Delving into the Latest Updates on Mefuparib Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Mefuparib

Target

PARP1 x PARP2

Mechanism

PARP1 inhibitors(Poly (ADP-Ribose) polymerase 1 inhibitors), PARP2 inhibitors(Poly (ADP-Ribose) Polymerase 2 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [4]

Active Indication

Metastatic castration-resistant prostate cancerBile Duct NeoplasmsBreast Cancer+ [8]

Inactive Indication-

Originator Organization

Cisen Pharmaceutical Ltd.

Active Organization

Convalife (Shanghai) Co. Ltd.

Cisen Pharmaceutical Ltd.

Shanghai Institute of Materia Medica Chinese Academy of Sci

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationSpecial Review Project (CN), Orphan Drug (US)

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Structure/Sequence

Molecular FormulaC17H16ClFN2O2

InChIKeyGPFWTAVHQKERKY-UHFFFAOYSA-N

CAS Registry1449746-00-2

View All Structures (2)

This study aims to evaluate the efficacy of CVL218 in combination with Toripalimab injection/Sintilimab injection (Darbersol, Sintilimab) in the treatment of advanced solid tumors. It focuses on assessing the safety, tolerability, and pharmacokinetic profile of a three-drug combination regimen comprising albumin-bound paclitaxel injection (Kealil), paclitaxel injection (Taxol), and Fuquinitinib capsule (Aiutec, Fruquintinib).

Start Date10 Oct 2023

Sponsor / Collaborator

Fujian Cancer Hospital

CTR20190906

/ RecruitingPhase 1

CVL218在晚期实体瘤患者中的耐受性及药代动力学I期临床研究

[Translation] Phase I clinical study on the tolerability and pharmacokinetics of CVL218 in patients with advanced solid tumors

确定CVL218单次及多次口服给药在晚期肿瘤患者中的安全性和耐受性，探索限制性毒性（DLT）及最大耐受剂量（MTD），确定进一步临床研究的推荐剂量及给药方案。

[Translation]

Determine the safety and tolerability of single and multiple oral administrations of CVL218 in patients with advanced tumors, explore the limiting toxicity (DLT) and maximum tolerated dose (MTD), and determine the recommended dose and dosing regimen for further clinical studies.

Start Date16 Jul 2019

Sponsor / Collaborator

Cisen Pharmaceutical Ltd.

[+1]

100 Clinical Results associated with Mefuparib Hydrochloride

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100 Translational Medicine associated with Mefuparib Hydrochloride

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100 Patents (Medical) associated with Mefuparib Hydrochloride

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8

Literatures (Medical) associated with Mefuparib Hydrochloride

01 Dec 2022·Cancer Chemotherapy and Pharmacology

Absorption, distribution, metabolism, and excretion of [14C]Mefuparib (CVL218), a novel PARP1/2 inhibitor, in rats

Article

Author: Huan, Xia-Juan ; Li, Xin-Mei ; Liu, Meng-Ling ; Diao, Xing-Xing ; Shen, Xiao-Kun ; Yang, Chun-Hao ; Yang, Chen ; Zheng, Yuan-Dong ; Zhang, Yi-Fan

INTRODUCTIONMefuparib (CVL218) is a novel second-generation poly-ADP-ribose polymerase (PARP) inhibitor for cancer treatment. CVL218 can easily enter the brain. However, the transport mechanism by which CVL218 crosses the blood-brain barrier (BBB) is unknown.METHODS(1) [¹⁴C] CVL218 metabolism in rats was traced by a liquid scintillation counter and oxidative combustion. (2) Metabolic profiles and metabolites were identified by UHPLC-β-RAM/UHPLC-Fraction Collector and UHPLC-Q Exactive Plus MS. (3) The partition coefficient K_p,uu,brain value was simulated by two strategies. One strategy was using ACD and GastroPlus Software based on the results of intravenous administration pharmacokinetics and plasma protein-binding studies. The reliability was confirmed by comparison with another strategy (brain/plasma distribution study).RESULTS(1) Rapid drug elimination was observed 24 h after intragastric administration. The total cumulative excretion in urine and feces within 168 h accounted for 97.15% of the dose. The cumulative radioactive dose recovery in bile was 41.87% within 72 h. The drug-related substances were extensively distributed to the tissues within 48 h. (2) M8 was the major metabolite in plasma, urine, feces and bile. (3) CVL218 exhibited high brain protein-binding rate (88.16%). The K_p,uu,brain value (8.42) simulated by the simple software strategy was similar to that of the brain/plasma distribution study (7.01).CONCLUSIONSCVL218 is a fast-metabolizing drug and is mainly excreted in feces. The B/P ratio prediction and observation data for CVL218 were consistent. Furthermore, the K_p,uu,brain value indicated that penetration through the BBB might be mediated by uptake transporters.

01 Jul 2022·Advanced Biology

Phase Separation: “The Master Key” to Deciphering the Physiological and Pathological Functions of Cells

Review

Author: Zhu, Xiao ; Li, Xinming ; Li, Mingdong ; Lyu, Jianxin ; Wei, Chuzhong

AbstractPhase separation is a hot research field at present. It involves almost all aspects of cells and plays a significant role in cells, promising to be “a master key” in unlocking the mysteries of nature. In this review, the factors that affect phase separation are introduced, such as own component, electrostatic interaction, and chemical modification. Furthermore, the physiological roles of phase separation in cells, including molecules transport channel, gene expression and regulation, cellular division and differentiation, stress response, proteins refolding and degradation, cell connections, construction of skin barrier, and cell signals transmission, are highlighted. However, the disorder of phase separation leads to pathological condensates, which are associated with neurodegenerative diseases, tumors, and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This relationship is considered the potential target for developing corresponded drugs and therapy. Some drugs targeting phase separation have improved meaningful, such as tankyrase, lipoamide, oligonucleotides, elvitagravir, nilotinib, CVL218, PJ34. All in all, mystery phase separation provides a new viewpoint for researchers to explore cells, and is expected to solve many unknown phenomena in nature.

01 Feb 2022·Journal of Infection and Public HealthQ3 · MEDICINE

Covid-19 and Artificial Intelligence: Genome sequencing, drug development and vaccine discovery

Q3 · MEDICINE

ReviewOA

Author: Ibrahim, Nahla Khamis ; Abubaker Bagabir, Hala ; Abubaker Bagabir, Sali ; Hashem Ateeq, Raghdah

OBJECTIVESTo clarify the work done by using AI for identifying the genomic sequences, development of drugs and vaccines for COVID-19 and to recognize the advantages and challenges of using such technology.METHODSA non-systematic review was done. All articles published on Pub-Med, Medline, Google, and Google Scholar on AI or digital health regarding genomic sequencing, drug development, and vaccines of COVID-19 were scrutinized and summarized.RESULTSThe sequence of SARS- CoV-2 was identified with the help of AI. It can help also in the prompt identification of variants of concern (VOC) as delta strains and Omicron. Furthermore, there are many drugs applied with the help of AI. These drugs included Atazanavir, Remdesivir, Efavirenz, Ritonavir, and Dolutegravir, PARP1 inhibitors (Olaparib and CVL218 which is Mefuparib hydrochloride), Abacavir, Roflumilast, Almitrine, and Mesylate. Many vaccines were developed utilizing the new technology of bioinformatics, databases, immune-informatics, machine learning, and reverse vaccinology to the whole SARS-CoV-2 proteomes or the structural proteins. Examples of these vaccines are the messenger RNA and viral vector vaccines. AI provides cost-saving and agility. However, the challenges of its usage are the difficulty of collecting data, the internal and external validation, ethical consideration, therapeutic effect, and the time needed for clinical trials after drug approval. Moreover, there is a common problem in the deep learning (DL) model which is the shortage of interpretability.CONCLUSIONThe growth of AI techniques in health care opened a broad gate for discovering the genomic sequences of the COVID-19 virus and the VOC. AI helps also in the development of vaccines and drugs (including drug repurposing) to obtain potential preventive and therapeutic agents for controlling the COVID-19 pandemic.

100 Deals associated with Mefuparib Hydrochloride

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic castration-resistant prostate cancer	Phase 2	CN	Cisen Pharmaceutical Ltd.	21 Jun 2021
Metastatic castration-resistant prostate cancer	Phase 2	CN	Shanghai Institute of Materia Medica Chinese Academy of Sci	21 Jun 2021
Bile Duct Neoplasms	Phase 2	CN	Convalife (Shanghai) Co. Ltd.	-
Breast Cancer	Phase 2	CN	Convalife (Shanghai) Co. Ltd.	-
Pancreatic Cancer	Phase 2	CN	Convalife (Shanghai) Co. Ltd.	-
Prostatic Cancer	Phase 2	CN	Convalife (Shanghai) Co. Ltd.	-
Bladder Cancer	Phase 1	CN	Convalife (Shanghai) Co. Ltd.	-
Glioma	Phase 1	CN	Convalife (Shanghai) Co. Ltd.	-
Soft Tissue Sarcoma	Phase 1	CN	Convalife (Shanghai) Co. Ltd.	-
Triple Negative Breast Cancer	Phase 1	CN	Convalife (Shanghai) Co. Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CVL218 (SABCS2022)	Phase 1/2	Breast Cancer	-	CVL218	azapjoarlo(zawyzhrvlw) = fnguchezoh jurfopwtnm (cfjauzssgv ) View more	Positive	15 Feb 2022
				Olaparib	azapjoarlo(zawyzhrvlw) = ledqufftmc jurfopwtnm (cfjauzssgv ) View more