PALOMA PHARMA 529 TREATMENT FOR SIV STUDY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Palomid 529（P529）是一种合成的小分子药物，其抑制参与信号传导以调节翻译的细胞途径。 当该途径被异常激活时，它可导致多种病理状况，包括癌症、眼部和皮肤疾病，并可促进病毒复制。 P529抑制该途径的异常激活，并且在癌症和眼部疾病的动物模型中测试时显示出活性。在SIV感染的细胞培养物中体外测试P529。用25 uM或250 uM Palomid预处理的细胞培养物显示出抗病毒活性。 低剂量为阴性。 基于有希望的体外结果，两个SIVmac 251感染，印度用12 mg/kg P529连续5天处理原始恒河猴。 然后让动物休息9天，不给药。 在该休息期后，用24 mg/kg P529连续5天处理动物。 采集血液样本以监测血浆病毒载量水平、体内药物浓度和任何毒性的基本血液参数。 在任一剂量下均未观察到血浆病毒载量降低。

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.