Unique Compound Inhibits Angiogenesis in Cancer and Eye Diseases
Advantages of ScA include: A bioactive lipopeptide that can directly integrate into lipophilic structures such as liposomes, thus acting a bioactive structural component. This does not require active uptake into the liposome interior, and leaves the interior free for other cargo. Excellent potency, with an IC50 of 0.5pM against human endothelial cells and 80nM in zebra fish;Long, lipophilic hydrocarbon chains are readily formulated into liposomes, which can be further customized and or targeted.; and Combination therapy whereby ScA melts into the liposomal bilayer and additional anti-cancer drug(s) can be loaded into the liposomal lumen.In sum, ScA's unique, lipophilic structure confers improved functionality and efficacy, which may greatly improve the therapeutic window over other, anti-angiogenic drugs.
The promise of anti-angiogenic drugs in is reflected in the plethora of clinical trials. The obvious applications are reflected in the distribution of ~3000 human anti-angiogenesis trials: ~85% are designed to treat various forms of cancer and ~10% are for macular degeneration and a other eye diseases (e.g., choroid & retinal diseases)
University researchers have synthesized a novel lipopeptide, Somocystinamide A (ScA), which is a synthetic version of a compound isolated from marine cyanobacteria. ScA is distinguished by a lipophilic structure similar to native membrane components and this unique structure enables ScA to directly integrate into cellular membranes, perturb normal lipid homeostasis and selectively activate caspase 8, leading to programmed cell death.
Patent Number: US20100266675A1
Application Number: US2009600930A
Inventor: Gerwick, William | Wrasidlo, Wolfgang | Carson, Dennis | Stupack, Dwayne | Suyama, Takashi
Priority Date: 21 May 2007
Priority Number: US20100266675A1
Application Date: 8 Jul 2010
Publication Date: 21 Oct 2010
IPC Current: A61K0009127 | A61K003800 | A61P003500 | C07K000200
US Class: 424450 | 435375 | 5140011 | 5140193 | 530300
Assignee Applicant: The Regents of the University of California
Title: LIPOPROTEINS, LIPOPEPTIDES AND ANALOGS, AND METHODS FOR MAKING AND USING THEM
Usefulness: LIPOPROTEINS, LIPOPEPTIDES AND ANALOGS, AND METHODS FOR MAKING AND USING THEM
Summary: In the manufacture of a medicament, pharmaceutical composition for the treatment, prevent or amelioration of diseases or conditions associated with dysfunctional angiogenesis and/or abnormally proliferating blood vessels comprising endothelial or capillary cells, neovasculature related to (within, or providing a blood supply to) a tumor, for treating psoriasis, endometriosis, diabetic retinopathy, wet-age related macular degeneration or abnormal uterine bleeding, rheumatoid arthritis, choroidal neovascularization, pyogenic granuloma, pulmonary edema, female reproductive cycling disorders, pulmonary tuberculosis, benign prostate hyperplasia, autoimmune disease, infectious disease, neovascular glaucoma, arterio-venous (AV) malformation formation, pulmonary AV malformation, Osler-Weber syndrome, myocardial angiogenesis, plaque neovascularization, telangiectasia, hemophiliac joints, angio-fibroma, wound granulation, wound healing, telangiectasia psoriasis scleroderma, pyogenic granuloma, coronary collaterals, ischemic limb angiogenesis, rubeosis, arthritis, diabetic neovascularization, fractures, vasculo genesis, lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), primary CNS lymphoma, spinal axis tumors, brain stem glioma or pituitary adenoma, for inducing apoptosis in a cell, and for killing cancer cell, endothelial or neovascular cell (claimed).
Novelty: New lipoproteins/lipopeptides useful in a medicament for treating e.g. diabetic retinopathy, rheumatoid arthritis, choroidal neovascularization, pyogenic granuloma, endometriosis, pulmonary edema, pulmonary tuberculosis
Disease Diagnostic/Treatment
Cancer/Tumor
9045401
State Of Development ScA has been incorporated into stable, liposomal nanoparticles of 100 nM in size, which retain full potency and excellent activity in vitro and in vivo. In vivo, ScA blocks endothelial cell tube formation and developmental angiogenesis in zebrafish models. ScA: Intellectual Property Info Patent pending; publication number: US20100266675 Related Materials Suyama, T.L. and W.H. Gerwick, Stereospecific total synthesis of somocystinamide A. Org Lett, 2008. 10(20): p. 4449-52. Additional Technologies by these Inventors Tech ID/UC Case 22493/2007-225-0 Related Cases 2007-225-0
Wrasidlo, W., et al., The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8. Proc Natl Acad Sci U S A, 2008. 105(7): p. 2313-8.
Nogle, L.M. and W.H. Gerwick, Somocystinamide A, a novel cytotoxic disulfide dimer from a Fijian marine cyanobacterial mixed assemblage. Org Lett, 2002. 4(7): p. 1095-8.
www.marinebiotech.org
Discovery of Natural Antiangiogenic Leads
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