Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several new cytostatic drugs have entered clinical phase I-II studies for the treatment of leukemia: the most promising are pyrimidine analogs such as 5-aza-cytidine, 5-aza-2'-deoxycytidine, 5-aza-cytosine arabinoside, and 2',2'-difluorodeoxycytidine. Fludarabine, a fluorinated purine analog, appears to be active in CLL and multiple myeloma. Deoxycoformycin, an adenosine analog, showed good activity in the treatment of hairy cell leukemia and T-cell neoplasias. 2-chloro-deoxyadenosine has recently been introduced into the treatment of CLL and hairy-cell leukemia refractory to deoxycoformicin. Tiazofurin, an antimetabolite which interferes with nicotine-adenine-dinucleotide (NAD) metabolism, has been applied in CML blast crisis. Other agents include 13-cis retinoic acid and 1, 25-dihydroxy vitamin D3 as differentiation inducers, and homoharringtonine, an alkylating agent which is widely used for ANLL treatment in China. Among new anthracyclines, aclarubicin, idarubicin, THP-adriamycin and fluoro-adriamycin should be mentioned. Mitoxantrone, a substituted anthraquinone, has successfully been applied in the treatment of relapsed and refractory ANLL. Amsacrine (m-AMSA), finally, is a synthetic aminoacridine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in ANLL treatment. Studies using m-AMSA alone or in combination revealed comparable results to anthracycline--containing regimens. Cardiotoxicity of the anthracycline congestive type has not been observed with m-AMSA. The EORTC Leukemia Cooperative Group has successfully used m-AMSA in several trials prepositioning this drug stepwise: from relapsed and refractory ANLL, into intensive maintenance treatment during first remission in ANLL, and, still on-going, into intensive consolidation.
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PMID:New drugs in the treatment of acute and chronic leukemia with some emphasis on m-AMSA. 206 23

Inosine 5'-monophosphate dehydrogenase (IMPDH) represents an attractive target for the development of anticancer agents; however, there are no drugs aimed at this target for the treatment of cancer currently available on the market. Tiazofurin, a potent IMPDH inhibitor, reached clinical trials with Orphan Drug status for the treatment of patients in blast crisis of chronic myelogenous leukemia (CML); however, it was considered too toxic for application against other malignancies and no development has been reported for this drug since 2002. Formulations of mycophenolic acid, another potent inhibitor of IMPDH, are currently used for the prevention of rejection following transplantation, and against autoimmune diseases. More recently, numerous studies have demonstrated the potential of mycophenolic acid as an anticancer agent, with a phase I clinical trial in patients with advanced multiple myeloma ongoing. Furthermore, synergy between imantinib and mycophenolic acid in CML treatments has also been reported. Related compounds such as mycophenolic adenine dinucleotides, along with second-generation analogs, are undergoing preclinical evaluation, while another inhibitor of IMPDH, AVN-944, is currently in phase I clinical trials to investigate the treatment of hematological malignancies. This article reviews recent applications of IMPDH inhibitors as anticancer agents, and highlights the progress that has been made in this field.
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PMID:Recent development of IMP dehydrogenase inhibitors for the treatment of cancer. 1765 81