iKIX1

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

iKIX1 是 Pdr1 依赖性基因激活。它使耐药光滑念珠菌在体外和播散性和泌尿道光滑念珠菌感染的动物模型中对唑类抗真菌药物重新敏感。

iKIX1 is an Pdr1-dependent gene activation. It re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection.

iKIX1 (10-20 μg/ml)?inhibits cell growth in a concentration-dependent manner in the presence of 5 μM ketoconazole (KET) in HepG2 cells.FP titration curve showing the interaction of?CgGal11A KIX domain with?CgPdr1 AD30 fitted to a Kd?of 319.7 nM.?iKIX1?competes out?CgPdr1 AD30 with an IC50 of 190.2 μM . In vitro?binding studies, iKIX1 reveals that the Kd of the?CgPdr1 activation domain (AD) for the?CgGal11A KIX domain is 0.32 μM and the apparent Ki for?iKIX1?is 18 μM.iKIX1 (0-50 μM) inhibits Ketoconazole (KET)-induced upregulation of luciferase activity in a dose-responsive manner in a?Sc pdr1Δpdr3Δ?strain containing plasmid-borne?CgPDR1?and 3XPDRE-luciferase.A chromatin immunoprecipitation (ChIP) assay is used to examine Gal11/Med15 recruitment to Pdr1-regulated target genes in?S. cerevisiae. Ketoconazole induces Gal11/Med15 rapidly recruited to the promoters of the Pdr1 target genes?PDR5?and?SNQ2. iKIX1 abrogates Ketoconazole-induced recruitment of Gal11/Med15 and strongly inhibits azole-induced transcription of?ScPdr1 target genes. iKIX1?(20 μM) has an effect on the transcription of?C. glabrata?Pdr1-regulated genes involved in drug efflux and MDR (CgCDR1, CgCDR2?and?CgYOR1).?iKIX1?alone does not significantly affect Pdr1-target gene induction. But pre-treatment with iKIX1?reduces ketoconazole-induced CgPdr1 up-regulation in a durable and concentration-dependent manner. In RNA sequencing (RNA-Seq) assay of a?C. glabrata SFY114 (PDR1?wild-type) strain.?Azole up-regulates Pdr1-dependent genes in both yeasts, such as the drug efflux pumps?ScPDR5?and?CgCDR1i. KIX1?combines azole strongly blunts expression of many azole-activated and Pdr1-dependent genes in both?S.cerevisiae?and?C. glabrata, but iKIX1?alone affects very different sets of genes in?S.cerevisiae?and?C. glabrata. And then iKIX1?does not significantly alter the expression of?PDR1?or?GAL11/MED15 affects very different sets of genes in?S.cerevisiae and?C. glabrata. iKIX1?(0-150 μM) restores the efficacy of azoles towards?CgPDR1?gain-of-function mutants. It restores azole-sensitivity to?PDR1?gain-of-function mutant strains in a concentration-dependent manner.

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Microbiology/Virology

Antifungal

Antifungal

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656222-54-7

303.16

C10H8Cl2N4OS

>98% (HPLC)

In Vitro:?DMSO : 83.33 mg/mL (274.86 mM)

Clc1ccc(NC(=S)NNC(=O)CC#N)cc1Cl

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(-20℃)

With Ice Pack

≥ 2 years