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公开(公告)号：US20240390455A1
公开(公告)日：2024-11-28
申请号：US18797990
申请日：2024-08-08
Inventor： Olga Rafikova , Ruslan Rafikov
Abstract: Inositol monophosphatase 1 (IMPA1) controls the activity of the primary cell proliferation signaling cascades activated through the inositol-dependent phosphorylation of Akt and PKCs. Furthermore, IMPA1-mediated control of cell proliferation involves the recruitment of cytosolic IMPA1 on a plasma membrane by the receptor for advanced glycation endproducts (RAGE). Interaction between IMPA1 and RAGE redistributes inositols from the cytosolic pool to membrane microdomains and amplifies the synthesis of membrane-bound phosphatidylinositols (PtdIns) to trigger inositol-dependent cell proliferation. Thus, the peptide compositions described herein inhibit the formation of the complex between IMPA1 and RAGE (e.g., a pathogenic complex) to control over-proliferative cells.
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2.发明申请公开(公告)号：US20230073725A1
公开(公告)日：2023-03-09
申请号：US17792902
申请日：2021-01-14
Inventor： Ruslan Rafikov , Olga Rafikova
Abstract: The present invention features a method comprising a metabolomic biomarker panel representing a metabolomic profile/fingerprint and methods of applying the profile to diagnose, monitor, and guide treatment for PAH. The profile comprises a unique panel of 36 metabolomic biomarkers/metabolites detected in plasma and/or urine obtained from the patient. The present invention allows for identification of patients with PAH in early-stage disease, before the condition has progressed sufficiently to produce clinical symptoms, and uniquely distinguishes PAH from pulmonary hypertension due to type 2 Diabetes Mellitus (DM) and/or left heart disease. The present invention allows for pre-screening of patients to identify PAH at the asymptomatic stage or help to minimize the time for PAH diagnosis after initial symptom onset.
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公开(公告)号：US20250101204A1
公开(公告)日：2025-03-27
申请号：US18725609
申请日：2023-02-28
Inventor： Ruslan Rafikov , Olga Rafikova
Abstract: High mobility group box protein 1 (HMGB1) is a nuclear protein released during cell damage and stimulates inflammatory and proliferative pathways in the surviving neighboring cells. HMGB1 contains three cysteine residues (e.g., 23/45/106) involved in the extracellular HMGB1 oligomerization and receptor binding. The peptide compositions described herein shield the aforementioned cysteine residues, which block HMGB1 from binding to DNA and, thus, reduce apoptotic signaling within a cell. Furthermore, methods of treating inflammatory disease (e.g., PAH) by administering said peptide composition are described herein.
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公开(公告)号：US20230073946A1
公开(公告)日：2023-03-09
申请号：US17794229
申请日：2021-01-20
Inventor： Ruslan Rafikov , Olga Rafikova
Abstract: The present invention is a targeted peptide conjugated with an antioxidant, NO, to inhibit Akt nitration. The nitroxide peptide (NP), comprises two parts, one being the peptide part with the affinity to Akt near Tyr 350 residue (Ser-Arg-IIe-Arg-Ser; SRIRS)—and the other, a conjugated antioxidant—nitroxide (3-Carboxy-2,2,5,5-tetramethyl-3-pyrroline-1-yloxy) covalently attached to the free N-terminal amine. It can be utilized for treating pulmonary arterial hypertension (PAH) with potential application in other abnormal proliferative disorders such as cancer. The present invention features targeted selectivity for Akt nitration and does not affect Akt phosphorylation nor other physiological processes controlled by Akt signaling pathways. The present invention may also apply to other proliferative disorders including cancer or other disorders that cause or are caused by Akt nitration or protein oxidation.
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