Identification of the Antisickling Compounds in SCD-101

SCD-101 中抗镰化化合物的鉴定

基本信息

批准号：
9407759
负责人：
Robert Swift
金额：
$ 22.47万
依托单位：
INVENUX, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-17 至 2020-01-16
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9407759
关键词：
Acute Adult Adverse effects Affect Age American Antineoplastic Agents Antisickling Agents Biological Assay Birth Blood Botanicals Cells Cessation of life Child Clinical Research Colorado Deoxygenated Sickle Hemoglobin Developing Countries Development Disease Disease Progression Dose Drug Kinetics Erythrocytes Event Fatigue Fractionation Genes Goals Grant Hemoglobin Hereditary Disease Hospitalization Human In Vitro Libraries Liquid Chromatography Mass Fragmentography Measures Medical Molecular Mus Mutation Neurocognitive Opiates Organ Organ failure Pain Participant Pathogenesis Patients Pediatric Hospitals Pharmaceutical Preparations Pharmacodynamics Pharmacology Pharmacotherapy Phase Philadelphia Placebos Plasma Polymers Property Proteomics Quality of life Renal function Research Sickle Cell Sickle Cell Anemia Signs and Symptoms Sorghum Sorghum vulgare Spleen Stroke Structure Symptoms Testing Transgenic Mice Transgenic Organisms United States United States Food and Drug Administration Universities Variant Visit Work beta Globin chemical fingerprinting chronic pain clinical development common symptom cost drug development follow-up hydroxyurea in vivo metabolomics mortality mouse model multiorgan damage polymerization sickling trait treatment duration

项目摘要

ABSTRACT Sickle cell disease (SCD) affects approximately 100,000 people in the United States and millions worldwide. Symptoms appear shortly after birth, and in less developed countries the majority of children with SCD die before the age of five. In the U.S., SCD patients suffer chronic pain and fatigue, severe acute painful crises requiring hospitalization and opiates, strokes, and multi-organ damage, and have an average mortality in their 40s. The only FDA approved drug for adults with SCD is the anticancer drug hydroxyurea. New treatments are desperately needed for both children and adults with SCD. SCD-101 is a botanical drug that inhibits red blood cell sickling in vitro and in vivo. The formation of sickle shaped red blood cells, caused by the polymerization of deoxygenated sickle hemoglobin, is the primary and causative event in the molecular pathogenesis of sickle cell disease; therefore, inhibition of sickling by SCD-101 should ameliorate the signs, symptoms, and slow the progression of sickle cell disease. In a Phase 1B study, SCD-101 was shown to be safe and reduced pain and fatigue, the two most common symptoms of sickle cell disease. The compounds in SCD-101 responsible for the antisickling activity are unknown, as is the mechanism of antisickling. Identification of the antisickling compounds would assist in clinical development and may enable the development of a more potent and effective drug for the treatment of sickle cell disease. Identification of the antisickling compounds would assist in the elucidation of the mechanism by which SCD-101 inhibits red blood cell sickling and point the way to a new target for antisickling drugs, and the development of a new class of compounds to treat sickle cell disease.

抽象的镰状细胞疾病（SCD）在美国影响约100,000人和数百万全世界。出生后不久出现症状，在不太发达国家，大多数儿童 SCD死于五岁之前。在美国，SCD患者遭受慢性疼痛和疲劳，严重急性疼痛危机需要住院和鸦片，中风和多器官损害，并具有 40多岁的平均死亡率。 SCD成人唯一获得FDA批准的药物是抗癌药物羟基脲。 SCD的儿童和成人都迫切需要新的治疗方法。 SCD-101是一种植物药，可在体外和体内抑制红细胞疾病。这镰状血细胞的形成，由镰状镰刀的聚合引起血红蛋白是镰状细胞疾病分子发病机理中的主要和致病事件。因此，SCD-101对疾病的抑制作用应改善体征，症状，并减慢镰状细胞疾病的进展。在一项1B期研究中，SCD-101被证明是安全的疼痛和疲劳，这是镰状细胞疾病的两个最常见症状。 SCD-101中负责抗分活性活性的化合物尚不清楚，反智能机制。鉴定抗质化合物将有助于临床开发并可能使开发更有效，更有效的药物来治疗镰状细胞性贫血症。鉴定抗质化合物将有助于阐明 SCD-101抑制红细胞病的机制，并将其指向新目标的道路抗药性药物，以及开发新的化合物来治疗镰状细胞疾病。