Topotarget UK Limited

James Ritchie

Ivars Kalvinsh

Einars Loza

Paul W Finn

Vija Gailite

Clare J Watkins

Igor Starchenkov

Klara Dikovska

Henri Lichenstein

Victor Andrianov

Daina Lolya

Maria Rosario Romero-Martin

James E S Duffy

C John Harris

Kathryn G Moore

Maxim Vorona

Kamille Dumong Erichsen

Jane Plumb

Nicholas Edwards

Maxwell Sehested

Rasma M Bokaldere

Irina Piskunova

Valentina Semenikhina

Xiaozhang Qian

Maria-Rosario Romero-Martin

Andris Amolins

Mike Jeffers

Kamille Dumong Petersen

James Es Duffy

Henri Lichtenstein

James E Duffy

The present invention pertains to a method for treating cancer, such as lung cancer, multiple myeloma, lymphoma, and epithelial ovarian cancer, comprising the administration to a patient in need thereof a first amount or dose of a histone deacetylase (HDAC) inhibitor, such as PXD-101, and a second amount or dose of another chemotherapeutic agent, such as dexamethasone or 5-fluorouracil, or an epidermal growth factor receptor (EGFR) inhibitor, such as Tarceva&#xda;, wherein the first and second amounts or doses together comprise a therapeutically effective amount.

Combination therapies using HDAC inhibitors

The present invention relates generally to methods for treating cancer. In one respect, the present invention relates to a method of treating a hematological cancer (e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof a therapeutically effective amount of a histone deacetylase inhibitor, for example, a histone deacetylase (HDAC) inhibitor as described herein, for example, PXD-101. In another respect, the present invention relates to a method of treating cancer (e.g., solid tumor cancer, e.g., rectal cancer, colon cancer, ovarian cancer, hematological cancer, e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof, a first amount of a histone deacetylase (HDAC) inhibitor, for example, a histone deacetylase inhibitor as described herein, for example, PXD-101, and a second amount of another chemotherapeutic agent, for example, another chemotherapeutic agent selected from: an antibody against VEGF, AVASTIN&#xae; (bevacizumab), an antibody against CD20, rituximab, bortezomib, thalidomide, dexamethasone, vincristine, doxorubicin, and melphalan, wherein the first and second amounts together comprise a therapeutically effective amount.

Histone deacetylase (HDAC) inhibitors for the treatment of cancer

The present invention relates generally to methods for treating cancer. In one respect, the present invention relates to a method of treating a hematological cancer (e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof a therapeutically effective amount of a histone deacetylase inhibitor, for example, a histone deacetylase (HDAC) inhibitor as described herein, for example, PXD-101. In another respect, the present invention relates to a method of treating cancer (e.g., solid tumour cancer, e.g., rectal cancer, colon cancer, ovarian cancer, hematological cancer, e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof, a first amount of a histone deacetylase (HDAC) inhibitor, for example, a histone deacetylase inhibitor as described herein, for example, PXD-101, and a second amount of another chemotherapeutic agent, for example, another chemotherapeutic agent selected from: an antibody against VEGF, AVASTIN&#xae; (bevacizumab), an antibody against CD20, rituximab, bortezomib, thalidomide, dexamethasone, vincristine, doxorubicin, and melphalan, wherein the first and second amounts together comprise a therapeutically effective amount.

The present invention relates generally to methods for treating cancer. In one respect, the present invention relates to a method of treating a hematological cancer (e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof a therapeutically effective amount of a histone deacetylase inhibitor, for example, a histone deacetylase (HDAC) inhibitor as described herein, for example, PXD-101. In another respect, the present invention relates to a method of treating cancer (e.g., solid tumor cancer, e.g., rectal cancer, colon cancer, ovarian cancer; hematological cancer, e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof, a first amount of a histone deacetylase (HDAC) inhibitor, for example, a histone deacetylase inhibitor as described herein, for example, PXD-101, and a second amount of an other chemotherapeutic agent, for example, an other chemotherapeutic agent selected from: an antibody against VEGF, AVASTIN&#xae; (bevacizumab), an antibody against CD20, rituximab, bortezomib, thalidomide, dexamethasone, vincristine, doxorubicin, and melphalan, wherein the first and second amounts together comprise a therapeutically effective amount.

Histone deacetylase (HDAC) inhibitors (PXD101) for the treatment of cancer alone or in combination with chemotherapeutic agent

This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

Carbamic acid compounds comprising a piperazine linkage as HDAC inhibitors

This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the formula (1) wherein: A is an aryl group; Qis an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: &#x2014;NRC(&#x2550;O)&#x2014; and &#x2014;C(&#x2550;O)NR&#x2014;; Ris an amido substituent; and, Qis an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psorias.

Carbamic acid compounds comprising an amide linkage as HDAC inhibitors

This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: wherein: Cy is independently a cyclyl group; Qis independently a covalent bond or cyclyl leader group; the piperazin-1,4-diyl group is optionally substituted; Jis independently a covalent bond or &#x2014;C(&#x2550;; O)&#x2014;; Jis independently &#x2014;C(&#x2550;O)&#x2014; or &#x2014;S(&#x2550;O)&#x2014;; Qis independently an acid leader group; wherein: Cy is independently: Ccarbocyclyl, Cheterocyclyl, or Caryl; and is optionally substituted; Qis independently: a covalent bond; Calkylene; or Calkylene-X&#x2014;Calkylene, &#x2014;X&#x2014;Calkylene, or Calkylene-X&#x2014;, wherein X is &#x2014;O&#x2014; or &#x2014;S&#x2014;; and is optionally substituted; Qis independently: Calkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or: Qis independently: Carylene; Carylene-Calkylene; Calkylene-Carylene; or, Calkylene-Carylene-Calkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: &#x2014;NR1C(&#x2550;O)&#x2014; and &#x2014;C(&#x2550;O)NR1-; R1 is an amido substituent; and, Q2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Qis a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: &#x2014;S(&#x2550;O)NR&#x2014; and &#x2014;NRS(&#x2550;O)&#x2014;; Ris a sulfonamido substituent; and, Qis an acid leader group; with the proviso that if J is &#x2014;S(&#x2550;O)NR&#x2014;, then Qis an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

Carbamic acid compounds comprising a sulfonamide linkage as HDAC inhibitors

This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Qis a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: &#x2014;S(&#x2550;O)NR&#x2014; and &#x2014;NRS(&#x2550;O)&#x2014;; R1 is a sulfonamido substituent; and, Qis an acid leader group; with the proviso that if J is &#x2014;S(&#x2550;O)NR&#x2014;, then Qis an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

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Abingdon, United Kingdom

James Ritchie