LICENSING OPPORTUNITY OVERVIEW

Antifungal agents targeting ERG25
Novel target molecules of the ergosterol synthesis pathway, a critical gene for Candida

Advantage and Core BenefitØØ
Ø

Resistant strains are unlikely to emerge due totargeting Candida ERD25 gene, which
deficiency results in lethality.
A novel mode of actin unlike azoles and otherexisting antifungal agents
Drug efficacy and species selectivity evaluation
system has been confirmed. Either way isavailable, lead optimization or new compoundscreening.

Background and Technology
There are a small variety of antifungal agents: azoles, which act by inhibiting ergosterol synthase, polyenes, which
act directly on ergosterol, echinocandins, which inhibit cell wall synthases, and fluoropyrimidines, which inhibit
nucleic acid synthesis. The emergence of resistant strains of fungi to all these systems has become a problem, anda new mechanism of action for antifungal drugs is required.
Inventors have shown that ERG25, an enzyme gene involved in the ergosterol synthesis pathway, plays animportant role in cholesterol uptake and cell membrane structure in fungi (Figure). Knockdown of ERG25 in Candida
glabrata prevented the plasma membrane localization of the sterol transport protein Aus1p and reduced the lethalityof infected mice.
The antifungal activity of 1181-0519: N-[(2E)-2-[(4-nitrophenyl) hydrazinylidene] propyl] acetamide, a known
inhibitor of sterol-C4-methyl monooxygenase encoded by ERG25, was evaluated. It showed antifungal activity(MIC) on the order of µM against several Candida species, including Candida auris. The results of 1181-0519
against knock-in yeast with human (hERG25) and Candida (CgERG25) forms of ERG25 showed no toxicity against
yeast strains with the human form, strongly suggesting that ERG25 is also a target with few potential adverse effects。

Data²²1181-0519, an inhibitor of ERG25, showed strong inhibitory activity against C. albicans, C. glabrata, C. auris,C. parapsilosis, and C. krusei, with a minimum inhibitory concentration (MIC) below 2 μM (Table below)
ERG25 identified as a killer gene of Candida glabrata as a target molecule with high fungicidal potential.

Patent & Publication
Patent pending (unpublished)https://doi.org/10.3390/jof9101035,
https://doi.org/10.3389/fcell.2022.820675

ResearcherDr. Hiroji Chibana (Medical Mycology Research Center, ChibaUniversity)

Expectations

MIC of 1181-0519 against Candida species.
StrainMIC (µM)
C. albicans SC5314
2
C. glabrata CBS 138
2
C. auris CBS 10913
1C. tropicalis CBS 94
16
C. parapsilosis CBS 604
1
C. krusei CBS 573
2We look forward to collaborating with companies interested in developing a new class of antifungal drugs throughjoint research on derivative development using 1181-0519 as the basic compound and screening for inhibitors ofERG25.
Contact
Ryo TAKAYANAGILicensing Associate
Tech Manage Corp.
ryo.takayanagi@tech-manage.co.jp

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