Discovery and Characterisation of 2-Anilino-4-(thiazol-5-yl) pyrimidine Transcriptional CDK Inhibitors as Anticancer Agents

Discovery and Characterisation of 2-Anilino-4-(Thiazol-5-Yl)Pyrimidine Transcriptional Cdk Inhibitors as Anticancer Agents

MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVF
EFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYT
HEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF
PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL

CRYSTAL STRUCTURE OF CDK2 WITH INHIBITOR

CDK2 IN COMPLEX WITH A DISUBSTITUTED 2, 4 -BIS ANILINO PYRIMIDINE CDK4 INHIBITOR

IDENTIFICATION OF N-(4-PIPERIDINYL)-4-(2,6 -DICHLOROBENZOYLAMINO)-1H-PYRAZOLE-3- CARBOXAMIDE (AT7519), A NOVEL CYCLIN DEPENDENT KINASE INHIBITOR USING FRAGMENT-BASED X- RAY CRYSTALLOGRAPHY AND STRUCTURE BASED DRUG DESIGN.

HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH DIN-234325

CDK2 IN COMPLEX WITH A DISUBSTITUTED 4, 6 -BIS ANILINO PYRIMIDINE CDK4 INHIBITOR

CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH 3-{[(2,2-DIOXIDO-1,3-DIHYDRO-2- BENZOTHIEN-5-YL)AMINO]METHYLENE}-5-(1,3- OXAZOL-5-YL)-1,3-DIHYDRO-2H-INDOL-2-ONE

CYCLIN A BINDING GROOVE INHIBITOR H-ARG- ARG-LEU-ILE-PHE-NH2

CDK2/CYCLINA IN COMPLEX WITH AN 11-RESIDUE RECRUITMENT PEPTIDE FROM E2F

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THEINHIBITOR N-[4-(2,4-DIMETHYL- THIAZOL-5-YL)PYRIMIDIN-2-YL]-N'- HYDROXYIMINOFORMAMIDE

STRUCTURE OF CDK2-CYCLIN A WITH PHA-848125

HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 4- HYDROXYPIPERINDINESULFONYL-INDIRUBINE

REPLACE: A STRATEGY FOR ITERATIVE DESIGN OF CYCLIN BINDING GROOVE INHIBITORS

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 2-AMINO-6-(3'-METHYL- 2'-OXO)BUTOXYPURINE

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR NU2058

CYCLIN A BINDING GROOVE INHIBITOR H-ARG- ARG-LEU-ASN-(P-F-PHE)-NH2

CDK2/CYCLINA IN COMPLEX WITH AN 11-RESIDUE RECRUITMENT PEPTIDE FROM P27

THE STRUCTURE OF CYCLIN-DEPENDENT KINASE 2 (CDK2) INCOMPLEX WITH 4-[(6-AMINO-4- PYRIMIDINYL)AMINO]BENZENESULFONAMIDE

HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH DPH-042562

CDK2 COMPLEXED WITH N-METHYL-4-{[(2-OXO- 1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL] AMINO}BENZENESULFONAMIDE

CYCLIN A - CYCLIN-DEPENDENT KINASE 2 COMPLEX

DIFFERENTIAL BINDING OF INHIBITORS TO ACTIVE AND INACTIVE CDK2 PROVIDES INSIGHTS FOR DRUG DESIGN

CRYSTAL STRUCTURE OF THE HUMAN CDK2 COMPLEXED WITH THE TRIAZOLOPYRIMIDINE INHIBITOR

1ST PUBLICATION TRUNCATION AND OPTIMISATION OF PEPTIDE INHIBITORS OF CDK2, CYCLIN A THROUGH STRUCTURE GUIDED DESIGN 2ND PUBLICATION DESIGN, SYNTHESIS AND EVALUATION OF 2-METHYL- AND 2-AMINO-N-ARYL-4,5- DIHYDROTHIAZOLO (4,5-H)QUINAZOLIN-8-AMINES AS RING-CONSTRAINED 2-ANILINO-4-(THIAZOL-5 -YL)PYRIMIDINE CDK INHIBITORS

THE STRUCTURE OF CYCLIN DEPENDENT KINASE 2 (CKD2) WITH ATRISUBSTITUTED NAPHTHOSTYRIL INHIBITOR

STRUCTURE OF CDK2-CYCLIN A WITH PHA-533514

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/ CYCLIN A COMPLEXED WITH THE INHIBITOR NU6094

CRYSTALS STRUCTURE OF HUMAN CDK2 IN COMPLEX WITH THE INHIBITOR OLOMOUCINE.

STRUCTURE OF CDK2 IN COMPLEX WITH AN IMIDAZOLYL PYRIMIDINE, COMPOUND 5B

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THEINHIBITOR [4-(2-AMINO-4-METHYL- THIAZOL-5-YL)-PYRIMIDIN-2-YL]-(3-NITRO- PHENYL)-AMINE

CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH 3-{[4-({[AMINO(IMINO)METHYL] AMINOSULFONYL)ANILINO]METHYLENE}-2-OXO-2,3- DIHYDRO-1H-INDOLE

HUMAN CDK2 IN COMPLEX WITH OLOMOUCINE II, A NOVEL 2,6,9-TRISUBSTITUTED PURINE CYCLIN -DEPENDENT KINASE INHIBITOR

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THEINHIBITOR 4-[4-(4-METHYL-2- METHYLAMINO-THIAZOL-5-YL)-PYRIMIDIN-2- YLAMINO]-PHENOL

CRYSTAL STRUCTURE OF HUMAN CDK2 COMPLEXED WITH A THIAZOLIDINONE INHIBITOR

IMIDAZOPYRIDINES: A POTENT AND SELECTIVE CLASS OF CYCLIN-DEPENDENT KINASE INHIBITORS IDENTIFIED THROUGH STRUCTURE-BASED HYBRIDISATION

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/ CYCLIN A COMPLEXED WITH THE INHIBITOR NU6086

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2- CYCLIN A F82H-L83V-H84D MUTANT WITH AN O6-CYCLOHEXYLMETHYLGUANINE INHIBITOR

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE CDK4INHIBITOR

APO STRUCTURE OF HUMAN CYCLIN-DEPENDENT KINASE 2

TRUNCATION AND OPTIMISATION OF PEPTIDE INHIBITORS OF CDK2, CYCLIN A THROUGH STRUCTURE GUIDED DESIGN

STRUCTURE OF CDK2 IN COMPLEX WITH AN IMIDAZOLYL PYRIMIDINE, COMPOUND 5C

PHOSPHORYLATED CYCLIN-DEPENDENT KINASE-2 BOUND TO CYCLIN A

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/ CYCLIN A COMPLEXED WITH A 6- CYCLOHEXYLMETHYLOXY-2-ANILINO-PURINE INHIBITOR

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THEINHIBITOR 3-[4-(2,4-DIMETHYL- THIAZOL-5-YL)-PYRIMIDIN-2-YLAMINO]-PHENOL

CRYSTAL STRUCTURE OF KINASE ASSOCIATED PHOSPHATASE (KAP) INCOMPLEX WITH PHOSPHO-CDK2

STRUCTURE OF CDK2/CYCLIN A WITH PNU-292137

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/ CYCLIN A COMPLEXED WITH THE INHIBITOR NU2058

STRUCTURAL AND THERMODYNAMIC CONSEQUENCES OF CYCLIZATION OF PEPTIDE LIGANDS FOR THE RECRUITMENT SITE OF CYCLIN A

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THEINHIBITOR 4-(2,5-DICHLORO-THIOPHEN- 3-YL)-PYRIMIDIN-2-YLAMINE

STRUCTURE OF CDK2-CYCLIN A WITH A PYRAZOLO (4,3-H) QUINAZOLINE-3-CARBOXAMIDE INHIBITOR

CRYSTAL STRUCTURE OF CDK2 WITH AN AMINOIMIDAZO PYRIDINEINHIBITOR

CDK2 IN COMPLEX WITH THE IMIDAZOLE PYRIMIDINE AMIDE, COMPOUND (S)-8B

SCREENING FOR FRAGMENT BINDING BY X-RAY CRYSTALLOGRAPHY

CRYSTAL STRUCTURE OF CDK2 IN COMPLEX WITH MACROCYCLIC AMINOPYRIMIDINE

STRUCTURE OF CDK2 COMPLEXED WITH PNU-181227

CRYSTAL STRUCTURE OF HUMAN CDK2 ( UNPHOSPHORYLATED) INCOMPLEX WITH PKF049-365

THE STRUCTURAL BASIS OF CDK2 ACTIVATION BY CYCLIN E

STRUCTURE OF CDK2-CYCLIN A COMPLEXED WITH 8-ANILINO-1-METHYL-4,5-DIHYDRO-1H- PYRAZOLO[4,3-H] QUINAZOLINE-3-CARBOXYLIC ACID

THE CRYSTAL STRUCTURE OF UCN-01 IN COMPLEX WITH PHOSPHO-CDK2/CYCLIN A

THE STRUCURE OF PHOSPHO-CDK2/CYCLIN A IN COMPLEX WITH THEINHIBITOR 4,5,6,7- TETRABROMOBENZOTRIAZOLE (TBS)

HUMAN CYCLIN DEPENDENT KINASE 2 (CKD2) COMPLEXED WITH DIN-232305

CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH N-METHYL-{4-[2-(7-OXO-6,7-DIHYDRO -8H-[1,3]THIAZOLO[5,4-E]INDOL-8- YLIDENE)HYDRAZINO]PHENYL}METHANESULFONAMIDE

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THEINHIBITOR 4-(2,4-DIMETHYL-THIAZOL- 5-YL)-PYRIMIDIN-2-YLAMINE

CRYSTAL STRUCTURE OF PHOSPHO-CDK2 CYCLIN A IN COMPLEX WITH A PEPTIDE CONTAINING BOTH THE SUBSTRATE AND RECRUITMENT SITES OF CDC6

STRUCTURE OF CDK2-CYCLIN A WITH PHA-404611

STRUCTURE OF THR 160 PHOSPHORYLATED CDK2/ CYCLIN A INCOMPLEX WITH THE INHIBITOR NU6271

CRYSTAL STRUCTURE OF HUMAN CDK2 COMPLEXED WITH A PYRAZOLO[1,5-A]PYRIMIDINE INHIBITOR

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2- CYCLIN A COMPLEXED WITH A BISANILINOPYRIMIDINE INHIBITOR

CDK2 COMPLEX WITH A 4-ALKYNYL OXINDOLE INHIBITOR

HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[(R )-PYRROLIDINO-5'-YL]METHOXYPURINE

CO-CRYSTAL STRUCTURE OF 6-CYCLOHEXYLMETHOXY- 8-ISOPROPYL-9H-PURIN-2-YLAMINE AND MONOMERIC CDK2

CRYSTAL STRUCTURE OF THE HUMAN CDK2 KINASE COMPLEX WITHCELL CYCLE-REGULATORY PROTEIN CKSHS1

STRUCTURE OF CDK2-CYCLIN A WITH PHA-630529

STRUCTURE OF CDK2 COMPLEXED WITH PNU-230032

THE STRUCTURE OF CDK2/CYCLIN A IN COMPLEX WITH AN OXINDOLEINHIBITOR

CYCLIN A BINDING GROOVE INHIBITOR AC-ARG- ARG-LEU-ASN-(M-CL-PHE)-NH2

HUMAN CYCLIN-DEPENDENT KINASE 2 IN COMPLEX WITH ROSCOVITINE

THE STRUCTURE OF CYCLIN-DEPENDENT KINASE 2 (CDK2) INCOMPLEX WITH AN OXINDOLE INHIBITOR

PHOSPHORYLATED CDK2-CYCLYIN A-SUBSTRATE PEPTIDE COMPLEX

FRAGMENT-BASED DISCOVERY OF THE PYRAZOL-4- YL UREA (AT9283), A MULTI-TARGETED KINASE INHIBITOR WITH POTENT AURORA KINASE ACTIVITY

DISCOVERY AND CHARACTERISATION OF 2-ANILINO- 4-(THIAZOL-5-YL)PYRIMIDINE TRANSCRIPTIONAL CDK INHIBITORS AS ANTICANCER AGENTS

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/ CYCLIN A COMPLEXED WITH A 2-ARYLAMINO-4- CYCLOHEXYLMETHYL-5-NITROSO-6-AMINOPYRIMIDINE INHIBITOR

HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2) COMPLEXED WITHINDENOPYRAXOLE DIN-101312

CRYSTAL STRUCTURE OF HUMAN CYCLIN-DEPENDENT KINASE 2COMPLEXED WITH A NUCLEOSIDE INHIBITOR

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/ CYCLIN A COMPLEXED WITH THE INHIBITOR NU6102

CRYSTAL STRUCTURE OF PHOSPHO-CDK2 IN COMPLEX WITH CYCLIN B

HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 5-BROMO- INDIRUBINE

CDK2 IN COMPLEX WITH AN IMIDAZO[1,2-B] PYRIDAZINE

CRYSTAL STRUCTURE OF MURINE GAMMA HERPESVIRUS CYCLIN COMPLEXED TO HUMAN CYCLIN DEPENDANT KINASE 2

CYCLIN A BINDING GROOVE INHIBITOR H-CIT- CIT-LEU-ILE-(P-F-PHE)-NH2

MECHANISM OF CDK INHIBITION BY ACTIVE SITE PHOSPHORYLATION: CDK2 Y15P T160P IN COMPLEX WITH CYCLIN A STRUCTURE

PCDK2/CYCLIN A IN COMPLEX WITH MGADP, NITRATE AND PEPTIDE SUBSTRATE

CDK2 IN COMPLEX WITH AN IMIDAZOLE PIPERAZINE

THE STRUCTURE OF CYCLIN-DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH 4-[3- HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE

OPTIMISATION OF 6,6-DIMETHYL PYRROLO 3,4- C PYRAZOLES: IDENTIFICATION OF PHA-793887, A POTENT CDK INHIBITOR SUITABLE FOR INTRAVENOUS DOSING

THR 160 PHOSPHORYLATED CDK2 - HUMAN CYCLIN A3 COMPLEX WITH THE INHIBITOR INDIRUBIN-5- SULPHONATE BOUND

HUMAN CYCLIN-DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR HYMENIALDISINE

CDK2/CYCLINA IN COMPLEX WITH A 9 RESIDUE RECRUITMENT PEPTIDE FROM E2F

HUMAN CDK2 IN COMPLEX WITH ISOPENTENYLADENINE

4-ARYLAZO-3,5-DIAMINO-1H-PYRAZOLE CDK INHIBITORS: SAR STUDY, CRYSTAL STRUCTURE IN COMPLEX WITH CDK2, SELECTIVITY, AND CELLULAR EFFECTS

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THEINHIBITOR N-[4-(2,4-DIMETHYL- THIAZOL-5-YL)-PYRIMIDIN-2-YL]-N',N'- DIMETHYL-BENZENE-1,4-DIAMINE

THE CRYSTAL STRUCTURE OF CDK2 CYCLIN A IN COMPLEX WITH A SUBSTRATE PEPTIDE DERIVED FROM CDC MODIFIED WITH A GAMMA-LINKED ATP ANALOGUE

HUMAN CYCLIN-DEPENDENT KINASE 2 PHOSPHORYLATED ON THR 160

STRUCTURE OF CDK2 COMPLEXED WITH PNU-198873

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR STAUROSPORINE

HUMAN CYCLIN DEPENDENT PROTEIN KINASE 2 IN COMPLEX WITH THE INHIBITOR 2-AMINO-6-[ CYCLOHEX-3-ENYL]METHOXYPURINE

CRYSTAL STRUCTURE OF HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2)IN COMPLEX WITH THE INHIBITOR H717

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR PURVALANOL B

CDK2/CYCLINA IN COMPLEX WITH AN 11-RESIDUE RECRUITMENT PEPTIDE FROM P107

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THEINHIBITOR [4-(2,4-DIMETHYL-THIAZOL- 5-YL)-PYRIMIDIN-2-YL]-(4-TRIFLUOROMETHYL- PHENYL)-AMINE

CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH 4-{[(2-OXO-1,2-DIHYDRO-3H-INDOL-3 -YLIDENE)METHYL]AMINO}-N-(1,3-THIAZOL-2- YL)BENZENESULFONAMIDE

CDK2/CYCLINA IN COMPLEX WITH AN 11-RESIDUE RECRUITMENT PEPTIDE FROM P53

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR NU6027

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. RESIDUES 340-42 ARE DISORDED. DISORDERED REGIONS WERE MODELED STEREOCHEMICALLY 13-18, 147-163.