Delving into the Latest Updates on Darinaparsin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Darinaparsin (JAN/USAN), DMAs(III)G, SGLU

+ [11]

Target

Reactive oxygen species

Mechanism

Reactive oxygen species stimulants, Apoptosis stimulants, Cell division inhibitors

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

Peripheral T-Cell Lymphoma

Inactive Indication

Advanced cancerAdvanced Hepatocellular CarcinomaAdvanced Malignant Solid Neoplasm+ [7]

Originator Organization

Solasia Pharma KK

Active Organization

Nippon Kayaku Co., Ltd.

Solasia Pharma KK

Inactive Organization

Alaunos Therapeutics, Inc.

Meiji Seika Pharma Co., Ltd.

Drug Highest PhaseApproved

First Approval Date

JP (20 Jun 2022),

Peripheral T-Cell Lymphoma

RegulationOrphan Drug (EU), Orphan Drug (US)

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Structure

Molecular FormulaC12H22AsN3O6S

InChIKeyJGDXFQORBMPJGR-YUMQZZPRSA-N

CAS Registry69819-86-9

Dimethylarsenate [DMAs(V)] can be produced by some soil microorganisms through methylation of inorganic arsenic (As), especially in anoxic paddy soils. DMAs(V) is more phytotoxic than inorganic As and can cause the physiological disorder straighthead disease in rice. Rice cultivars vary widely in the resistance to DMAs(V), but the mechanism remains elusive. Here, we investigated the differences in DMAs(V) uptake, translocation, and reduction to dimethylarsenite [DMAs(III)], as well as the effects on the metabolome, between two rice cultivars Mars and Zhe733. We found that Mars was 11-times more resistant to DMAs(V) than Zhe733. Mars accumulated more DMAs(V) in the roots, whereas Zhe733 translocated more DMAs(V) to the shoots and reduced more DMAs(V) to DMAs(III). DMAs(III) was more toxic than DMAs(V). Using heterologous expression and in vitro enzyme assays, we showed that the glutathione-S-transferases OsGSTU17 and OsGSTU50 were able to reduce DMAs(V) to DMAs(III). The expression levels of OsGSTU17 and OsGSTU50 were higher in the shoot of Zhe733 compared to Mars. Metabolomic analysis in rice shoots showed that glutathione (GSH) metabolism was perturbed by DMAs(V) toxicity in Zhe733. Application of exogenous GSH significantly alleviated the toxicity of DMAs(V) in Zhe733. Taken together, the results suggest that Mars is more resistant to DMAs(V) than Zhe733 because of a lower root-to-shoot translocation and a smaller capacity to reduce DMAs(V) to DMAs(III).

02 Jan 2024·Leukemia & lymphoma

Efficacy of darinaparsin for EBV-associated B-cell lymphoma in a heavily treated elderly patient with angioimmunoblastic T-cell lymphoma: a case report

Article

Author: Uehara, Atsushi ; Oura, Mitsuaki ; Matsue, Kosei ; Ikeda, Daisuke ; Takeuchi, Masami ; Tabata, Rikako ; Narita, Kentaro

12 Sep 2023·Blood advances

Darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma: results of an Asian phase 2 study

Article

Author: Nagahama, Fumiko ; Terui, Yasuhito ; Kwong, Yok-Lam ; Tobinai, Kensei ; Uchida, Toshiki ; Yamamoto, Kazuhito ; Sonehara, Yusuke ; Nagai, Hirokazu ; Yoon, Dok-Hyun ; Tien, Hwei-Fang ; Ando, Kiyoshi ; Negoro, Eiju ; Izutsu, Koji ; Suehiro, Youko ; Fukuhara, Noriko ; Kang, Hye Jin ; Nakajima, Hideaki ; Kim, Won-Seog ; Ko, Po-Shen

Abstract:

Darinaparsin is a novel organic arsenical compound of dimethylated arsenic conjugated to glutathione, with antitumor activity and a mechanism of action markedly different from other available agents. This phase 2, nonrandomized, single-arm, open-label study evaluated the efficacy and safety of intravenous darinaparsin (300 mg/m2 over 1 hour, once daily for 5 consecutive days, per 21-day cycle) and its pharmacokinetics at multiple doses in 65 Asian patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The primary end point was the overall response rate (ORR). The ORR based on central assessment was 19.3% (90% confidence interval, 11.2-29.9), which was significantly higher than the predefined threshold of 10% (P = .024). The ORR was 16.2% in patients with PTCL–not otherwise specified and 29.4% in patients with angioimmunoblastic T-cell lymphoma. Tumor size decreased in 62.3% of patients. Treatment-emergent adverse events (TEAEs) were observed in 98.5% of patients. Grade ≥3 TEAEs with an incidence rate of ≥5% included anemia (15.4%), thrombocytopenia (13.8%), neutropenia (12.3%), leukopenia (9.2%), lymphopenia (9.2%), and hypertension (6.2%). Darinaparsin is effective and well tolerated, with TEAEs that were clinically acceptable and manageable with symptomatic treatment and dose reductions. This trial was registered at www.clinicaltrials.gov as #NCT02653976.

1

News (Medical) associated with Darinaparsin

05 Jul 2022

·www.prnewswire.com

Brand Institute Partners on Brand Name Development for Treatment of Relapsed or Refractor Peripheral T-Cell Lymphoma Now Approved by Ministry of Health, Labour and Welfare (Japan)

MIAMI, July 5, 2022 /PRNewswire/ -- Brand Institute is proud to announce its work with Solasia Pharma K.K. ("Solasia") in developing the brand name DARVIAS®. DARVIAS®, an organoarsenic compound with anticancer activity, is a novel mitochondrial-targeted agent being developed for the treatment of various hematologic and solid tumors. DARVIAS® provokes cell cycle arrest and apoptosis through disruption of mitochondrial functions and increased production of reactive oxygen species in tumor cells. DARVIAS® is expected to exert an anticancer effect by inducing cell cycle arrest and apoptosis. DARVIAS® has been approved for relapsed or refractory Peripheral T-Cell Lymphoma by Japan's Ministry of Health, Labour and Welfare (MHLW). Japan is the first country in the world where DARVIAS® has been approved. DARVIAS® has been granted orphan drug designation in the US and EU. "The entire Brand Institute and Drug Safety Institute team congratulates Solasia on the MHLW approval of the DARVIAS injection," said Brand Institute's Chairman and C.E.O., James L. Dettore. About Brand Institute and our wholly owned regulatory subsidiary, Drug Safety Institute Brand Institute is the global leader in pharmaceutical and healthcare-related name development, with a portfolio of over 3,800 marketed healthcare brand names, 1,200 USAN/INN nonproprietary names for 1,100 clients. The company partners on over 75% of pharmaceutical brand and nonproprietary name approvals globally every year with healthcare manufacturers. Drug Safety Institute is composed of former naming regulatory officials from global government health agencies, including Food and Drug Administration (FDA), European Medicines Agency (EMA), Health Canada (HC), American Medical Association (AMA), and the World Health Organization (WHO). These regulatory experts co-authored the name review guidelines while with their respective agencies, with many responsible for ultimately approving (or rejecting) brand name applications. Now working for a private company, these professionals provide Brand Institute's clients with industry-leading guidance pertaining to drug name safety (i.e., preventing medication errors), packaging, and labeling. Contact: James Dettore Chairman & C.E.O. [email protected] SOURCE Brand Institute, Inc.

Orphan Drug

100 Deals associated with Darinaparsin

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External Link

KEGG	Wiki	ATC	Drug Bank
D08898	-	-	DB06179

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Peripheral T-Cell Lymphoma	JP	Solasia Pharma KK	20 Jun 2022
Peripheral T-Cell Lymphoma	JP	Nippon Kayaku Co., Ltd.	20 Jun 2022

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Hepatocellular Carcinoma	Phase 2	US	Alaunos Therapeutics, Inc.	01 Jan 2007
Bone Marrow Neoplasms	Phase 2	US	Alaunos Therapeutics, Inc.	01 Dec 2006
Multiple Myeloma	Phase 2	CA	Alaunos Therapeutics, Inc.	01 Jan 2006
Hepatocellular Carcinoma	Phase 2	-	Meiji Seika Pharma Co., Ltd.	-
Lymphoma	Phase 1	-	Alaunos Therapeutics, Inc.	01 Jun 2010
Advanced cancer	Phase 1	US	Alaunos Therapeutics, Inc.	01 Aug 2007
Advanced Malignant Solid Neoplasm	Phase 1	US	Alaunos Therapeutics, Inc.	01 May 2005
Myelodysplastic Syndromes	Phase 1	US	Alaunos Therapeutics, Inc.	01 May 2005
Myeloproliferative Disorders	Phase 1	US	Alaunos Therapeutics, Inc.	01 May 2005
Recurrent Acute Leukemia	Phase 1	US	Alaunos Therapeutics, Inc.	01 May 2005

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02653976 (CTgov)	Phase 2	Peripheral T-Cell Lymphoma	67	SP-02L (darinaparsin for injection)	obgopkipyi(uhkcpkjqat) = szlpbgvwje myohxurojm (pehmcuvqeo, ccuhpgnljj - eosmevtfpa) View more	-	26 Jan 2024
NCT02653976 (Pubmed)	Phase 2	Peripheral T-Cell Lymphoma	65	Darinaparsin	cbgcbtdefu(ufclhqbauu) = qorftajtbi gbwvebtobv (wpjrrfuzrd, 11.2 - 29.9)	Positive	20 Jan 2023
NCT01689220 \| NCT01435863 (Pubmed \| Jpn J Clin Oncol) Manual	Phase 1	Peripheral T-Cell Lymphoma	23	Darinaparsin	ghcztodsrh(cvpixxdubw) = lymphopenia (9%), neutropenia (9%) and thrombocytopenia (9%) xvltucfean (yylsrnnfwu )	Positive	08 Feb 2021
NCT02653976 (Biospace) Manual	Phase 2	Peripheral T-Cell Lymphoma	-	DARINAPARSIN	ymmpcfgtpk(ifewwnbmga) = reach twkvrblxgv (jekmkssvxy ) View more	Positive	15 Jun 2020
NCT00509782 (Pubmed \| Clin Cancer Res)	Phase 1	Solid tumor	47	Darinaparsin	yfgsqbvahs(kjxplqeqst) = iohczehpcn gsurhzvgrp (zbocepwdum ) View more	-	15 Jul 2009
ASCO2009	Phase 2	Advanced Hepatocellular Carcinoma	15	Darinaparsin	ltpmavzybu(rrsaiimhdk) = pxyemjknmc kxiqjawhck (wqumfclvxs, 93 - 227) View more	Negative	20 May 2009
ASCO2007	Phase 1/2	Multiple Myeloma	19	ZIO-101 daily for 5 consecutive d every 4 w	lpqwevlaha(qopigntllq) = transient confusion /ataxia fuoizbmaik (yklztveqql )	-	20 Jun 2007
ASCO2007	Phase 1	HR-positive/HER2-low Solid Tumors	34	ZIO-101	kvyreyslus(unkwhdczwf) = transient confusion, and ataxia pcnvkjhppq (syqotlrczk ) View more	-	20 Jun 2007
Tandem Meetings ASTCT and CIBMTR2007	Phase 1/2	Multiple Myeloma	13	ZIO-101	qvsjrllgsj(ktjufgxdot) = kfcexgxauf chjnokjjlm (mgcqqbnszo, 0.8) View more	Positive	01 Feb 2007
ASCO2006	Phase 1	Hematologic Neoplasms	8	ZIO-101	nhyzptjueh(sjdapwmdvm) = sijczetjyv rndwfxwfnk (jljseexvso ) View more	-	20 Jun 2006