PALOMA PHARMA 529 TREATMENT FOR SIV STUDY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Palomid 529(P529)是一种人工合成的小分子药物，它抑制参与信号调节翻译的细胞途径。当这一途径被异常激活时，它可能导致包括癌症、眼病和皮肤病在内的各种病理情况，并可能促进病毒复制。P529抑制这一途径的异常激活，并在癌症和眼部疾病的动物模型中显示出活性。在SIV感染的细胞培养上进行P529的体外检测。用25um或250uM棕榈酸处理的细胞培养物显示出抗病毒活性。较低剂量均为阴性。 基于良好的体外实验结果，两只感染SIVmac251的印度猕猴被给予P529 12 mg/kg连续5天的治疗。然后，这些动物被允许在没有接受治疗的情况下休息9天。休息期结束后，给予P529 24 mg/kg，连续5天。采集血样以监测血浆病毒载量水平、体内药物浓度和基本血液参数是否有任何毒性。在两种剂量下均未观察到血浆病毒载量的下降。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Palomid 529 (P529), is a synthetic small molecule drug that inhibits a cellular pathway involved in signaling to regulate translation. When this pathway is aberrantly activated, it can lead to a variety of pathological conditions including cancer, ocular and skin diseases and can promote viral replication. P529 inhibits the aberrant activation of this pathway and has shown activity when tested in animal models of cancer and ocular diseases. P529 was tested in vitro in SIV infected cell cultures. Cell cultures pre-treated with 25uM or 250uM Palomid showed anti-viral activity. Lower dose were negative. Based on promising in vitro results, two SIVmac251 infected, Indianorigin rhesus macaques were treated with 12 mg/kg P529 for five consecutive days. The animals were then allowed to rest, untreated, for nine days. After this rest period, the animals were treated with 24 mg/kg P529 for five consecutive days. Blood samples were collected to monitor plasma virus load levels, in vivo drug concentrations and basic blood parameters for any toxicity. No decreases in plasma virus load were observed at either dose.