Delving into the Latest Updates on Lusutrombopag with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Lusutrombopag (JAN/USAN/INN)

+ [4]

Target

TPO receptor

Mechanism

TPO receptor agonists(Thrombopoietin receptor agonists)

Therapeutic Areas

Hemic and Lymphatic Diseases

Active Indication

Thrombocytopenia

Inactive Indication

Chronic liver diseaseChronic thrombocytopeniaPurpura, Thrombocytopenic, Idiopathic

Originator Organization

Shionogi & Co., Ltd.

Active Organization

Shionogi, Inc.Qualicaps Netherlands BV

Suzhou SIKRO Pharmaceutical Co., Ltd

+ [2]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (28 Sep 2015),

Thrombocytopenia

RegulationFast Track (US), Priority Review (US)

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Structure

Molecular FormulaC29H32Cl2N2O5S

InChIKeyNOZIJMHMKORZBA-KJCUYJGMSA-N

CAS Registry1110766-97-6

Thrombocytopenia is one of the common complications with the hematologic system in patients with chronic liver disease, which often causes poor quality of life and high risk of bleeding, thereby affecting their diagnosis, treatment, and prognosis. Platelet transfusion can improve the patient's declining platelet count to a certain extent, but it has problems such as high price and being easy to cause immune rejection. Thrombopoietin (TPO), as an important cytokine that affects platelet production, can bind to TPO receptors and activate megakaryocytes to produce platelets. Lusutrombopag is a newly developed small-molecule TPO receptor agonist that can induce bone marrow progenitor cells to differentiate into megakaryocytes and increase platelet production, posing characteristics of oral convenience, safety and effectiveness; thus, it has been used in many countries and regions for the treatment of patients with chronic liver diseases concurrent with thrombocytopenia. Herein, the pharmacological features and clinical research are reviewed.

06 Sep 2024·The Journal of Organic Chemistry

Asymmetric Transfer Hydrogenation of Ketones Improved by PNN–Manganese Complexes

Article

Author: Yan, Xiuli ; Wang, Zheng ; Ma, Zhifeng ; Solan, Gregory A. ; Wang, Jingyao ; Liu, Qingbin ; Su, Yi ; Ma, Ning ; Li, Libin

Chiral manganese(I) complexes that contain carbocyclic-fused 8-amino-5,6,7,8-tetrahydroquinolinyl groups that are appended with distinct para-R substituents have proven to be effective catalysts in the asymmetric transfer hydrogenation (ATH) of a wide range of ketones (48 examples). Notably, Mn2 proved to be the most productive catalyst, allowing an outstanding turnover number of 8300 with catalyst loadings as low as 0.01 mol %. Furthermore, this catalytic protocol shows considerable promise for applications in the synthesis of chiral drugs such as Lusutrombopag.

01 Aug 2024·Hämostaseologie

Update on the Use of Thrombopoietin-Receptor Agonists in Pediatrics

Review

Author: Streif, Werner ; Dame, Christof ; Gebetsberger, Jennifer

AbstractThis review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for pediatric patients. Romiplostim and eltrombopag are already established as second-line treatment for persistent or chronic immune thrombocytopenia (ITP). As in adults, TPO-RAs are currently also evaluated in severe aplastic anemia (SAA), chemotherapy-induced thrombocytopenia (CIT), myelodysplastic syndromes (MDS), and poor engraftment after hematopoietic stem cell transplantation in pediatric and adolescent patients. Moreover, studies on the implication of TPO-RA in treating rare inherited thrombocytopenias, such as Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia (CAMT), or MYH9-associated thrombocytopenia, deserve future attention. Current developments include testing of avatrombopag and lusutrombopag that are approved for the treatment of thrombocytopenia associated with chronic liver disease (CLD) in adult patients. In pediatric and adolescent medicine, we expect in the near future a broader use of TPO-RAs as first-line treatment in primary ITP, thereby considering immunomodulatory effects that increase the rate of sustained remission off-treatment, and a selective use in rare inherited thrombocytopenias based on current clinical trials.

100 Deals associated with Lusutrombopag

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External Link

KEGG	Wiki	ATC	Drug Bank
D10476	Lusutrombopag	B02BX07	DB13125

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Thrombocytopenia	JP	Shionogi & Co., Ltd.	28 Sep 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic thrombocytopenia	Preclinical	US	Shionogi, Inc.	29 Apr 2010
Purpura, Thrombocytopenic, Idiopathic	Preclinical	US	Shionogi, Inc.	18 Mar 2010
Chronic liver disease	Discovery	-	Shionogi, Inc.	15 Jun 2015
Thrombocytopenia	Discovery	-	Shionogi, Inc.	15 Jun 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CTR20192384 (Pubmed) Manual	Phase 3	Thrombocytopenia \| Chronic liver disease	66	Lusutrombopag	thskwipcgo(pgwadcngoj) = icnedwxndx idnmcypfce (gegbrgzeuy ) View more	Positive	18 Oct 2022
				Placebo	thskwipcgo(pgwadcngoj) = qzvmoacquc idnmcypfce (gegbrgzeuy ) View more
NCT02389621 (L-PLUS 2, Pubmed)	Phase 3	Thrombocytopenia \| Chronic liver disease	215	Lusutrombopag 3mg	tsmfnzxczv(motcahyxme) = One patient from the phase 1/2 study had a non-serious portal vein thrombosis, which was not considered treatment-related gfjudscyst (nzbujcxxxn ) View more	-	29 Jul 2022
NCT01129024 (CTgov)	Phase 2	Purpura, Thrombocytopenic, Idiopathic \| Chronic thrombocytopenia	19	Lusutrombopag	rxtzzklkng(nqkqxinnhy) = vvozjfcrxu qzxwfgvmtf (otcuywbsps, xjebkiqtcn - nuvxutsjoq) View more	-	26 Feb 2021
NCT01054443 (CTgov)	Phase 2	Purpura, Thrombocytopenic, Idiopathic	20	Placebo (Placebo)	efeyqjixra(glfrltqxqy) = erxiyyorxp snfchegsxy (vhnpmmlnxh, dajkwoqved - msozkvenak) View more	-	24 Feb 2021
				Lusutrombopag (Lusutrombopag 0.5 mg)	efeyqjixra(glfrltqxqy) = iovhmackaq snfchegsxy (vhnpmmlnxh, jfaoqwfnby - oodkdtwyor) View more
ISTH2019	Phase 1	Chronic liver disease	8	Lusutrombopag 3 mg	(sfnaboyzhc) = pinzuxuxlv jpbriwaizl (xxyrjragov )	-	10 Jun 2019
EASL2019	Not Applicable	Thrombocytopenia \| Chronic liver disease	-	Lusutrombopag 3 mg	puemiikzrg(zwxolhoizi) = Lower BE rates, regardless of severity and timing of onset, were observed for LUSU alone vs PBO+PT. Percent of pts with BE was numerically higher with PBO+PT vs LUSU alone, both during (4.8% vs 3.2%) and post-procedure (7.1% vs 4.0%). Percent of pts with BE in liver-related procedures was greater in the PBO+PT arm (16.1%) vs LUSU alone (11.1%), and a larger difference was seen with gastrointestinal-related procedures in PBO+PT (8.9%) vs LUSU alone (2.0%) tmsruremjb (eofccuomql )	-	13 Apr 2019
				Placebo+Platelet Transfusion
L-PLUS 1 and L-PLUS 2 (UEGW2018)	Phase 3	Chronic liver disease	427	Lusutrombopag 3 mg	(valbriwueb) = efkcyjagvh qmbazdbhbp (pyynxogxjb ) View more	Positive	01 Oct 2018
				Placebo	(valbriwueb) = vgtwgjuxxa qmbazdbhbp (pyynxogxjb ) View more
NCT02389621 (L-PLUS 2, CTgov)	Phase 3	Thrombocytopenia \| Chronic liver disease	215	Lusutrombopag (Lusutrombopag)	ooovoowvqh(cgdlikvnsf) = svdaohblkf xiimyzbbnp (pcfovwklru, dmyleqawdn - hhpzswcssw) View more	-	25 Sep 2018
				Placebo (Placebo)	ooovoowvqh(cgdlikvnsf) = bvamgujomn xiimyzbbnp (pcfovwklru, gdazluowab - gfcbpcvjke) View more