A Phase 1 Study of AR-12 (2-Amino-N-[4-[5-(2 Phenanthrenyl)-3-(Trifluoromethyl)-1H-pyrazol-1-yl] Phenyl]-Acetamide) in Adult Patients With Advanced or Recurrent Solid Tumors or Lymphoma, for Which No Standard Therapy Is Available

The primary objective of this study in adults with advanced or recurrent solid tumors or lymphoma is to evaluate the safety and tolerability of AR-12 by describing dose-limiting toxicities (DLTs), and thereby establishing the maximum tolerated dose (MTD) or, in the absence of reaching an MTD, a recommended dose (RD) for additional study of oral AR-12 administered daily in cycles of 28 days (28 consecutive days of once daily treatment with at least a 7-day break between the first and second treatment cycles and recovery of toxicity to grade 1 or less, with no planned off-treatment days between subsequent cycles).

开始日期2009-08-01

申办/合作机构

Arno Therapeutics, Inc.

100 项与 AR-12 相关的临床结果

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100 项与 AR-12 相关的转化医学

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100 项与 AR-12 相关的专利（医药）

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105

项与 AR-12 相关的文献（医药）

2024-03-04·Cureus

Cryptococcosis and Cryptococcal Meningitis: A Narrative Review and the Up-to-Date Management Approach

Review

作者: Shrivastava, Shitij ; Ghazanfar, Haider ; Fortuzi, Ked ; Hasan, Khushbu Z ; Qureshi, Zaheer A ; Kandhi, Sameer ; Ghazanfar, Ali ; Dileep, Arundhati ; Altaf, Faryal

Cryptococcosis is a fungal infectious disease that enormously impacts human health worldwide. Cryptococcal meningitis is the most severe disease caused by the fungus Cryptococcus, and can lead to death, if left untreated. Many patients develop resistance and progress to death even after treatment. It requires a prolonged treatment course in people with AIDS. This narrative review provides an evidence-based summary of the current treatment modalities and future trial options, including newer ones, namely, 18B7, T-2307, VT-1598, AR12, manogepix, and miltefosine. This review also evaluated the management and empiric treatment of cryptococcus meningitis. The disease can easily evade diagnosis with subacute presentation. Despite the severity of the disease, treatment options for cryptococcosis remain limited, and more research is needed.

2023-10-25·Zhen ci yan jiu = Acupuncture research

电针通过抑制PDK1/Akt/HCN4通路改善大鼠神经源性尿潴留.

Article

作者: Zhang, Ren ; Li, Zheng-Fei ; Kuang, Yao ; Zhao, Guo-Rui

目的: 以3-磷酸肌醇依赖性蛋白激酶1（PDK1）/蛋白激酶B（Akt）/超极化激活环核苷酸门控离子通道4（HCN4）通路为切入点，探究电针治疗大鼠神经源性尿潴留的分子机制。方法: 实验选取SD雌性大鼠，采用改良Hassan Shaker脊髓全断法建立逼尿肌无力型尿潴留大鼠模型，并按随机数字表法随机分为模型组、电针组、PDK1抑制剂组、HCN4阻断剂组、电针+HCN4阻断剂组，每组20只，另取20只大鼠作为假手术组。电针组、电针+HCN4阻断剂组取大鼠“中极”“中髎”电针治疗20 min，1次/d，PDK1抑制剂组隔天1次腹腔注射OSU-03012（20 mg/kg），HCN4阻断剂组隔天1次腹腔注射伊伐布雷定（10 mg/kg），以上治疗均持续10 d。多通道生理记录仪检测大鼠尿流动力学指标；肌条实验检测逼尿肌兴奋性；HE染色观察膀胱形态学变化；免疫荧光双染法检测膀胱组织HCN4与酪氨酸蛋白激酶KIT（C-Kit）阳性表达；Western blot法检测膀胱组织PDK1/Akt/HCN4通路蛋白及热休克蛋白27（HSP27）表达。结果: 与假手术组相比，模型组大鼠出现排尿功能障碍，漏尿点压力、离体逼尿肌自发收缩频率、膀胱组织C-Kit荧光强度、HCN4⁺/C-Kit⁺共表达、HCN4及磷酸化（p）-HSP27/HSP27蛋白表达降低（P<0.05），膀胱最大容量及顺应性、离体逼尿肌收缩时最小张力、膀胱组织PDK1及p-Akt/Akt蛋白表达升高（P<0.05）；与模型组相比，电针组、PDK1抑制剂组大鼠以上指标均逆转（P<0.05）；与电针组相比，电针+HCN4阻断剂组和HCN4阻断剂组大鼠排尿功能障碍严重，漏尿点压力、自发收缩频率、C-Kit荧光强度、HCN4⁺/C-Kit⁺共表达、HCN4及p-HSP27/HSP27蛋白表达降低（P<0.05），膀胱最大容量及顺应性、离体逼尿肌收缩时最小张力、膀胱组织PDK1及p-Akt/Akt蛋白表达升高（P<0.05）。HE染色示模型组大鼠膀胱上皮组织脱落、层次紊乱，膀胱壁细胞空泡化、黏膜层及肌层中性粒细胞浸润等病理损伤明显，电针组及PDK1抑制剂组有所减轻，HCN4阻断剂组较模型组加重，电针+HCN4阻断剂组上述病理损伤较电针组严重。结论: 电针刺激“中髎”“中极”可能通过抑制PDK1/Akt通路活化，促进HCN4介导的逼尿肌兴奋性收缩、排尿电信号活化，从而改善神经源性尿潴留大鼠排尿功能障碍。.

2023-06-30·Bioinformation

Molecular docking analysis of MCL-1 inhibitors for breast cancer management

Article

作者: Asif Hussain, Akber ; Hanan Mamdouh, Alotaibi ; Marui, Ibrahim Shafei ; Abdulrahman, Alzahrani ; Mohammed Hadi, Ghawi ; Qamre, Alam ; Mohammad Azhar, Kamal ; Ali Abdullah, Asiri

Myeloid leukemia 1 (MCL-1), a BCL-2 protein family member, acts as an anti-apoptotic protein by interacting with pro-apoptotic BCL-2 proteins. Its overexpression is frequently observed in numerous cancer types including breast cancer, and is closely linked to the initiation and progression of tumors as well as poor prognosis and resistance to therapeutic interventions. Here, a database of 3402 chemicals with established therapeutic activity against various diseases was chosen and systematically screened against the MCL-1 protein. Visual inspection and binding energy analysis revealed that the compounds OSU-03012, Raltitrexed, Ostarine (MK-2866), Dovitinib (TKI-258), and Varespladib (LY315920) had strong binding affinity for the MCL-1 protein. Notably, their binding affinity was higher than that of the control compounds. These compounds exhibited strong interactions with critical amino acid residues of the MCL-1 protein. Furthermore, these compounds shared several common amino acid residue interactions with the control compounds. These findings suggest that these compounds may be useful as MCL-1 inhibitors in the treatment of breast cancer. However, additional experimental validation is required to confirm these findings.

100 项与 AR-12 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
淋巴瘤	临床1期	美国	Arno Therapeutics, Inc.	2009-08-01
淋巴瘤	临床1期	英国	Arno Therapeutics, Inc.	2009-08-01
复发性实体肿瘤	临床1期	美国	Arno Therapeutics, Inc.	2009-08-01
复发性实体肿瘤	临床1期	英国	Arno Therapeutics, Inc.	2009-08-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00978523 (ASCO2013)	临床1期	HR阳性/HER2低表达实体瘤	35	AR-12	(餘繭製範窪淵選鹹積蓋) = G2-1pt 膚蓋簾獵簾壓構夢鏇遞 (遞衊網餘窪夢選鬱鏇襯 ) 更多	-	2013-05-20