Abstract: Compounds of the formula below are poly(ADP-ribosyl)transferase (PARP) inhibitors, and are useful as therapeutics in treatment of cancers and the amelioration of the effects of stroke, head trauma, and neurodegenerative disease. As cancer therapeutics, the compounds of the invention may be used, e.g., in combination with cytotoxic agents and/or radiation.

Abstract: The present invention relates to compounds capable of binding to the oncogene protein MDM2, processes for the preparation of such compounds, pharmaceutical preparations comprising such compounds, and uses of said compounds, e.g. in the therapeutic (including prophylactic) treatment of an animal or especially of the human body. The present further relates to methods of and compounds for inhibiting the growth of tumor cells which comprise the wild type p53 suppressor by interfering with the interaction between human p53 and human MDM2.

Abstract: The present invention relates to binding members that are capable of binding to and effecting the function of proteins useful in facilitating folding of large polypeptides. The present invention particularly relates to the chaperone CCT. The invention provides materials and methods for effecting the biological activity of CCT within the cell so as to prevent the folding to CCT substrates such as actin, tubulin or cyclin. The inventors provide specific binding members capable of occupying a CCT substrate binding site thereby preventing the substrate from binding. Further, the present invention provides methods for screening for such binding members which effect the biological activity of CCT.

Abstract: Compounds of the formula below are poly(ADP-ribosyl)transferase (PARP) inhibitors, and are useful as therapeutics in treatment of cancers and the amelioration of the effects of stroke, head trauma, and neurodegenerative disease. As cancer therapeutics, the compounds of the invention may be used, e.g., in combination with cytotoxic agents and/or radiation.

Abstract: This invention pertains to nitrogen mustard compounds (Formula (II)) and prodrugs therefor (Formula (I)), methods for their preparation, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in therapy and treatment, for example, of cancer, wherein: R1 and R2 are independently —Cl, —Br, —I, —OSO2CH3, or —OSO2Ph; R1a, R2a, R1b, and R2b are independently —H, a C1-4alkyl group, or a C1-4haloalkyl group; R3 is —F, —Cl, —Br, —I, —OCHF2, —C?CH, —OCF3, —CH3, —CF3, —SF5, —SCF3, or —CF2CF3; R4 is —H or as defined for R3?, R5 is —H or —F; R7 is —H, —C(CH3)3, or —CH2—CH—CH2; Z is —CH2—T—W; T is —CH2—, —O—, —S—, —(S?O)—, or —(SO2)—; W is one of: (1) —COOH; (2)—(C?O)OR8; (3) —(C?O)NR9R9; (4) —SO2NHR10?, (5) SO2OR11; (6)—PO3R11R11; (7) a tetrazol-5-yl group; (8) —CONH—SO2R12; and, (9)-M-Het.

Abstract: A range is disclosed of pyrimidine derivatives (I) which can act as inhibitors of cyclin dependent kinases (CDK's) and which thereby can provide useful therapeutic compounds for use in treatment of tumours or other cell proliferation disorders. The compounds of this invention bind to CDK molecules in a manner that appears to differ from that of known CDK inhibitors such as olomoucine and roscovitine.

Abstract: Determination of cellular growth abnormality, particularly cancerous abnormality, by detection of target polypeptides or encoding mRNA, where the target polypeptides are members of the preinitiation complex of DNA replication in tissue, cells or fluid. Target polypeptides include CDC6, MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7. Test samples include tissue of the cervix (both biopsy and smear samples), breast, colon, lung, bladder, skin, larynx, oesophagus, bronchus, lymph nodes and urinary tract (both biopsy and cytology smear samples), in determination of cancerous and precancerous cellular growth abnormality, and cells spun from urine, blood and serum, in determination of haematological malignancies and evidence of metastatic sarcoma and carcinoma.

Abstract: The invention relates to improvements in cell-free systems for initiating DNA replication under cell cycle control. The system comprises a synchronous population of G1 nuclei which have been released from G0; and S phase cytosol. In a preferred aspect, a polypeptide is supplied to the system, wherein the polypeptide is Cdc6 and/or at least one MCM protein. The system is suitable for DNA replication assays, for example to test substances which modulate DNA replication.

Abstract: The L2 protein of papillomavirus (particularly BPV-2 and BPV-4) has been cloned as a fusion protein with beta-galactosi-dase and GST; both as the whole protein and as fragments. Vaccination of calves is found to have both a prophylactic effect in tumor prevention and a therapeutic effect in tumor regression.

Abstract: The L2 protein of papillomavirus (particularly BPV-2 and BPV-4) has been cloned as a fusion protein with beta-galactosidase and GST; both as the whole protein and as fragments. Vaccination of calves is found to have both a prophylactic effect in tumour prevention and a therapeutic effect in tumour regression.

Abstract: Method of treating a tumour or other cell proliferation disorder which comprises administering an effective amount of a purine compound which inhibits cyclic dependent kinase activity. Novel purine compounds and pharmaceutical compositions are also disclosed.

Abstract: Determination of cellular growth abnormality, particularly cancerous abnormality, by detection of target polypeptides or encoding mRNA, where the target polypeptides are members of the preinitiation complex of DNA replication in tissue, cells or fluid. Target polypeptides include CDC6, MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7. Test samples include tissue of the cervix (both biopsy and smear samples), breast, colon, lung, bladder, skin, larynx, oesophagus, bronchus, lymph nodes and urinary tract (both biopsy and cytology smear samples), in determination of cancerous and pre-cancerous cellular growth abnormality, and cells spun from urine, blood and serum, in determination of haematological malignancies and evidence of metastatic sarcoma and carcinoma.

Abstract: Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs are substrates for carboxypeptidase G2 (CPG2) and yield more active cytotoxic drugs than known products of CPG2 catalysed reactions.

Abstract: Nucleic acid encoding subunits of a polypeptide folding complex containing TCp-1 is useful in expression of the subunits for assembly of the complex in vitro or in vivo. The complex promotes folding of polypeptides, such as tubulin, e.g., following recombinant expression. The sequences share a high degree of homology but the C-termini are sufficiently different to enable peptides with sequences derived therefrom to be used in obtaining antibodies specific for the various subunits, i.e., able to distinguish between them. The antibodies may be used in analysis and design of complexes able to fold different polypeptides.

Abstract: A compound which is a 6-substituted seco indoline of the formula (I): wherein: X is halogen or OSO2R where R represents H or C1-5 alkyl optionally substituted with from 1 to 4 hydroxyl, acid (COOH) or amino groups which amino may be optionally substituted by one or two C1-5 alkyl groups; Y is N02, N3, NHOH, NHR, NRR, N═NR, N(O)RR, SR or SSR, where R is defined as above, but that in the case where Y is SSR or N═NR, then R can also be another moiety of formula (I); or Y is a group of formula:

Abstract: The N-terminal region of bovine papillomavirus (BPV-4) L2 protein includes three immunogenically active epitopes. Two of these epitopes have substantial sequence homology to human papillomavirus (HPV) types. The BPV and HPV sequences are used to produce vaccine formulations for use in cattle and humans.

Abstract: The invention relates to new expression systems and in particular to an expression system in which a gene of interest is expressed at an optimal level. The invention provides a recombinant expression vector comprising a gene of interest and a selectable marker gene, wherein the selectable marker gene is arranged downstream of the gene of interest and a stop codon associated with the gene of interest is spaced from a start codon of said selectable marker gene at a distance which is sufficient to ensure that translation reinitiation is required before said selectable marker protein is expressed from the corresponding mRNA. Examples of such expression systems are vector viral packaging cell lines and a number of preferred cell lines have been identified.

Abstract: The invention provides compounds of general formula (I), wherein: X is halogen or OSO.sub.2 R, where R represents H or is unsubstituted or hydroxy-or amino-substituted lower alkyl; Y is a nitro or amine group or a substituted derivative thereof; W is selected from the structures of formulae (Ia, Ib or Ic), where E is --N.dbd. or --CH.dbd., G is O, S, or NH, and Q is either up to three of R, OR, NRR, NO.sub.2, CONHR, NHCOR or NHCONHR, or is an additional group of formulae (Ia, Ib or Ic) and HET represents a 5- or 6-membered carbocycle or heterocycle; and A and B collectively represent a fused benzene or 2-CO.sub.2 R pyrrole ring. In one embodiment, the group Y is an amine derivative substituted by a group which is a substrate for a nitroreductase or carboxypeptidase enzyme such that one of said enzymes is able to bring about removal of that group.

Abstract: A cell-free system for initiating DNA replication under cell cycle control includes S phase cytosol or a fraction thereof in which are incubated G1 phase nuclei, which are co-incubated with S phase nuclei or a fraction thereof and/or cyclins A and/or E complexed to their cognate cyclin dependent kinase (Cdk2). The system may be used to assay for substances which modulate DNA synthesis or initiation thereof, and which have therapeutic potential in a number of contexts.

Abstract: The present invention provides certain 6-hetarylalkyloxy pyrimidine derivatives of formula II ##STR1## wherein R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hetero atom chosen from O, N, or S, or a substituted derivative thereof; or (ii) phenyl or a substituted derivative thereof,R.sup.2 is selected from H, C.sub.1 -C.sub.5 alkyl, halogen or NH.sub.2,R.sup.4 and R.sup.5 which are the same or different are selected from H, NH.sub.2 or NO.sub.n where n=1 or 2, or R.sup.4 and R.sup.5 together with the pyrimidine ring form a 5- or 6-membered ring structure containing one or more heterocyclic atoms, and pharmaceutically acceptable salts thereof, exhibit the ability to deplete O.sup.6 -alkylguanine-DNA alkyltransferase (ATase) activity.