Mainline Biosciences LLC

Cohbar, Inc.

Eli Lilly and Company

Mainline Biosciences (Shanghai) Co., Ltd.

Liang Zeng Yan

Junge Zhang

Wendy Luo

Kent K Grindstaff

Kenneth C Cundy

Remi Magnan

Yongjin Yao

Sheng-Bin Peng

Wayne David Kohn

The present invention provides a selective CXCR4 binding peptide conjugate (“PC”), and a method for using and producing the same. In particular, the selective CXCR4 binding peptide conjugate of the invention comprises a peptide portion that selectively binds to CXCR4 and a medically useful compound, such as an imaging agent, a diagnostic agent, or a therapeutically or pharmaceutically active compound. In one particular embodiment, the selective CXCR4 binding peptide conjugate (“PC”) is of the formula: or a pharmaceutically acceptable salt thereof, wherein a, b, AA, AA, Ar, X, and AAare those defined herein. The peptide conjugate of the invention can be used in a variety of medical applications including, but not limited to, a targeted drug delivery or imaging a patient or diagnosing a patient for a disease or a clinical condition associated with overexpression and/or upregulation of CXCR4, such as cancers, HIV infection, and immune disorders. Compositions, kits and methods are also disclosed herein for such uses.

Selective CXCR4 binding peptide conjugate and methods for making and using the same

The present invention provides a composition comprising a therapeutic agent and a C-X-C chemokine receptor type 4 (CXCR4) antagonist, and methods for using the same. Compositions and methods of the invention can be used to treat cancer, viral infection, immune disorders (e.g., rheumatoid arthritis), pulmonary fibrosis, or any other clinical condition associated with abnormal expression (e.g., overexpression and/or upregulation) of CXCR4. Compounds of the invention can also be used in stem cell therapeutics.

Composition comprising a therapeutic agent and a CXCR4 selective antagonist and methods for using the same

Provided herein are peptides and peptide analogs and methods of treating a metabolic disease, e.g., obesity, diabetes, methods of treating cancer, methods of treating a liver disease, and methods of modulating fatty acid metabolism.

Therapeutic peptides

The present invention provides a selective CXCR4 binding peptide conjugate ('PC'), and a method for using and producing the same. In particular, the selective CXCR4 binding peptide conjugate of the invention comprises a peptide portion that selectively binds to CXCR4 and a medically useful compound, such as an imaging agent, a diagnostic agent, or a therapeutically or pharmaceutically active compound. In one particular embodiment, the selective CXCR4 binding peptide conjugate ('PC') is of the formula: or a pharmaceutically acceptable salt thereof, wherein a, b, AA, AA, Ar, X, and AAare those defined herein. The peptide conjugate of the invention can be used in a variety of medical applications including, but not limited to, a targeted drug delivery or imaging a patient or diagnosing a patient for a disease or a clinical condition associated with overexpression and/or upregulation of CXCR4, such as cancers, HIV infection, and immune disorders. Compositions, kits and methods are also disclosed herein for such uses.

The present invention provides method treating a subject suffering from a clinical condition associated with CXCR4 activity, said method comprising administering to a subject in need of such a treatment a therapeutically effective amount of a compound of the formula: or a pharmaceutically acceptable salt thereof, wherein a is 0 or 1; AAalong with the sulfur atom that is attached thereto is 3-mercaptopropionic acid, optionally substituted cysteine, or optionally substituted homocysteine; AAalong with the sulfur atom that is attached thereto is cysteine or homocysteine; Aris an optionally substituted aryl; Xis Arg, Dap, Dab, Orn, Lys, Dap(iPr), Dab(iPr), Orn(iPr), or Lys(iPr); Xis Arg, Dap, Dab, Orn, Lys, Dap(iPr), Dab(iPr), Orn(iPr), Lys(iPr), a D-isomer thereof, or absent; Xis Gly or absent; Xis Phe, 2Nal, 1Nal, or absent; Xis Gly or absent; Ris &#x2014;ORor &#x2014;NHR; Ris H or alkyl; and Ris H, alkyl, optionally substituted aryl, optionally substituted aralkyl. Methods of the invention can be used to treat a variety of clinical conditions, including but not limited to, cancers, pulmonary fibrosis, HIV infection, rheumatoid arthritis, and other immune disorders.

CXCR4 antagonists and methods of use

The present invention provides a compound that can be used for targeted drug delivery, imaging a patient, or diagnosing a subject for a clinical condition which is believed to be associated with overexpression and/or upregulation of CXCR4. In particular, the present invention provides a high affinity CXCR4 selective binding ligand peptide conjugate (PC) of the Formula: P-(L-A)(I) or a pharmaceutically acceptable salt thereof, and a method for using and producing the same. The high affinity CXCR4 selective binding ligand peptide conjugate (PC) of the invention is useful in diagnosing, treating or imaging a patient. In compound of Formula (I), n is an integer from 1 to the sum of (the total number of amino acid resides in P and the total number of side-chain functional group in the amino acid residue of P); each A is independently a diagnostic agent, a therapeutic agent, or an imaging agent; L is a linker or absent; and P is a high affinity CXCR4 selective binding peptidyl ligand. In particular, the invention provides to a targeted drug delivery or imaging a patient or diagnosing a patient for a disease of which overexpression and/or upregulation of CXCR4 is implicated, such as cancers, HIV infection, and immune disorders. Compositions and kits peptide conjugate of Formula I as well as methods for using and producing peptide conjugate of Formula I are disclosed herein.

High affinity CXCR4 selective binding conjugate and method for using the same

The present invention provides compounds that are antagonists of CXCR4 and methods for using the same for treatment of a clinical condition associated with CXCR4 activation. In particular, compounds of the invention include cyclic peptides. Compounds of the invention can be used to treat a variety of clinical conditions, including but not limited to, cancers, pulmonary fibrosis, HIV infection, rheumatoid arthritis, and other immune disorders. In addition, compounds of the invention can also be used in stem cell therapy. In one particular embodiment, compounds of the invention are cyclic peptides of the formula: or a pharmaceutically acceptable salt thereof, wherein a is 0 or 1; AAalong with the sulfur atom that is attached thereto is 3-mercaptopropionic acid, optionally substituted cysteine, or optionally substituted homocysteine; AAalong with the sulfur atom that is attached thereto is cysteine or homocysteine; Aris an optionally substituted aryl; Xis Arg, Dap, Dab, Orn, Lys, Dap(iPr), Dab(iPr), Orn(iPr), or Lys(iPr); Xis Arg, Dap, Dab, Orn, Lys, Dap(iPr), Dab(iPr), Orn(iPr), Lys(iPr), a D-isomer thereof, or absent; Xis Gly or absent; Xis Phe, 2Nal, 1Nal, or absent; Xis Gly or absent; Ris &#x2014;ORor &#x2014;NHR; Ris H or alkyl; and Ris H, alkyl, optionally substituted aryl, optionally substituted aralkyl.

Provided are lactam-cyclized peptide CXCR4 antagonists useful in the treatment of cancers, rheumatoid arthritis, pulmonary fibrosis, and HIV infection.

Growing community of inventors

Carmel, IN, United States of America

Liang Zeng Yan