US 12,121,510 B2 · Compounds and methods to sensitize cancer cells to cisplatin

Abstract

The present invention generally relates to sensitizer compounds and their use to sensitize cancer and/or pre-cancerous cells of certain cancers to treatment with certain resistance-prone therapeutics used in cancer therapy. In embodiments, the conjugates of particular esters or amides of Near Infrared Dyes, are used as sensitizers to avoid or overcome therapeutic resistance once formed. In embodiments, the sensitizers include conjugates with Cisplatin, Simvastatin, Artemisinin, platin-based compounds or statins. In embodiments, the resistance prone cancer therapeutics include cisplatin, gemcitabine, doxorubicin, paclitaxel, docetaxel, and platin-based compounds. These may be administered in combination with the sensitizer, or the sensitizer itself may comprise an therapeutic-derived moiety conjugated to the sensitizer, for example as is the case for dye-CIS conjugated sensitizers. Alternatively, the sensitizer may be co-administered with one or more therapeutic. Embodiments of the invention may advantageously be used in cancers that have a tendency to develop resistance to such cancer therapeutics and/or to form metastases, including e.g. lung, pancreatic, prostate, testicular, ovarian, cervical, bladder, breast, head and neck, esophageal, and stomach, cancers, germ cell tumors, lymphomas and other cancers.

Claims19

Dependent claims

A sensitizer compound which is a DZ-DRG amide or ester conjugate, wherein a DZ-residue of formula FI or FII, via an amide or ester bond, is linked to the residue of a drug (DRG);

wherein the conjugated drug (DRG) is selected from the group consisting of Simvastatin (SIM), Artemisinin (ART), Doxorubicin (DOX), Paclitaxel (PAC), a statin, and a therapeutically functional derivative thereof, and wherein the DZ residue is selected from the group consisting of an amide DZ residue of formula I below
and an ester residue of formula II below
wherein ˜ represents a point of attachment to the conjugated drug (DRG).

A pharmaceutical composition comprising a sensitizer compound which is a DZ-DRG amide or ester conjugate and at least one pharmaceutically acceptable carrier;

wherein a DZ-residue of formula FI or FII, via an amide or ester bond, is linked to the residue of a DRG drug;
wherein the conjugated DRG of the sensitizer is selected from the group consisting of Simvastatin (SIM), Artemisinin (ART), a statin, and a therapeutically functional derivative thereof, and wherein the DZ residue is selected from the group consisting of an amide DZ residue of formula I below
and an ester DZ reside of formula II below
wherein ˜ represents a point of attachment to the conjugated drug (DRG).

1 more element

A method of sensitizing tumor, cancer, or precancerous cells present in a subject to the treatment with a RPT drug;

wherein the sensitizer is a DZ-DRG amide or ester conjugate comprising a conjugated DRG;
wherein the DRG is selected from the group consisting of Cisplatin (CIS), Simvastatin (SIM), Artemisin (ART), Doxorubicin (DOX), Paclitaxel (PAC), a platin-based compound, a statin, and a therapeutically functional derivative thereof;
wherein the RPT is selected from the group consisting of Cisplatin (CIS), Gemcitabine (GEM), Doxorubicin (DOX), Paclitaxel (PAC), Docetaxel (DT), a platin-based compound, and a therapeutically functional derivative thereof;
and wherein if the RPT is present in form of a DZ-conjugated RPT, and a platin-based compound or Cisplatin (CIS) is selected as DRG, then the selected platin-based or CIS DRG is not also selected as RPT in the DZ-conjugated RPT;
and wherein the DZ residue is selected from the group consisting of a DZ amide of formula FI, and a DZ ester of formula FII, shown below:
wherein ˜ represents a point of attachment to the conjugated drug (DRG);
and
the method comprising exposing a plurality of tumor, cancer or pre-cancerous cells to the RPT by administering a sensitizer compound to a subject in need of treatment with the RPT, in an amount and concentration sufficient to increase the sensitivity of the cells to the RPT.

5 more elements

Dependencies are inferred from the claim text.

Compounds and methods to sensitize cancer cells to cisplatin

Life of this patent

Compounds and methods to sensitize cancer cells to cisplatin

Life of this patent

Abstract

Claims19