The present disclosure describes the synthesis of peptidomimetic macrocycles and methods of using peptidomimetic macrocycles to treat a condition. The present disclosure also describes methods of using peptidomimetic macrocycles in combination with at least one additional pharmaceutically-active agent for the treatment of a condition, for example, cancer.

The present disclosure describes the synthesis of peptidomimetic macrocycles and methods of using peptidomimetic macrocycles to treat a condition. The present disclosure also describes methods of using peptidomimetic macrocycles in combination with at least one additional pharmaceutically-active agent for the treatment of a condition, for example, cancer.

The present disclosure describes the synthesis of peptidomimetic macrocycles and methods of using peptidomimetic macrocycles to treat a condition. The present disclosure also describes methods of using peptidomimetic macrocycles in combination with at least one additional pharmaceutically-active agent for the treatment of a condition, for example, cancer.

The present disclosure relates to compositions comprising a solubilizing agent and a peptide compound and/or a conjugate compound, processes, methods and uses thereof for treatment of cancer or aggressive cancer. For example, the conjugate compounds can comprise the formula of A-(B)n, wherein A is a peptide compound; and B is at least one therapeutic agent, and the peptide compounds can comprise compounds of formula X.sub.1X.sub.2X.sub.3X.sub.4X.sub.5GVX.sub.6AKAGVX.sub.7NX.sub.8FKSESY (I) (SEQ ID NO: 1) (X.sub.9).sub.nGVX.sub.10AKAGVX.sub.11NX.sub.12FKSESY (II) (SEQ ID NO: 2) YKX.sub.13LRRX.sub.14APRWDX.sub.15PLRDPALRX.sub.16X.sub.17L (III) (SEQ ID NO: 3) YKX.sub.18LRR(X.sub.19).sub.nPLRDPALRX.sub.20X.sub.21L (IV) (SEQ ID NO: 4) IKLSGGVQAKAGVINMDKSESM (V) (SEQ ID NO: 5) IKLSGGVQAKAGVINMFKSESY (VI) (SEQ ID NO: 6) IKLSGGVQAKAGVINMFKSESYK (VII) (SEQ ID NO: 7) GVQAKAGVINMFKSES Y (VIII) (SEQ ID NO: 8) GVRAKAGVRNMFKSESY (IX) (SEQ ID NO: 9) GVRAKAGVRN(Nle)FKSESY (X) (SEQ ID NO: 10) YKSLRRKAPRWDAPLRDPALRQLL (XI) (SEQ ID NO: 11) YKSLRRKAPRWDAYLRDPALRQLL (XII) (SEQ ID NO: 12) YKSLRRKAPRWDAYLRDPALRPLL (XIII) (SEQ ID NO: 13) wherein X.sub.1 to X.sub.21 and n can have various different values and wherein at least one protecting group and/or at least one labelling agent is optionally connected to said peptide compound at an N- and/or C-terminal end.

The present disclosure relates to compositions comprising a solubilizing agent and a peptide compound and/or a conjugate compound, processes, methods and uses thereof for treatment of cancer or aggressive cancer. For example, the conjugate compounds can comprise the formula of A-(B)n, wherein A is a peptide compound; and B is at least one therapeutic agent, and the peptide compounds can comprise compounds of formula X.sub.1X.sub.2X.sub.3X.sub.4X.sub.5GVX.sub.6AKAGVX.sub.7NX.sub.8FKSESY (I) (SEQ ID NO: 1) (X.sub.9).sub.nGVX.sub.10AKAGVX.sub.11NX.sub.12FKSESY (II) (SEQ ID NO: 2) YKX.sub.13LRRX.sub.14APRWDX.sub.15PLRDPALRX.sub.16X.sub.17L (III) (SEQ ID NO: 3) YKX.sub.18LRR(X.sub.19).sub.nPLRDPALRX.sub.20X.sub.21L (IV) (SEQ ID NO: 4) IKLSGGVQAKAGVINMDKSESM (V) (SEQ ID NO: 5) IKLSGGVQAKAGVINMFKSESY (VI) (SEQ ID NO: 6) IKLSGGVQAKAGVINMFKSESYK (VII) (SEQ ID NO: 7) GVQAKAGVINMFKSES Y (VIII) (SEQ ID NO: 8) GVRAKAGVRNMFKSESY (IX) (SEQ ID NO: 9) GVRAKAGVRN(Nle)FKSESY (X) (SEQ ID NO: 10) YKSLRRKAPRWDAPLRDPALRQLL (XI) (SEQ ID NO: 11) YKSLRRKAPRWDAYLRDPALRQLL (XII) (SEQ ID NO: 12) YKSLRRKAPRWDAYLRDPALRPLL (XIII) (SEQ ID NO: 13) wherein X.sub.1 to X.sub.21 and n can have various different values and wherein at least one protecting group and/or at least one labelling agent is optionally connected to said peptide compound at an N- and/or C-terminal end.

The present invention is directed to a method of treatment, including prevention or reducing the likelihood of adverse effects of chemotherapy comprising reducing and/or inhibiting chemotherapy-induced adverse effects (CIAE), especially central nervous system adverse effects, such as cognitive effects (especially chemotherapy induced cognitive impairment or CICI, also referred to as reduced cognition, cognitive impairment or chemobrain) by administering to the patient in need, including co-administering to the subject in need a pharmaceutically effective amount of a protein kinase C (PKC, often, PKC α and/or β) inhibitor, alone or in combination with a lithium salt. Related pharmaceutical compositions are also provided by the present invention.

The present invention is directed to a method of treatment, including prevention or reducing the likelihood of adverse effects of chemotherapy comprising reducing and/or inhibiting chemotherapy-induced adverse effects (CIAE), especially central nervous system adverse effects, such as cognitive effects (especially chemotherapy induced cognitive impairment or CICI, also referred to as reduced cognition, cognitive impairment or chemobrain) by administering to the patient in need, including co-administering to the subject in need a pharmaceutically effective amount of a protein kinase C (PKC, often, PKC α and/or β) inhibitor, alone or in combination with a lithium salt. Related pharmaceutical compositions are also provided by the present invention.

The present invention is directed to a method of treatment, including prevention or reducing the likelihood of adverse effects of chemotherapy comprising reducing and/or inhibiting chemotherapy-induced adverse effects (CIAE), especially central nervous system adverse effects, such as cognitive effects (especially chemotherapy induced cognitive impairment or CICI, also referred to as reduced cognition, cognitive impairment or chemobrain) by administering to the patient in need, including co-administering to the subject in need a pharmaceutically effective amount of a protein kinase C (PKC, often, PKC α and/or β) inhibitor, alone or in combination with a lithium salt. Related pharmaceutical compositions are also provided by the present invention.

The present disclosure provides, inter alia, methods for treating diseases, e.g., a cancer, in a subject by targeting oncogenic lipids in cells, including increasing lipid-based reactive oxygen species (ROS) by inhibiting coenzyme Q.sub.10 (CoQ.sub.10) production. Methods for treating a subject with a cancer that is sensitive to an oncolipid-targeting therapy, e.g., ADCK3 inhibition, are also provided. Further provided are methods for modulating coenzyme Q.sub.10 (CoQ.sub.10) level in a subject, including determining CoQ.sub.10 levels by LC-MS.

The present disclosure provides, inter alia, methods for treating diseases, e.g., a cancer, in a subject by targeting oncogenic lipids in cells, including increasing lipid-based reactive oxygen species (ROS) by inhibiting coenzyme Q.sub.10 (CoQ.sub.10) production. Methods for treating a subject with a cancer that is sensitive to an oncolipid-targeting therapy, e.g., ADCK3 inhibition, are also provided. Further provided are methods for modulating coenzyme Q.sub.10 (CoQ.sub.10) level in a subject, including determining CoQ.sub.10 levels by LC-MS.