ABSTRACTTrichophyton indotineae is an emerging dermatophyte that causes severe tinea corporis and tinea cruris. Numerous cases of terbinafine- and azole-recalcitrant T. indotineae -related dermatophytosis have been observed in India over the past decade, and cases are now being recorded worldwide. Whole genome sequencing of three azole-resistant strains revealed a variable number of repeats of a 2,404 base pair (bp) sequence encoding TinCYP51B in tandem specifically at the CYP51B locus position. However, many other resistant strains (itraconazole MIC ≥0.25 µg/mL; voriconazole MIC ≥0.25 µg/mL) did not contain such duplications. Whole-genome sequencing of three of these strains revealed a variable number of 7,374 bp tandem repeat blocks harboring TinCYP51B . Consequently, two types of T. indotineae azole-resistant strains were found to host TinCYP51B in tandem sequences (type I with 2,404 bp TinCYP51B blocks and type II with 7,374 bp TinCYP51B blocks). Using the CRISPR/Cas9 genome-editing tool, the copy number of TinCYP51B within the genome of types I and II strains was brought back to a single copy. The azole susceptibility of these modified strains was similar to that of strains without TinCYP51B duplication, showing that azole resistance in T. indotineae strains is mediated by one of two types of TinCYP51B amplification. Type II strains were prevalent among 32 resistant strains analyzed using a rapid and reliable PCR test.

01 Oct 2023·Mycopathologia

Antifungal Efficacy of Luliconazole in an Experimental Rabbit Model of Fungal Keratitis Caused by Fusarium solani.

Article

Author: Ishino, Tomoko ; Arimoto, Sho ; Suzuki, Takashi ; Todokoro, Daisuke ; Inagaki, Katsuhiro ; Makimura, Koichi

Fungal keratitis is a corneal fungal infection that potentially leads to blindness and is mainly caused by filamentous fungi, such as Fusarium, with limited drug options available, such as natamycin and voriconazole. Therefore, this study aimed to evaluate the therapeutic effects of the imidazole antifungal drug-luliconazole-using a rabbit experimental model of fungal keratitis caused by Fusarium solani, which is the dominant causative agent of fungal keratitis. F. solani was inoculated into rabbit corneas. luliconazole 1% suspension or natamycin 5% eye drops were administered four times a day (N = 6 for each group) 3 days after inoculation. Signs were scored up to 14 days after inoculation to evaluate the efficacy of the drugs. Compared with the peak mean sign scores of the placebo control group, there was a significant decrease in the mean sign scores of both the treatment groups (P < 0.05). Sign score trends were similar between the two treatment groups. In conclusion, luliconazole demonstrated therapeutic efficacy comparable to that of natamycin in treating experimental fungal keratitis. This suggests that luliconazole can be a novel therapeutic agent for human fungal keratitis.

04 Mar 2021·Medical MycologyQ3 · MEDICINE

A comparative study between two antifungal agents, Luliconazole and Efinaconazole, of their preventive effects in a Trichophyton-infected guinea pig onychomycosis model

Q3 · MEDICINE

Article

Author: Hirakawa, Satoko ; Nakamura, Akihiro ; Nagai, Hiroaki ; Inagaki, Katsuhiro

AbstractAn efficacious period of two topical antifungal drugs was compared in a Trichophyton mentagrophytes-infected onychomycosis model in guinea pigs treated with antifungal drugs prior to infection. Luliconazole 5% (LLCZ) and efinaconazole 10% (EFCZ) test solutions were applied to the animals’ nails once daily for 2 weeks followed by a nontreatment period of 2, 4, and 8 weeks. After each nontreatment period, the nails were artificially infected by the fungus. Drug efficacy was quantitatively evaluated by qPCR and histopathological examination of the nails collected following a 4-week post-infection period. The fungal infection was confirmed in the untreated group. Both LLCZ and EFCZ prevented fungal infection in the treated groups with the nontreatment period of 2 weeks. After the nontreatment period of 4 weeks, no infection was observed in the LLCZ-treated group; however, infection into the nail surface and fungal invasion into the nail bed were observed in the EFCZ-treated group. After the nontreatment period of 8 weeks, fungi were found in the nail surface and nail bed in some nails treated with EFCZ; however, no infection was observed in the nail bed of the LLCZ-treated group. The results suggest that LLCZ possesses longer-lasting antifungal effect in nails of the guinea pigs than EFCZ, and that this animal model could be useful for translational research between preclinical and clinical studies to evaluate the pharmacological efficacy of antifungal drugs to treat onychomycosis. This experimentally shown longer-lasting preventive effects of LLCZ could also decrease the likelihoods of onychomycosis recurrence clinically.

News (Medical) associated with Nihon Nohyaku Co., Ltd.

10 Sep 2015

·www.bioportfolio.com

Onychomycosis (Tinea Unguium) - Pipeline Review, H2 2015

Recently added to the BioPortfolio report store, Onychomycosis (Tinea Unguium) - Pipeline Review, H2 2015 is a new report from Global Markets Direct published on 2015-07-30. This 68-page report is available in PDF from $2000. Onychomycosis (Tinea Unguium) - Pipeline Review, H2 2015 Summary Global Markets Direct’s, ‘Onychomycosis (Tinea Unguium) - Pipeline Review, H2 2015’, provides an overview of the Onychomycosis (Tinea Unguium)’s therapeutic pipeline. This report provides comprehensive information on the therapeutic development for Onychomycosis (Tinea Unguium), complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA) and molecule type, along with latest updates, and featured news and press releases. It also reviews key players involved in the therapeutic development for Onychomycosis (Tinea Unguium) and special features on late-stage and discontinued projects. Global Markets Direct’s report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from Global Markets Direct’s proprietary databases, Company/University websites, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources, put together by Global Markets Direct’s team. Drug profiles/records featured in the report undergoes periodic updation following a stringent set of processes that ensures that all the profiles are updated with the latest set of information. Additionally, processes including live news & deals tracking, browser based alert-box and clinical trials registries tracking ensure that the most recent developments are captured on a real time basis. The report enhances decision making capabilities and help to create effective counter strategies to gain competitive advantage. It strengthens R&D pipelines by identifying new targets and MOAs to produce first-in-class and best-in-class products. Note*: Certain sections in the report may be removed or altered based on the availability and relevance of data for the indicated disease. Scope - The report provides a snapshot of the global therapeutic landscape of Onychomycosis (Tinea Unguium) - The report reviews key pipeline products under drug profile section which includes, product description, MoA and R&D brief, licensing and collaboration details & other developmental activities - The report reviews key players involved in the therapeutics development for Onychomycosis (Tinea Unguium) and enlists all their major and minor projects - The report summarizes all the dormant and discontinued pipeline projects - A review of the Onychomycosis (Tinea Unguium) products under development by companies and universities/research institutes based on information derived from company and industry-specific sources - Pipeline products coverage based on various stages of development ranging from pre-registration till discovery and undisclosed stages - A detailed assessment of monotherapy and combination therapy pipeline projects - Coverage of the Onychomycosis (Tinea Unguium) pipeline on the basis of target, MoA, route of administration and molecule type - Latest news and deals relating related to pipeline products Reasons to buy - Provides strategically significant competitor information, analysis, and insights to formulate effective R&D development strategies - Identify emerging players with potentially strong product portfolio and create effective counter-strategies to gain competitive advantage … Table of Contents Table of Contents 2 List of Tables 5 List of Figures 6 Introduction 7 Global Markets Direct Report Coverage 7 Onychomycosis (Tinea Unguium) Overview 8 Therapeutics Development 9 Pipeline Products for Onychomycosis (Tinea Unguium) - Overview 9 Pipeline Products for Onychomycosis (Tinea Unguium) - Comparative Analysis 10 Onychomycosis (Tinea Unguium) - Therapeutics under Development by Companies 11 Onychomycosis (Tinea Unguium) - Pipeline Products Glance 12 Clinical Stage Products 12 Early Stage Products 13 Unknown Stage Products 14 Onychomycosis (Tinea Unguium) - Products under Development by Companies 15 Onychomycosis (Tinea Unguium) - Companies Involved in Therapeutics Development 16 Anacor Pharmaceuticals, Inc. 16 Eisai Co., Ltd. 17 Helix BioMedix, Inc. 18 Hexima Limited 19 Meiji Seika Pharma Co., Ltd. 20 Moberg Pharma AB 21 NAL Pharmaceuticals Ltd. 22 Nihon Nohyaku Co., Ltd. 23 Novabiotics Limited 24 Nuvo Research Inc. 25 Viamet Pharmaceuticals, Inc. 26 Onychomycosis (Tinea Unguium) - Therapeutics Assessment 27 Assessment by Monotherapy Products 27 Assessment by Target 28 Assessment by Mechanism of Action 30 Assessment by Route of Administration 32 Assessment by Molecule Type 34 Drug Profiles 36 AN-2718 - Drug Profile 36 Product Description 36 Mechanism of Action 36 R&D Progress 36 E-1224 - Drug Profile 37 Product Description 37 Mechanism of Action 37 R&D Progress 37 ELS-160 - Drug Profile 39 Product Description 39 Mechanism of Action 39 R&D Progress 39 HB-1275 - Drug Profile 40 Product Description 40 Mechanism of Action 40 R&D Progress 40 HXP-124 - Drug Profile 41 Product Description 41 Mechanism of Action 41 R&D Progress 41 luliconazole - Drug Profile 42 Product Description 42 Mechanism of Action 42 R&D Progress 42 ME-1111 - Drug Profile 45 Product Description 45 Mechanism of Action 45 R&D Progress 45 NAL-3216 - Drug Profile 46 Product Description 46 Mechanism of Action 46 R&D Progress 46 NP-213 - Drug Profile 47 Product Description 47 Mechanism of Action 47 R&D Progress 47 terbinafine - Drug Profile 49 Product Description 49 Mechanism of Action 49 R&D Progress 49 terbinafine - Drug Profile 50 Product Description 50 Mechanism of Action 50 R&D Progress 50 VT-1161 - Drug Profile 51 Product Description 51 Mechanism of Action 51 R&D Progress 51 Onychomycosis (Tinea Unguium) - Recent Pipeline Updates 53 Onychomycosis (Tinea Unguium) - Dormant Projects 58 Onychomycosis (Tinea Unguium) - Discontinued Products 61 Onychomycosis (Tinea Unguium) - Product Development Milestones 62 Featured News & Press Releases 62 Mar 26, 2015: Moberg Pharma Announces Grant of EU Patent for MOB-015 Related to Topical… For more information open Onychomycosis (Tinea Unguium) - Pipeline Review, H2 2015. SKU: GMDHC6868IDB

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The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Luliconazole ( fungal CYP51A1 )	Tinea corporis More	Approved
Lanoconazole ( fungal CYP51A1 )	Tinea Pedis More	Approved
R-755 ( ACAT1 )	Atherosclerosis More	Preclinical
NRA-0161 ( D4 receptor )	Psychotic Disorders More	Discontinued
NRA-0544 ( D4 receptor )	Psychotic Disorders More	Discontinued

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