C₂₉H₃₂Cl₂N₂O₅S
Molecular Weight	591.5 g/mol
XLogP3	7.7
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	13
Exact Mass	590.1408987 g/mol
Monoisotopic Mass	590.1408987 g/mol
Topological Polar Surface Area	126 Å²
Heavy Atom Count	39
Formal Charge	0
Complexity	822
Isotope Atom Count	0
Defined Atom Stereocenter Count	1
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	1
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug Indication

Lusutrombopag is indicated for the treatment of thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure.

FDA Label

Mulpleo is indicated for the treatment of severe thrombocytopenia in adult patients with chronic liver disease undergoing invasive procedures

Treatment of thrombocytopenia secondary to liver disease

5 Pharmacology and Biochemistry

5.1 Pharmacology

The AUC of lusutrombopag was found to correlate the increased platelet counts. Following administration of 3 mg daily dose in patients with chronic liver disease and thrombocytopenia, the mean (standard deviation) maximum platelet count in patients (N=74) without platelet transfusion was 86.9 (27.2) 10^9/L, and the median time to reach the maximum platelet count was 12.0 (5 to 35) days. Lusutrombopag was not shown to induce any clinically significant QTc prolongation at a dose 8 times the recommended dosage.

5.2 ATC Code

B02BX

B - Blood and blood forming organs

B02 - Antihemorrhagics

B02B - Vitamin k and other hemostatics

B02BX - Other systemic hemostatics

B02BX07 - Lusutrombopag

5.3 Absorption, Distribution and Excretion

Absorption

Lusutrombopag is rapidly absorbed following oral administration. It exhibited a doseproportional pharmacokinetic profile over the single dose range of 1 mg to 50 mg, which was similar in both healthy subjects and those with chronic liver disease. A geometric mean (%CV) maximal concentration (Cmax) and area under the curve (AUC) in healthy subjects receiving 3 mg of lusutrombopag were 111 (20.4) ng/mL and 2931 (23.4) ng.hr/mL. The accumulation ratios of Cmax and AUC were approximately 2 with oncedaily multipledose administration, and steadystate plasma lusutrombopag concentrations were achieved after Day 5. The time to reach peak plasma concentrations (Tmax) were approximately 6 to 8 hours after oral administration in patients with chronic liver disease. Food consumption is not reported to affect the absorption and bioavailability of lusutrombopag.

Route of Elimination

About 1% of the administered dose of lusutrombopag undergoes urinary excretion. Fecal excretion accounted for 83% of the total dose, where 16% of the dose was excreted as unchanged parent compound.

Volume of Distribution

The mean (%CV) lusutrombopag apparent volume of distribution in healthy adult subjects was 39.5 (23.5) L.

Clearance

The approximate mean (%CV) clearance of lusutrombopag in patients with chronic liver disease is estimated to be 1.1 (36.1) L/hr.

5.4 Metabolism/Metabolites

CYP4 enzymes predominantly contribute to the metabolism of lusutrombopag, especially CYP4A11. Lusutrombopag is reported to mainly undergo - and -oxidation, as well as glucuronidation.

5.5 Biological Half-Life

In healthy adult subjects, the terminal elimination halflife (t1/2) was approximately 27 hours.

5.6 Mechanism of Action

Lusutrombopag mimics the biological actions of endogenous thrombopoietin (TPO) by acting as an agonist for the thrombopoietin receptor (TPOR) expressed on megakaryocytes. It binds to the transmembrane domain of the receptor and induces thrombocytopoiesis by targeting the same signal transduction system as that of endogenous TPO, which involves the activation of JAK and STAT pathways. It stimulates the proliferation and differentiation of bone marrow progenitor cells into megakaryocytes, which undergoes maturation to act as precursor cells for platelets. A single megakaryocyte produces and releases thousands of platelets upon maturation and series of remodeling events. Lusutrombopag displays high specificity towards human TPORs when compared to murine TPORs. Lusutrombopag may affect other hematopoietic lineages as well, including erythroid, granulocytic and lymphoid lineages. One case of increased leukocyte and erythrocyte counts that prolonged for over 120 days was reported following administration in a patient with liver cirrhosis (LC) due to hepatitis C virus.

API SUPPLIERS