Abstract: The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

Abstract: The present invention relates to a compound of formula I wherein (i) when a and c are double bonds, R2 is absent, b is a single bond, R1 is or (ii) when a and c are single bonds, b is a double bond, and R1 is H, R2 is wherein the substituents are as defined in the specification.

Abstract: The present invention relates to compounds of formula I, or pharmaceutically acceptable salts thereof, wherein R1 and R5 are each independently H, C(ORj?) or a hydrocarbyl group optionally substituted by one or more R6 groups; R2, R3, and R4 are each independently H, alkyl or alkenyl, each of which may be optionally substituted with one or more R7 groups; R6 and R7 are each independently halogen, NO2, CN, (CH2)mORa, O(CH2)nORb, (CH2)pNRcRd, CF3, COORe, CONRfRg, CORh, SO3H, SO2Ri, SO2NRjRk, (CH2)qNRa?CORg?, Rf?, (CH2)rNRb?SO2Rh?, SO2NRd?Ri?, SO2NRe?(CH2)sORc?, heterocycloalkyl or heteroaryl, wherein said heterocycloalkyl and heteroaryl may be optionally substituted by one or more substituents selected from aralkyl, sulfonyl, Rm and CORn; Rg?, Rh?, Ri? and Rj? are each independently selected from alkyl, aryl, aralkyl and heteroaryl, each of which may be optionally substituted with one or more substituents selected from halogen, OH, NO2, NH2 CF3 and COOH; m, p, q and r are each independently 0, 1, 2 or 3

Abstract: The present invention relates to compounds of formula I, or pharmaceutically acceptable salt thereof, wherein: Z is CR10 or N; one of R1 and R2 is selected from (CH2)mR11, (CH2)mR12, (CH2)mNR12R13, (CH2)mOR12, (CH2)mNR13CO(CH2)nR11, (CH2)mNR13COR12, (CH2)mCONR13(CH2)nR11, (CH2)mCONR12R13, (CH2)mCO(CH2)nR11 and (CH2)mCOR12; where m is 0, 1, 2, 3 or 4 and n is 1, 2, 3 or 4; the other of R1 and R2 is H or R11; R3 and R5 are both H; R4 is H or R11; R6is H or (CH2)pR11, where p is 0 or 1; R7, R9 and R10 are each independently H or R11; R8 is selected from H, halogen, NO2, CN, OR13, NR13R14, NHCOR13, CF3, COR13, R13, CONR13R15, SO2NR13R14, SO2R13, NR13SO2R14, OCH2CH2OH, OCH2CH2OMe, morpholine, piperidine, and piperazine; each R11 is independently halogen, NO2, CN, (CH2)qOR13(CH2)rNR13R14, NHCOR13, CF3, COR13, R13, CONR13R14, SO2NR13R14, SO2R13, OR12, NR13SO2R14, OCH2CH2OH, OCH2CH2OMe, NR13SO2R12, (CH2)sNR12R13, morpholine, piperidine or piperazine, where q, r and s are each independently 0, 1, 2, 3 or

Abstract: The present invention relates to p21 derived peptides capable of inhibiting CDK/cyclin complexes, particularly cyclins A or E/CDK2, by modifying the interaction with their substrates. The peptides are derived from a C-terminal region of p21 and display selectivity for cyclin/CDK2 inhibition over cyclin/CDK4 inhibition. Variants of such peptides particularly involving certain alanine replacements are shown to be particularly potent.

Abstract: The invention relates to modified and truncated forms of the membrane transport vector penetratin. Such truncated forms include 7-mer peptides that may in themselves include further variation.

Abstract: A compound of formula 1, or a pharmaceutically acceptable salt thereof, wherein: X is S, O, or NH; “a” is a single bond; or “a” is a double bond and one of R3 and R4, and one of R5 and R6 are absent; R1 is H; or is selected from an alkyl group, a cycloalkyl group, a heteroaryl group, an aralkyl group, CO-alkyl, SO2-alkyl, CO2R13 and an aryl group, each of which optionally contains one or more heteroatoms, and is optionally substituted with one or more groups selected from R8 and R9; R2 is H, R8, or an alkyl group optionally substituted with one or more R8 groups; R3, R4, R5, and R6 are each independently selected from H, R8, an alkyl group and an alkenyl group, wherein said alkyl and alkenyl groups are optionally substituted with one or more R8 groups; or R3 and R4, and/or R5 and R6 together represent ?O; R7 is H, R8, NH(CH2)nR9, CO(CH2)nR9, NHCO(CH2)nR9, O(CH2)nR9, or an alkyl or phenyl group, each of which is optionally substituted with one or more groups selected from R8 and R9; R8 is OR10, NR10R11, h

Abstract: The present invention relates to compounds of formula I, or pharmaceutically acceptable salts thereof, wherein: (A) “a” is a single bond and “b” is a double bond; R1 and R2 are each independently as defined below; R10 is absent; or (B) “a” is a double bond and “b” is a single bond; R1 is oxygen; R2 is as defined below; and R10 is H or alkyl; X is S, O, NH, or NR7; Y is N or CR8; one of Z1, Z2, and Z3 is N or N+Ra and the remainder are each independently CR7; R1, R2, R5 and R6 are each independently R7; R3 and R4 are each independently R8; each R7 is independently H, halogen, NRbRc, ORd or a hydrocarbyl group optionally substituted by one or more R9 groups; each R8 is independently H or (CH2)nR9, where n is 0 or 1; each R9 is independently selected from H, halogen, NO2, CN, Re, NHCORf, CF3, CORg, NRhRi, CONRjRk, SO2NRlRm, SO2Rn, ORp, OCH2CH2ORq, morpholine, piperidine and piperazine; and Ra-q are each independently H or alkyl, wherein said alkyl group is optionally substituted by one or more R9 g

Abstract: The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

Abstract: The invention relates to modified and truncated forms of the membrane transport vector penetratin. Such truncated forms include 7-mer peptides that may in themselves include further variation.

Abstract: The present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in therapy. Prefereably, the compound may be used for treating a patient suffering from leukaemia, cancer or other proliferative disorder. A further embodiment relates to the use of a compound of formula (I) in an assay for detecting the phosphorylation and acetylation state of cellular substrates. The present invention also relates to novel compounds of formula (Ia).

Abstract: A first aspect of the invention relates to a combination comprising a CDK inhibitor and CPT-11. A second aspect of the invention relates to a pharmaceutical product comprising a CDK inhibitor and CPT-11 as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a CDK inhibitor and CPT-11 to a subject.

Abstract: The present invention relates to a novel drug delivery system of use in the improved delivery of drug therapeutic agents into target cells. The system comprises a drug moiety linked to a carrier moiety wherein the carrier moiety comprises a homeobox peptide or a fragment or derivative thereof.

Abstract: A first aspect of the invention relates to a combination comprising docetaxel, or a derivative or prodrug thereof, and a CDK inhibitor. A second aspect of the invention relates to a pharmaceutical product comprising docetaxel, or a derivative or prodrug thereof, and a CDK inhibitor as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a docetaxel, or a derivative or prodrug thereof, and a CDK inhibitor to a subject.

Abstract: A first aspect of the invention relates to a combination comprising a CDK inhibitor and cisplatin. A second aspect of the invention relates to a pharmaceutical product comprising a CDK inhibitor and cisplatin as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a CDK inhibitor and cisplatin to a subject.

Abstract: A first aspect of the invention relates to a combination comprising a CDK inhibitor and gemcitabine. A second aspect of the invention relates to a pharmaceutical product comprising a CDK inhibitor and gemcitabine as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a CDK inhibitor and gemcitabine to a subject.

Abstract: A first aspect of the invention relates to a combination comprising a CDK inhibitor and mitoxantrone. A second aspect of the invention relates to a pharmaceutical product comprising a CDK inhibitor and mitoxantrone as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a CDK inhibitor and mitoxantrone to a subject.

Abstract: p21WAF1 interacts with cyclin D1 and Cdk4. Peptide fragments of p21 inhibit the interaction and/or affect Cdk4 activity. The peptides, derivative peptides and non-peptidyl mimetics thereof are useful in affecting activity of Cdk4, such as RB phosphorylation, and cellular proliferation, indicative of therapeutic usefulness in treatment of tumours and other hyperproliferative disorders. Assay and screening methods allow identification of such modulators, especially inhibitors, of Cdk4 activity.

Abstract: A first aspect of the invention relates to a combination comprising a CDK inhibitor and doxorubicin. A second aspect of the invention relates to a pharmaceutical product comprising a CDK inhibitor and doxorubicin as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a CDK inhibitor and doxorubicin to a subject.

Abstract: The present invention relates to the use of bisarylsulfonamide compounds of formula I wherein W is a C1-5 branched or unbranched alkyl group or a C2-5 alkenyl group; n is 0 or 1; R1 is H, a C1-8 branched or unbranched alkyl group, a C2-8 alkenyl group, or an aryl or aralkyl group; Ar1 is a substituted thienyl, furyl, pyrrolyl, imidazothiazolyl, thiazolyl, pyridyl or phenyl group; and Ar2 is a substituted phenyl, indolyl or benzoimidazolyl group; in the preparation of a medicament for treating proliferative disorders. Further aspects of the invention relate to compounds of formula I, pharmaceutical compositions thereof, and an assay for determining binding to HDM2.