Delving into the Latest Updates on Sodium metaarsenite(Komipharm) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

KOMINOX, PANAPHIX, Sodium metaarsenite

+ [3]

Target

Telomerase

Mechanism

Telomerase inhibitors

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases

Active Indication

Hepatocellular CarcinomaLung Cancer

Inactive Indication

Bile Duct NeoplasmsBrain CancerCancer Pain+ [5]

Originator Organization

Komipharm

Active Organization-

Inactive Organization

Komipharm International Co., Ltd.

University of Maryland Marlene and Stewart Greenebaum Cancer Center

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaAsHO2

InChIKeyXHTRYVMKFMUJLU-UHFFFAOYSA-N

CAS Registry13768-07-5

View All Structures (2)

Objective: The present study aimed to demonstrate the possible effects of increased 2-arachidonoylglycerol (2-AG) by applying the monoacylglycerol lipase inhibitor KML-29 on rats with ovarian ischemia-reperfusion (IR) model. Methods: Forty-eight female Wistar albino rats were divided into six groups. Group 1: Sham, Group 2: Ischemia, Group 3: IR, Group 4: IR + KML-29 (2 mg/kg), Group 5: IR + KML-29 (20 mg/kg), and Group 6: IR + vehicle (dimethyl sulfoxide). Three hours of ischemia followed by 3 h of reperfusion. Two different doses of KML-29 (2 and 10 mg/kg) were administered intraperitoneally in Groups 4 and 5, 30 min before reperfusion. Ovarian IR injury and ovarian reserve were evaluated histopathological and by using nuclear factor (NF)-κB, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, superoxide dismutase, glutathione peroxidase pre-/postoperative blood antimullerian hormone, and inhibin B. Results: In the KML-1 and KML-2 groups, this damage was significantly reduced compared to the ischemia group. NF-κB, IL-1β, TNF-α, and TGF-β1 immunoreactivities increased statistically significantly in the ischemia group compared to the control group (p<0.001). Immunoreactivities of these proteins were significantly decreased in the KML-1 and KML-2 groups (p<0.001). It was observed that the number of these apoptotic cells decreased significantly in the KML-1 and KML-2 groups compared to the ischemia group (p<0.001). The postoperative inhibin level showed a significant decrease in the ischemia group compared to the sham group, while a significant increase was observed in the KML-1 and KML-2 groups compared to the ischemia group. Conclusion: It was seen that anti-inflammatory, antioxidant, and antiapoptotic activity was formed, and the ovarian reserve was preserved with 2-AG in ovarian IR damage. The protective effect of endocannabinoids on the ovaries may create a promising new treatment strategy for many pathologies that will affect the ovarian reserve.

01 Sep 2020·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Phase I clinical trial of KML001 monotherapy in patients with advanced solid tumors

Q2 · MEDICINE

Article

Author: Park, Young Suk ; Lee, Jeeyun ; Ahn, Jin Seok ; Sun, Jong Mu ; Kim, Jungryul ; Ahn, Myung-Ju ; Park, Joon Oh ; Kim, Seokuee ; Han, RaeO ; Kim, Sujong ; Lim, Ho Yeong ; Kang, Won Ki

BACKGROUNDWe evaluated the tolerability, pharmacokinetics (PK) and preliminary efficacy of KML001, an oral trivalent arsenical, as a monotherapy in patients with advanced solid tumors.RESEARCH DESIGN AND METHODSWith a standard 3 + 3 design for dose-escalation stage, the planned dose levels of KML001 were 5, 7.5, 10, 12.5, and 15 mg/day for 28 days. Once the maximum tolerated dose was determined, 22 subjects were additionally enrolled for dose-expansion stage. PK analysis was performed in the 5, 10, and 15 mg/day cohort at the dose-escalation stage and also at the dose-expansion stage. Moreover, response was assessed using the standard RECIST 1.1.RESULTSA total of 45 Korean subjects were enrolled. No DLT was reported at the dose-escalation stage. Three DLTs, two cases of prolonged QTc interval and one of neutropenia, were reported in the 12.5 mg/day cohort at the dose-expansion stage. Higher total daily doses up to 12.5 mg/day of KML001 resulted in higher trough plasma concentrations. Among the 18 subjects who completed 2 cycles of therapy, 15 had progressive disease and 3 had stable disease.CONCLUSIONSDoses equal to or greater than 10 mg/day KML001 alone were tolerable and produced plasma concentrations higher than biologically relevant targets.

01 Feb 2019·Hepatobiliary & Pancreatic Diseases InternationalQ3 · MEDICINE

KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

Q3 · MEDICINE

Article

Author: Bang, Seungmin ; Jo, Jung Hyun ; Park, Seung Woo ; Lee, Hee Seung ; Chung, Moon Jae ; Park, Jeong Youp ; Kang, Huapyong ; Song, Si Young

BACKGROUNDSodium meta-arsenite (NaAsO₂, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer (BTC) resistant to gemcitabine-based chemotherapy.METHODSForty-four patients (21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status (PS) 0-2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001 (7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT.RESULTSAfter an average of 1.5 months of treatment (range: 0.5-10.0), 3 patients (6.8%) obtained progression-free status, 23 patients (52.3%) had disease progression, and 18 patients (40.9%) dropped out before evaluation. One patient (2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients (47.6%). Nine patients (20.5%) experienced grade-3 adverse events (AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation (11/44, 25%) and anemia (10/44, 22.7%). KML001 was discontinued in six patients (13.6%) due to AEs, including liver toxicity (n = 3), QTc prolongation (n = 2), and abdominal pain (n = 1).CONCLUSIONSKML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

100 Deals associated with Sodium metaarsenite(Komipharm)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Phase 2	-	-	-
Lung Cancer	Phase 2	-	-	-
Brain Cancer	Phase 1	KR	Komipharm International Co., Ltd.	23 Oct 2020
Non-Small Cell Lung Cancer	Phase 1	US	University of Maryland Marlene and Stewart Greenebaum Cancer Center	-
Glioblastoma	Preclinical	AU	Komipharm International Co., Ltd.	28 Nov 2019
Liver Cancer	Preclinical	KR	Komipharm International Co., Ltd.	03 Jul 2016
Bile Duct Neoplasms	Preclinical	KR	Komipharm International Co., Ltd.	09 Jun 2016
Prostatic Cancer	Preclinical	KR	Komipharm International Co., Ltd.	30 May 2016
Cancer Pain	Preclinical	AU	Komipharm International Co., Ltd.	06 Oct 2015
Non-Hodgkin Lymphoma	Preclinical	KR	Komipharm International Co., Ltd.	13 Feb 2015