Abstract: The invention provides well-defined and stable pharmaceutical compositions comprising indole derivatives of general formula 1, a process for the preparation of di-hydrochloride salts comprising a high content of the pharmacologically active isomer suitable for industrial production, and use of these in pharmaceutical compositions. The invention further provides a method for use of said compounds for the treatment of cancer. The invention also provides methods to use these compounds in conjunction with other therapies commonly used for treating cancer diseases.

Abstract: A cell permeable iron chelator, optionally in combination with an autophagy inhibiting agent, is used for treating a solid cancer tumor in a person. A preferred chelator is an alkyl substituted N-(1-pyridine-2-yl-methylidene)-N-(9H-1,3,4,9-tetraaza-fluoren-2-yl)-hydrazine. A preferred autophagy inhibiting agent is chloroquine. Also disclosed is a pharmaceutical composition comprising iron chelator, pharmaceutically acceptable carrier and, optionally, autophagy inhibiting agent; and a method of treating cancer by administering cancer combating-effective amount(s) of the iron chelator or the combination of iron chelator and autophagy inhibiting agent.

Abstract: A method for screening a compound to determine whether the compound is a proteasome deubiquitinating inhibitor of high specificity comprises contacting the compound with human 19S regulatory particles (19S RP) of 26S proteasome and determining whether the compound inhibits activity of deubiquitinating (DUB) enzymes UCHL5 and USP14; inhibition of UCHL5 and USCP14 activities indicates that the compound is a proteasome deubiquitinating inhibitor of high specificity.

Abstract: In a cytotoxic compound of the general formula (I) R is H or methyl or methylene substituted by C1-C4 straight or branched alkyl, R1 is selected from the group consisting of H, C1-C4 straight or branched alkyl, methoxy, methoxy substituted by from one to three fluorine, halogen; R2 is H or C1-C4 straight or branched alkyl; X is CH or N; Y is CH or N.

Abstract: Compounds of the general structure S-1, wherein X and R1-R5 are defined in the specification, are capable of abrogating the deubiquitinating (DUB) activity of the 19S RP DUBs and are useful in methods and compositions for treating cancer, in particular, cancer tumors refractory to treatment by state-of-the-art chemotherapy.

Abstract: A method for screening a compound to determine whether the compound is a proteasome deubiquinating inhibitor of high specificity comprises contacting the compound with human 19S regulatory particles (19S RP) of 26S proteasome and determining whether the compound inhibits activity of deubiquinating (DUB) enzymes UCHL5 and USP14; inhibition of UCHL5 and USCP14 activities indicates that the compound is a proteasome deubiquinating inhibitor of high specificity.

Abstract: Compounds of the general structure S-1, wherein X and R1-R5 are defined in the specification, are capable of abrogating the deubiquitinating (DUB) activity of the 19S RP DUBs and are useful in methods and compositions for treating cancer, in particular, cancer tumors refractory to treatment by state-of-the-art chemotherapy.

Abstract: A cell permeable iron chelator, optionally in combination with an autophagy inhibiting agent, is used for treating a solid cancer tumour in a person. A preferred chelator is an alkyl substituted N-(1-pyridine-2-yl-methylidene)-N-(9H-1,3,4,9-tetraaza-fluoren-2-yl)-hydrazine. A preferred autophagy inhibiting agent is chloroquine. Also disclosed is a pharmaceutical composition comprising iron chelator, pharmaceutically acceptable carrier and, optionally, autophagy inhibiting agent; and a method of treating cancer by administering cancer combating-effective amount(s) of the iron chelator or the combination of iron chelator and autophagy inhibiting agent.

Abstract: A method of treating in a person a cancer tumor refractory to treatment with bortezomib or an agent sharing the apoptosis generating activity of bortezomib or any other anti-cancer drug, comprises administering to the person, in a pharmaceutically acceptable carrier, a pharmacologically effective dose of an agent selected from the group consisting of b-AP15 and other proteasome inhibitor abrogating the deubiquitinating (DUB) activity of the 19S RP DUBs.