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概览

疾病领域	数量

神经系统疾病	2
免疫系统疾病	2

排名前五的药物类型	数量

小分子化药	5
蛋白水解靶向嵌合体（PROTAC）	1

排名前五的靶点	数量

T-type calcium channel(电压门控性T型钙通道家族)	2
CYP26A1 x CYP26B1	1

关联

12

项与 DermaXon LLC 相关的药物

DX-814

靶点-

作用机制-

在研机构

DermaXon LLC

原研机构

DermaXon LLC

在研适应症

自身炎症性疾病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

DX-465

靶点-

作用机制-

在研机构

DermaXon LLC

原研机构

DermaXon LLC

在研适应症

角化病 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

DX-416

靶点

T-type calcium channel

作用机制

T-type calcium channel阻滞剂

在研机构

DermaXon LLC

原研机构

DermaXon LLC

在研适应症

瘙痒 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 DermaXon LLC 相关的临床结果

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0 项与 DermaXon LLC 相关的专利（医药）

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5

项与 DermaXon LLC 相关的文献（医药）

2021-01-01·Neuro-Oncology Advances

A brain-penetrant microtubule-targeting agent that disrupts hallmarks of glioma tumorigenesis

Article

作者: Jung, Erik ; Diaz, Philippe ; Hamel, Ernest ; Stella, Nephi ; Xu, Cong ; Azorín, Daniel D ; Horne, Eric A ; Cimino, Patrick J ; Wordeman, Linda G ; Wagenbach, Michael ; Winkler, Frank ; Kumasaka, Debra ; Holland, Eric C ; Wageling, Nicholas B

AbstractBackgroundGlioma is sensitive to microtubule-targeting agents (MTAs), but most MTAs do not cross the blood brain barrier (BBB). To address this limitation, we developed the new chemical entity, ST-401, a brain-penetrant MTA.MethodsSynthesis of ST-401. Measures of MT assembly and dynamics. Cell proliferation and viability of patient-derived (PD) glioma in culture. Measure of tumor microtube (TM) parameters using immunofluorescence analysis and machine learning-based workflow. Pharmacokinetics (PK) and experimental toxicity in mice. In vivo antitumor activity in the RCAS/tv-a PDGFB-driven glioma (PDGFB-glioma) mouse model.ResultsWe discovered that ST-401 disrupts microtubule (MT) function through gentle and reverisible reduction in MT assembly that triggers mitotic delay and cell death in interphase. ST-401 inhibits the formation of TMs, MT-rich structures that connect glioma to a network that promotes resistance to DNA damage. PK analysis of ST-401 in mice shows brain penetration reaching antitumor concentrations, and in vivo testing of ST-401 in a xenograft flank tumor mouse model demonstrates significant antitumor activity and no over toxicity in mice. In the PDGFB-glioma mouse model, ST-401 enhances the therapeutic efficacies of temozolomide (TMZ) and radiation therapy (RT).ConclusionOur study identifies hallmarks of glioma tumorigenesis that are sensitive to MTAs and reports ST-401 as a promising chemical scaffold to develop brain-penetrant MTAs.

2020-12-01·Molecular Brain3区 · 医学

Cav3.2 T-type calcium channels control acute itch in mice

3区 · 医学

ArticleOA

作者: Zamponi, Gerald W ; Diaz, Philippe ; Gadotti, Vinicius M ; Budke, Dylan ; Kreitinger, Joanna M ; Wageling, Nicholas B

AbstractCav3.2 T-type calcium channels are important mediators of nociceptive signaling, but their roles in the transmission of itch remains poorly understood. Here we report a key involvement of these channels as key modulators of itch/pruritus-related behavior. We compared scratching behavior responses between wild type and Cav3.2 null mice in models of histamine- or chloroquine-induced itch. We also evaluated the effect of the T-type calcium channel blocker DX332 in male and female wild-type mice injected with either histamine or chloroquine. Cav3.2 null mice exhibited decreased scratching responses during both histamine- and chloroquine-induced acute itch. DX332 co-injected with the pruritogens inhibited scratching responses of male and female mice treated with either histamine or chloroquine. Altogether, our data provide strong evidence that Cav3.2 T-type channels exert an important role in modulating histamine-dependent and -independent itch transmission in the primary sensory afferent pathway, and highlight these channels as potential pharmacological targets to treat pruritus.

2019-11-11·Neuro-Oncology

DDIS-29. BRAIN-PENETRANT MICROTUBULE-TARGETING AGENT, ST-401, KILLS GLIOBLASTOMA THROUGH A NOVEL MECHANISM

作者: Stella, Nephi ; Diaz, Philippe ; Horne, Eric ; Uhlenbruck, Benjamin ; Deckwerth, Thomas ; Wordeman, Linda ; Gussio, Rick ; Holland, Eric ; Xu, Cong ; Hamel, Ernest ; Cimino, P J ; Vicente, Juan-Jesus ; Wagenbach, Michael

AbstractGlioblastomas are particularly sensitive to mitotic disruption when compared with nonmalignant cells and thus microtubule-targeting agents (MTA) represent promising therapeutics to treat patients with glioblastomas; but few such compounds pass the blood brain barrier. We developed a series of modified carbazoles, evaluated their anti-cancer activity in glioblastoma cells in culture and identified ST-401 as the most potent compound (IC50, 10 – 102 nM, depending on the cell line). Testing of ST-401 on the NCI 60 cancer cell panel indicated that its anti-tumor activity does not correlate with any of the compounds tested thus far through this platform but showed weak correlations for taxol (p=0.46) and vinblastine (p=0.34). Thus, ST-401 may kill cancer cells through a novel mechanism related to disruption of MT function. Biochemical analysis indicates that ST-401 binds to the colchicine site of tubulin and inhibits tubulin assembly. Real-time imaging of MT dynamics in cells in culture shows that ST-401 reduces MT assembly rates but in a reversible fashion. ST-401 potently blocks mitotic progression and triggers cell death in multiple glioblastoma lines in culture, including patient-derived glioblastomas of the proneural, mesenchymal and classical subtypes. We established the maximum tolerated dose (MTD) of ST-401 in mice (20 mg/kg/bdip) and found that its acute i.p. injection results in micromolar amounts of ST-401 in mouse brain. Using this treatment regimen, we found that ST-401 reduces tumor growth and doubles overall survival in a human tumor xenograft mouse model system. ST-401 also increases by 2-fold overall survival in the genetic RCAS-PDGF glioblastomas mouse model treated with standard care (radiation and Temodar® treatments). Histological analysis of RCAS-PDGF glioblastoma tissue shows that ST-401 triggers mitotic arrest of glioblastoma cells. ST-401 represents a promising lead compound for the treatments for patients diagnosed with glioblastomas.

100 项与 DermaXon LLC 相关的药物交易

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100 项与 DermaXon LLC 相关的转化医学

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管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

药物发现

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5

临床前

其他

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当前项目

药物(靶点)	适应症	全球最高研发状态

DX-416 ( T-type calcium channel )	疼痛更多	临床前
DX-0308 ( CYP26A1 x CYP26B1 )	鱼鳞病更多	临床前
DX-643	自身炎症性疾病更多	临床前
DX-465	角化病更多	临床前
DX-814	自身炎症性疾病更多	临床前