Delving into the Latest Updates on Albaconazole with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Albaconazole (USAN/INN)

+ [1]

Target

fungal CYP51A1

Mechanism

fungal CYP51A1 inhibitors(Fungal CYP51A1 inhibitors)

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases+ [1]

Active Indication-

Inactive Indication

Candidiasis, VulvovaginalChagas DiseaseMycoses+ [2]

Originator Organization

Palau Pharma SA

Active Organization-

Inactive Organization

GSK PlcActavis A/S

Palau Pharma SA

+ [1]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC20H16ClF2N5O2

InChIKeyUHIXWHUVLCAJQL-MPBGBICISA-N

CAS Registry187949-02-6

Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of immunoglobulin (Ig)A in maintaining gut homeostasis and preventing inflammation has been well established. Our earlier work demonstrated that the marginal zone and B1 cell-specific protein (MZB1) promotes gut IgA secretion and its absence results in pronounced dextran sulfate sodium salt (DSS)-induced colitis. In the present study, we explored the role of MZB1 in CRC development using the azoxymethane (AOM)/DSS-induced CRC model. We observed an increase in both the number and size of the tumor nodules in Mzb1^-/- mice compared with Mzb1^+/+ mice. The increase in CRC development and progression in Mzb1^-/- mice was associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation. Oral administration of the monoclonal IgA, W27, alleviated both the gut inflammation and AOM/DSS-induced CRC. Notably, cohousing Mzb1^+/+ and Mzb1^-/- mice from the 10th day after birth led to similar CRC development. Our findings underscore the pivotal role of MZB1-mediated IgA secretion in suppressing the onset and progression of CRC triggered by gut inflammation. Moreover, our study highlights the profound impact of microbiota composition, modulated by gut IgA levels, on gut inflammation. Nonetheless, establishing a direct correlation between the severity of colitis and subsequent CRC development and the presence or absence of a particular microbiota is challenging.

25 Apr 2024·Journal of Medicinal Chemistry

Discovery of a Novel Potent Tetrazole Antifungal Candidate with High Selectivity and Broad Spectrum

Article

Author: Wang, Ting ; Xie, Fei ; Ding, Zichao ; Yan, Lan ; Bao, Junhe ; Zhang, Dazhi ; Wang, Ruina ; Ni, Tingjunhong ; Jiang, Yuanying ; Chi, Xiaochen ; Hao, Yumeng ; Li, Liping

Thirty-one novel albaconazole derivatives were designed and synthesized based on our previous work. All compounds exhibited potent in vitro antifungal activities against seven pathogenic fungi. Among them, tetrazole compound D2 was the most potent antifungal with MIC values of <0.008, <0.008, and 2 μg/mL against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, respectively, the three most common and critical priority pathogenic fungi. In addition, compound D2 also exhibited potent activity against fluconazole-resistant C. auris isolates. Notably, compound D2 showed a lower inhibitory activity in vitro against human CYP450 enzymes as well as a lower inhibitory effect on the hERG K⁺ channel, indicating a low risk of drug-drug interactions and QT prolongation. Moreover, with improved pharmacokinetic profiles, compound D2 showed better in vivo efficacy than albaconazole at reducing fungal burden and extending the survival of C. albicans-infected mice. Taken together, compound D2 will be further investigated as a promising candidate.

01 Mar 2022·European Journal of Medicinal ChemistryQ1 · MEDICINE

Synthetic approaches and structural diversity of triazolylbutanols derived from voriconazole in the antifungal drug development

Q1 · MEDICINE

Review

Author: Emami, Saeed ; Saednia, Shahnaz ; Ghobadi, Elham

Voriconazole (VCZ) was the first approved triazole antifungal drug with 1-(1H-1,2,4-triazol-1-yl)butan-2-ol substructure. This drug showed a broad spectrum of activity, especially against yeasts and molds, and opened a new avenue toward the novel class of systemic antifungal agents. Modification of 2-fluoropyrimidine in the side chain of VCZ resulted in a newer generation of triazolylbutanols including efinaconazole, albaconazole, ravuconazole, and isavuconazole with the favorable antifungal spectrum, enhanced pharmacokinetic properties, and tolerable toxicity profiles. Due to the importance of triazolylbutanols in the discovery and development of new antifungal agents, in this review we have focused on the synthetic approaches and structural diversity of triazolylbutanols derived from voriconazole. This comprehensive review provides highlighting scope for medicinal chemists for the design, synthesis and development of novel potential antifungal drugs having better activity, pharmacokinetic property and toxicity profile.

100 Deals associated with Albaconazole

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External Link

KEGG	Wiki	ATC	Drug Bank
D09702	Albaconazole	-	DB12073

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Onychomycosis	Phase 2	CA	GSK Plc	16 Jul 2008
Onychomycosis	Phase 2	US	GSK Plc	16 Jul 2008
Onychomycosis	Phase 2	IS	GSK Plc	16 Jul 2008
Tinea Pedis	Phase 2	US	GSK Plc	01 Jul 2007
Tinea Pedis	Phase 2	AU	GSK Plc	01 Jul 2007
Candidiasis, Vulvovaginal	Phase 2	-	Grupo J Uriach SL	01 Jun 2004
Chagas Disease	Phase 2	ES	-	-
Mycoses	Phase 2	-	Palau Pharma SA	-
Mycoses	Phase 2	-	Actavis A/S	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00730405 (CTgov)	Phase 2	Onychomycosis	582	Albaconazole (Albaconazole 400 mg (36 Weeks) Oral Weekly)	izplzbujfw(dhghozhkeo) = iohyxfvjhv vtfijsisgu (gaykxlegdb, gtbswkcota - haladoypzo) View more	-	07 Feb 2018
				Albaconazole (Albaconazole 400 mg (24 Weeks) Oral Weekly)	izplzbujfw(dhghozhkeo) = njyyrjlfnx vtfijsisgu (gaykxlegdb, mgpsbsovzl - xozwaqfgui) View more