. "[B24B4DCD7F7F]" . . . "Activity; Antiproliferative; Kinases; Cyclin-Dependent; Inhibitor; Selective; Roscovitine; Bioisostere; Pyrazolo[4,3-d]pyrimidine"@en . "\u0160turc, Anton\u00EDn" . "Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity"@en . . "Inhibition of cyclin-dependent kinases (CDKs) with small molecules has been suggested as a strategy for treatment of cancer, based on deregulation of CDKs commonly found in many types of human tumors. Here, a new potent CDK2 inhibitor with pyrazolo[4,3-d]pyrimidine scaffold has been synthesized, characterized, and evaluated in cellular and biochemical assays. 7-Benzylamino-5(R)-[2-(hydroxymethyl)-propyl]amino-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyrimidine, compound 7, was prepared as a bioisostere of the well-known CDK inhibitor roscovitine. An X-ray crystal structure of compound 7 bound to CDK2 has been determined, revealing a binding mode similar to that of roscovitine. Protein kinase selectivity profile of compound 7 and its biological arrest, dephosphorylation of the retinoblastoma protein, accumulation of the tumor suppressor protein p53, induction of apoptosis, inhibition of homologous recombination) are consistent with CDK inhibition as a primary mode of action." . "225326" . "HAVL\u00CD\u010CEK, Libor" . . . "Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity" . . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . "12"^^ . "RIV/61989592:15310/11:10222088!RIV12-MZ0-15310___" . "Kuzma, Marek" . "JORDA, Radek" . . . "Kry\u0161tof, Vladim\u00EDr" . . . . "6"^^ . . . . . "10.1021/jm200064p" . "Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity" . "STRNAD, Miroslav" . "B\u00C1RTEK, Ji\u0159\u00ED" . . "P(ED0007/01/01), P(ED0030/01/01), P(GA204/08/0511), P(GA301/02/0475), P(GA301/08/1649), P(GPP301/11/P554), P(IAA501370902), P(NS10282), P(NT11065), Z(AV0Z50200510), Z(AV0Z50380511), Z(MSM6198959216)" . . . "000289697800033" . "Inhibition of cyclin-dependent kinases (CDKs) with small molecules has been suggested as a strategy for treatment of cancer, based on deregulation of CDKs commonly found in many types of human tumors. Here, a new potent CDK2 inhibitor with pyrazolo[4,3-d]pyrimidine scaffold has been synthesized, characterized, and evaluated in cellular and biochemical assays. 7-Benzylamino-5(R)-[2-(hydroxymethyl)-propyl]amino-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyrimidine, compound 7, was prepared as a bioisostere of the well-known CDK inhibitor roscovitine. An X-ray crystal structure of compound 7 bound to CDK2 has been determined, revealing a binding mode similar to that of roscovitine. Protein kinase selectivity profile of compound 7 and its biological arrest, dephosphorylation of the retinoblastoma protein, accumulation of the tumor suppressor protein p53, induction of apoptosis, inhibition of homologous recombination) are consistent with CDK inhibition as a primary mode of action."@en . . . . . . . . . "Walkinshaw, Malcolm" . . . . "McNae, Iain" . "14"^^ . . "VOLLER, Ji\u0159\u00ED" . "Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity"@en . "Journal of Medicinal Chemistry" . . "15310" . . "MISTR\u00CDK, Martin" . . . . "Navr\u00E1tilov\u00E1, Jana" . . . . "54" . "0022-2623" . "RIV/61989592:15310/11:10222088" . . "8" .