HSP90-IN-9

立即咨询

HSP90-IN-9

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

HSP90-IN-9 是一种有效的选择性HSP90抑制剂。HSP90-IN-9 以剂量依赖性方式显示杀真菌作用。HSP90-IN-9 与 FLC 联合用药可抑制真菌生物膜形成和真菌形态变化。HSP90-IN-9 可通过下调 ERG11、CDR1 和 CDR2 基因表达恢复对 FLC 的耐药性。

生物活性

HSP90-IN-9 is a potent and selectiveHSP90inhibitor. HSP90-IN-9 displays a fungicidal effect in a dose-dependent manner. HSP90-IN-9 inhibitsfungalbiofilm formation andfungalmorphological changes after being combined with FLC. HSP90-IN-9 recovers FLC resistance by down-regulating the expression of related genes (ERG11, CDR1 and CDR2)^[1].

IC₅₀& Target

HSP90

体外研究
(In Vitro)

HSP90-IN-9 (compound A17) (combined with FLC (2 μg/mL)) shows antifungal activities against the six FLC-resistantCandida albicans (C. albicans)strains (MIC₈₀s of 0.125 μg/mL instrain 901,strain 632,strain 100; MIC₈₀s of 0.25 μg/mL instrain 904,strain 103,strain311, respectively)^[1].
HSP90-IN-9 (24 h) shows low toxic to human cancer cells, human normal cells and the macrophage lineage (IC₅₀s is 13.12, 34.09, 17.45, 7.15, >50, 21.33, 17.05, 10.34 μM in A549, MCF-7, HEPG2, THLE-2, BEAS-2B, NIH-3T3, Raw264.7, BV-2 cells, respectively)^[1].
HSP90-IN-9 (32 μg/mL (combined with FLC (32 μg/mL)), 24 h) inhibits fungal biofilm formation and fungal morphological changes after being combined with FLC^[1].
HSP90-IN-9 (C. albicans (strain 904), 48 h) displays a fungicidal effect in a dose-dependent manner^[1].
HSP90-IN-9 (FLC + compound A17 (32 + 32 μg/mL)) recovers azole sensitivity in resistantC.albicansby down-regulating the expression of CYP51 (ERG11) efflux pump-related genes (CDR1 and CDR2)^[1].

Cell Cytotoxicity Assay^[1]

Cell Line:	A549, MCF-7, HEPG2, THLE-2, BEAS-2B, NIH-3T3, Raw264.7, BV-2 cells
Concentration:
Incubation Time:	24 h
Result:	Showed low toxic to human cancer cells, human normal cells and the macrophage lineage (IC₅₀s of 13.12, 34.09, 17.45, 7.15, >50, 21.33, 17.05, 10.34 μM in A549, MCF-7, HEPG2, THLE-2, BEAS-2B, NIH-3T3, Raw264.7, BV-2 cells, respectively).

RT-PCR^[1]

Cell Line:	Azole-resistantstrain 904
Concentration:	32 μg/mL (combined with FLC (32 μg/mL))
Incubation Time:	24 h
Result:	Inhibited fungal biofilm formation and fungal morphological changes after being combined with FLC.

体内研究
(In Vivo)

HSP90-IN-9 (10 mg/kg; i.v.) exhibits moderate pharmacokinetic properties in SD rats^[1].
HSP90-IN-9 (A17 (10 mg/kg)+FLC (1 mg/kg); i.p.; once a day for 5 days) exhibits potent in vivo antifungal efficacy by reducing the colonization and dissemination of fungi in tissue^[1].
Pharmacokinetic Parameters of HSP90-IN-9 in male Sprague-Dawley (SD) rats^[1].

dose (mg/kg)	T_1/2(h)	C₀(ng/mL)	AUC_(0-t)(h*ng/mL)	AUC_(0-∞)(h*ng/mL)	V_z(L/kg)	Cl (mL/min/kg)	MRT_(0-∞)(h)
10 mg/kg	1.26±0.31	4752.50±44.54	3005.15±35.59	3028.95±54.14	11.25±3.69	101.77±1.96	1.12±0.07

male Sprague-Dawley (SD) rats; 10 mg/kg; i.v.^[1]

Animal Model:	male Sprague-Dawley (SD) rats^[1]
Dosage:	10 mg/kg
Administration:	i.v.
Result:	Exhibited moderate pharmacokinetic properties in SD rats.

Animal Model:	female SD rats, 160-180 g (IFI rat model)^[1]
Dosage:	10 mg/kg, A17 (10 mg/kg)+FLC (1 mg/kg)
Administration:	i.p., once a day, 5 days
Result:	Exhibited potent in vivo antifungal efficacy by reducing the colonization and dissemination of fungi in tissue.

分子量

513.58

Formula

C₃₀H₃₁N₃O₅

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.