Target Information
Target General Information | Top | |||||
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Target ID |
T70176
(Former ID: TTDC00088)
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Target Name |
Cyclin-dependent kinase 2 (CDK2)
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Synonyms |
Sin3 associated polypeptide; SIN3-associated protein; P33 protein kinase; Cell division protein kinase 2; CDKN2
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Gene Name |
CDK2
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 8 Target-related Diseases | + | ||||
1 | Thymoma [ICD-11: 2C27] | |||||
2 | Brain cancer [ICD-11: 2A00] | |||||
3 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
4 | Lung cancer [ICD-11: 2C25] | |||||
5 | Lymphoma [ICD-11: 2A80-2A86] | |||||
6 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
7 | Non-small cell lung cancer [ICD-11: 2C25] | |||||
8 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1. Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability. Phosphorylates CDK2AP2. Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis.
Click to Show/Hide
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BioChemical Class |
Kinase
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UniProt ID | ||||||
EC Number |
EC 2.7.11.22
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Sequence |
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH
PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T75H3W |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 13 Clinical Trial Drugs | + | ||||
1 | PHA848125 | Drug Info | Phase 2 | Thymic cancer | [2], [3] | |
2 | R-roscovitine | Drug Info | Phase 2 | Non-small-cell lung cancer | [4], [5] | |
3 | Ro 31-7453 | Drug Info | Phase 2 | Solid tumour/cancer | [6] | |
4 | TG02 | Drug Info | Phase 1/2 | Anaplastic astrocytoma | [7], [8] | |
5 | AG-024322 | Drug Info | Phase 1 | Solid tumour/cancer | [9] | |
6 | AT7519 | Drug Info | Phase 1 | Solid tumour/cancer | [10] | |
7 | AZD-5438 | Drug Info | Phase 1 | Solid tumour/cancer | [11], [12] | |
8 | CYC065 | Drug Info | Phase 1 | Lymphoma | [7] | |
9 | FN-1501 | Drug Info | Phase 1 | Solid tumour/cancer | [13] | |
10 | PF-07104091 | Drug Info | Phase 1 | Triple negative breast cancer | [14] | |
11 | PHA-793887 | Drug Info | Phase 1 | Solid tumour/cancer | [15] | |
12 | RGB-286638 | Drug Info | Phase 1 | Haematological malignancy | [16], [17] | |
13 | SNS-032 | Drug Info | Phase 1 | Solid tumour/cancer | [18], [19] | |
Discontinued Drug(s) | [+] 5 Discontinued Drugs | + | ||||
1 | SCH 727965 | Drug Info | Discontinued in Phase 3 | Acute lymphoblastic leukaemia | [20], [21], [22] | |
2 | BAY 10-00394 | Drug Info | Discontinued in Phase 2 | Small-cell lung cancer | [23], [24] | |
3 | R547 | Drug Info | Discontinued in Phase 1 | Advanced solid tumour | [25], [26] | |
4 | ZK 304709 | Drug Info | Discontinued in Phase 1 | Advanced solid tumour | [27] | |
5 | PD-0183812 | Drug Info | Terminated | Retinoblastoma | [30] | |
Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
1 | INOC-005 | Drug Info | Preclinical | Solid tumour/cancer | [28] | |
2 | L-751250 | Drug Info | Preclinical | Obesity | [29] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 134 Inhibitor drugs | + | ||||
1 | PHA848125 | Drug Info | [31], [32] | |||
2 | R-roscovitine | Drug Info | [9], [33], [34] | |||
3 | Ro 31-7453 | Drug Info | [33] | |||
4 | AG-024322 | Drug Info | [9] | |||
5 | AT7519 | Drug Info | [36] | |||
6 | CYC065 | Drug Info | [7] | |||
7 | FN-1501 | Drug Info | [38] | |||
8 | PF-07104091 | Drug Info | [14] | |||
9 | PHA-793887 | Drug Info | [15] | |||
10 | RGB-286638 | Drug Info | [39] | |||
11 | SNS-032 | Drug Info | [19], [40] | |||
12 | 1,5-di-substituted pyridine derivative 1 | Drug Info | [41] | |||
13 | 4-(thiazol-5-yl)-pyrimidine derivative 1 | Drug Info | [41] | |||
14 | 4-(thiazol-5-yl)-pyrimidine derivative 2 | Drug Info | [41] | |||
15 | 4-amino-3,5-di-substituted-thiazole derivative 1 | Drug Info | [41] | |||
16 | 5-fluoro-N-(pyridin-2-yl)pyridin-2-amine derivative 1 | Drug Info | [41] | |||
17 | Alkyl sulfone derivative 1 | Drug Info | [41] | |||
18 | Aniline derivative 1 | Drug Info | [41] | |||
19 | Diamidothiazole derivative 1 | Drug Info | [41] | |||
20 | Diaryl amine derivative 1 | Drug Info | [41] | |||
21 | Flavopiridol analog 1 | Drug Info | [41] | |||
22 | Fluorinated compound 1 | Drug Info | [41] | |||
23 | Indole-based analog 11 | Drug Info | [41] | |||
24 | Indole-based analog 13 | Drug Info | [41] | |||
25 | Isoquinoline 1,3-dione derivative 1 | Drug Info | [41] | |||
26 | Isosteric imidazolyl pyrimidine derivative 1 | Drug Info | [41] | |||
27 | N-(pyridin-2-yl)pyridine methylsulfone derivative 1 | Drug Info | [41] | |||
28 | N-(pyridin-2-yl)pyrimidin-4-amine derivative 2 | Drug Info | [41] | |||
29 | N-phenyl-pyrimidin-4-amine derivative 1 | Drug Info | [41] | |||
30 | Naphthyridine and isoquinoline derivative 1 | Drug Info | [41] | |||
31 | Nitrogen mustard derivative 1 | Drug Info | [41] | |||
32 | Oxazolyl methylthiothiazole derivative 1 | Drug Info | [41] | |||
33 | Palbociclib/ribociclib analog 1 | Drug Info | [41] | |||
34 | PMID25991433-Compound-A1 | Drug Info | [42] | |||
35 | PMID26161698-Compound-25 | Drug Info | [41] | |||
36 | Pyrazolo-triazine derivative 2 | Drug Info | [41] | |||
37 | Pyrazolo[1,5-a]-1,3,5-triazine derivative 1 | Drug Info | [41] | |||
38 | Pyrrolo[2,3-d]pyrimidine derivative 9 | Drug Info | [41] | |||
39 | Roscovitine derivative 1 | Drug Info | [41] | |||
40 | SCH 727965 | Drug Info | [9] | |||
41 | BAY 10-00394 | Drug Info | [43] | |||
42 | R547 | Drug Info | [9] | |||
43 | ZK 304709 | Drug Info | [9] | |||
44 | INOC-005 | Drug Info | [44] | |||
45 | L-751250 | Drug Info | [45] | |||
46 | Olomoucine | Drug Info | [45] | |||
47 | PD-0183812 | Drug Info | [46] | |||
48 | (2'Z,3'E)-5-Chloro-5'-chloro-indirubin-3'-oxime | Drug Info | [47] | |||
49 | (2'Z,3'E)-5-Chloro-5'-fluoro-indirubin-3'-oxime | Drug Info | [47] | |||
50 | (2'Z,3'E)-5-Chloro-5'-hydroxy-indirubin-3'-oxime | Drug Info | [47] | |||
51 | (2'Z,3'E)-5-Chloro-5'-methyl-indirubin-3'-oxime | Drug Info | [47] | |||
52 | (2'Z,3'E)-5-Fluoro-5'-chloro-indirubin-3'-oxime | Drug Info | [47] | |||
53 | (2'Z,3'E)-5-Fluoro-5'-fluoro-indirubin-3'-oxime | Drug Info | [47] | |||
54 | (2'Z,3'E)-5-Fluoro-5'-hydroxy-indirubin-3'-oxime | Drug Info | [47] | |||
55 | (2'Z,3'E)-5-Fluoro-5'-methoxy-indirubin-3'-oxime | Drug Info | [47] | |||
56 | (2'Z,3'E)-5-Fluoro-5'-methyl-indirubin-3'-oxime | Drug Info | [47] | |||
57 | (2'Z,3'E)-5-Nitro-5'-chloro-indirubin-3'-oxime | Drug Info | [47] | |||
58 | (2'Z,3'E)-5-Nitro-5'-fluoro-indirubin-3'-oxime | Drug Info | [47] | |||
59 | (2'Z,3'E)-5-Nitro-5'-hydroxy-indirubin-3'-oxime | Drug Info | [47] | |||
60 | (2'Z,3'E)-5-Nitro-5'-methoxy-indirubin-3'-oxime | Drug Info | [47] | |||
61 | (2'Z,3'E)-5-Nitro-5'-methyl-indirubin-3'-oxime | Drug Info | [47] | |||
62 | 1-Amino-6-Cyclohex-3-Enylmethyloxypurine | Drug Info | [48] | |||
63 | 10Z-Hymenialdisine | Drug Info | [45] | |||
64 | 2-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol | Drug Info | [49] | |||
65 | 2-Amino-6-Chloropyrazine | Drug Info | [48] | |||
66 | 2-ANILINO-6-CYCLOHEXYLMETHOXYPURINE | Drug Info | [50], [51] | |||
67 | 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione | Drug Info | [52] | |||
68 | 3,4-diphenyl-1H-pyrrole-2,5-dione | Drug Info | [52] | |||
69 | 3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol | Drug Info | [49] | |||
70 | 3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione | Drug Info | [52] | |||
71 | 3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione | Drug Info | [52] | |||
72 | 4-(2,4-Dimethyl-Thiazol-5-Yl)-Pyrimidin-2-Ylamine | Drug Info | [48] | |||
73 | 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol | Drug Info | [49] | |||
74 | 4-[(6-chloropyrazin-2-yl)amino]benzenesulfonamide | Drug Info | [50] | |||
75 | 4-[3-Hydroxyanilino]-6,7-Dimethoxyquinazoline | Drug Info | [53] | |||
76 | 5-hydroxynaphthalene-1-sulfonamide | Drug Info | [50] | |||
77 | 5-nitroindirubin-3'-oxime | Drug Info | [47] | |||
78 | 6-(3-Amino-benzyloxy)-9H-purin-2-ylamine | Drug Info | [54] | |||
79 | 6-(3-Methyl-benzyloxy)-9H-purin-2-ylamine | Drug Info | [54] | |||
80 | 6-(Cyclohex-3-enylmethoxy)-9H-purin-2-ylamine | Drug Info | [54] | |||
81 | 6-CYCLOHEXYLMETHOXY-2-(3'-CHLOROANILINO) PURINE | Drug Info | [50] | |||
82 | 6-Cyclohexylmethoxy-pyrimidine-2,4,5-triamine | Drug Info | [55] | |||
83 | 6-cyclohexylmethyloxy-2-(4'-hydroxyanilino)purine | Drug Info | [50], [51] | |||
84 | 6-O-Cyclohexylmethyl Guanine | Drug Info | [48], [56] | |||
85 | 9-Nitropaullone | Drug Info | [45] | |||
86 | aloisine | Drug Info | [57] | |||
87 | aloisine A | Drug Info | [58] | |||
88 | aminopurvalanol A | Drug Info | [59] | |||
89 | Benzyl-(9-isopropyl-9H-purin-6-yl)-amine | Drug Info | [60] | |||
90 | BMS-265246 | Drug Info | [61] | |||
91 | BMS-536924 | Drug Info | [62] | |||
92 | BOHEMINE | Drug Info | [60] | |||
93 | BX-795 | Drug Info | [63] | |||
94 | BX-912 | Drug Info | [63] | |||
95 | Cdk1/2 inhibitor III | Drug Info | [64] | |||
96 | Cdk4 inhibitor III | Drug Info | [65] | |||
97 | CVT-313 | Drug Info | [66] | |||
98 | Double Oxidized Cysteine | Drug Info | [48] | |||
99 | GW-8510 | Drug Info | [67] | |||
100 | Indirubin-3'-monoxime | Drug Info | [45] | |||
101 | Indirubin-5-sulfonate | Drug Info | [45] | |||
102 | JNJ-7706621 | Drug Info | [68] | |||
103 | K00024 | Drug Info | [69] | |||
104 | Lysine Nz-Carboxylic Acid | Drug Info | [48] | |||
105 | MERIOLIN 1 | Drug Info | [70] | |||
106 | MERIOLIN 2 | Drug Info | [70] | |||
107 | MERIOLIN 3 | Drug Info | [70] | |||
108 | MERIOLIN 4 | Drug Info | [70] | |||
109 | MERIOLIN 5 | Drug Info | [70] | |||
110 | MERIOLIN 6 | Drug Info | [70] | |||
111 | MERIOLIN 8 | Drug Info | [70] | |||
112 | N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE | Drug Info | [50] | |||
113 | N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide | Drug Info | [71] | |||
114 | N-(4-sulfamoylphenyl)-1H-indazole-3-carboxamide | Drug Info | [50] | |||
115 | N-(5-Cyclopropyl-1h-Pyrazol-3-Yl)Benzamide | Drug Info | [48] | |||
116 | N-phenyl-1H-pyrazole-3-carboxamide | Drug Info | [50] | |||
117 | NSC-625987 | Drug Info | [72] | |||
118 | NU-6027 | Drug Info | [55] | |||
119 | NU-6102 | Drug Info | [73] | |||
120 | NU6140 | Drug Info | [74] | |||
121 | Oxindole 95 | Drug Info | [45] | |||
122 | PF-228 | Drug Info | [75] | |||
123 | PHA-690509 | Drug Info | [76] | |||
124 | PHENYLAMINOIMIDAZO(1,2-ALPHA)PYRIDINE | Drug Info | [50] | |||
125 | PMID18986805C9b | Drug Info | [77] | |||
126 | PMID19115845C89S | Drug Info | [78] | |||
127 | Purvalanol A | Drug Info | [79] | |||
128 | PYRAZOLOPYRIDAZINE 1 | Drug Info | [80] | |||
129 | PYRAZOLOPYRIDAZINE 2 | Drug Info | [80] | |||
130 | RESCOVITINE | Drug Info | [81] | |||
131 | SCH-546909 | Drug Info | [66] | |||
132 | SU9516 | Drug Info | [45] | |||
133 | TRIAZOLOPYRIMIDINE | Drug Info | [50] | |||
134 | VER-54505 | Drug Info | [66] | |||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | TG02 | Drug Info | [35] | |||
2 | AZD-5438 | Drug Info | [37], [12] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7938). | |||||
REF 3 | ClinicalTrials.gov (NCT01011439) Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma. U.S. National Institutes of Health. | |||||
REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6035). | |||||
REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010117) | |||||
REF 6 | A phase 2 study of oral MKC-1, an inhibitor of importin-beta, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer. Invest New Drugs. 2012 Aug;30(4):1614-20. | |||||
REF 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 9 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | |||||
REF 10 | ClinicalTrials.gov (NCT02503709) Onalespib and CDKI AT7519 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery in National Cancer Institute (NCI). | |||||
REF 11 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8473). | |||||
REF 12 | AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66. | |||||
REF 13 | ClinicalTrials.gov (NCT03690154) A Phase 1 Study to Evaluate FN-1501 Monotherapy in Patients With Advanced Solid Tumors and R/R AML. U.S. National Institutes of Health. | |||||
REF 14 | ClinicalTrials.gov (NCT04553133) PF-07104091 as a Single Agent and in Combination Therapy. U.S. National Institutes of Health. | |||||
REF 15 | A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70. | |||||
REF 16 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7744). | |||||
REF 17 | ClinicalTrials.gov (NCT01168882) Safety and Tolerability of RGB-286638 in Patients With Selected, Relapsed or Refractory Hematological Malignancies. U.S. National Institutes of Health. | |||||
REF 18 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5670). | |||||
REF 19 | Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45. | |||||
REF 20 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7379). | |||||
REF 21 | Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015 Jan 15;125(3):443-8. | |||||
REF 22 | Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models. Cancer Biol Ther. 2011 Oct 1;12(7):598-609. | |||||
REF 23 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7874). | |||||
REF 24 | BAY 1000394, a novel cyclin-dependent kinase inhibitor, with potent antitumor activity in mono- and in combination treatment upon oral application. Mol Cancer Ther. 2012 Oct;11(10):2265-73. | |||||
REF 25 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5707). | |||||
REF 26 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018924) | |||||
REF 27 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022386) | |||||
REF 28 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022337) | |||||
REF 29 | Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60. | |||||
REF 30 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014130) | |||||
REF 31 | Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63. | |||||
REF 32 | The cyclin-dependent kinase inhibitor PHA-848125 suppresses the in vitro growth of human melanomas sensitive or resistant to temozolomide, and shows synergistic effects in combination with this triazene compound. Pharmacol Res. 2010 May;61(5):437-48. | |||||
REF 33 | A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. | |||||
REF 34 | Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin D1 expression in vivo. Cell Cycle. 2009 Sep 1;8(17):2802-9. | |||||
REF 35 | Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42. | |||||
REF 36 | Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009 Feb;8(2):324-32. | |||||
REF 37 | AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells.Int J Radiat Oncol Biol Phys.2012 Nov 15;84(4):e507-14. | |||||
REF 38 | Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518. | |||||
REF 39 | Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75. | |||||
REF 40 | Development of cell-cycle inhibitors for cancer therapy. Curr Oncol. 2009 Mar;16(2):36-43. | |||||
REF 41 | Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70. | |||||
REF 42 | c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72. | |||||
REF 43 | National Cancer Institute Drug Dictionary (drug id 770319). | |||||
REF 44 | What are next generation innovative therapeutic targets. J Pharmacol Exp Ther. 2009 Jul;330(1):304-15. | |||||
REF 45 | Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25. | |||||
REF 46 | Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16. | |||||
REF 47 | 5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity. J Med Chem. 2010 May 13;53(9):3696-706. | |||||
REF 48 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 49 | 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9. | |||||
REF 50 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 51 | Halogen bonding--a novel interaction for rational drug design J Med Chem. 2009 May 14;52(9):2854-62. | |||||
REF 52 | Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81. | |||||
REF 53 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
REF 54 | Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives. J Med Chem. 2002 Aug 1;45(16):3381-93. | |||||
REF 55 | 4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22. | |||||
REF 56 | Novel structural features of CDK inhibition revealed by an ab initio computational method combined with dynamic simulations. J Med Chem. 2006 Aug 24;49(17):5141-53. | |||||
REF 57 | Identification of binding specificity-determining features in protein families. J Med Chem. 2012 Mar 8;55(5):1926-39. | |||||
REF 58 | Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003 Jan 16;46(2):222-36. | |||||
REF 59 | A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. | |||||
REF 60 | Docking-based development of purine-like inhibitors of cyclin-dependent kinase-2. J Med Chem. 2000 Jun 29;43(13):2506-13. | |||||
REF 61 | A robust high-content imaging approach for probing the mechanism of action and phenotypic outcomes of cell-cycle modulators. Mol Cancer Ther. 2011 Feb;10(2):242-54. | |||||
REF 62 | Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43. | |||||
REF 63 | Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74. | |||||
REF 64 | 1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J Med Chem. 2005 Jun 30;48(13):4208-11. | |||||
REF 65 | 5-Arylamino-2-methyl-4,7-dioxobenzothiazoles as inhibitors of cyclin-dependent kinase 4 and cytotoxic agents. Bioorg Med Chem Lett. 2000 Mar 6;10(5):461-4. | |||||
REF 66 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1973). | |||||
REF 67 | Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7. | |||||
REF 68 | Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41. | |||||
REF 69 | Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors. J Med Chem. 2003 May 22;46(11):2027-30. | |||||
REF 70 | Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin com... J Med Chem. 2008 Feb 28;51(4):737-51. | |||||
REF 71 | Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity. J Med Chem. 2006 Jun 15;49(12):3563-80. | |||||
REF 72 | The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4. Clin Cancer Res. 1999 Dec;5(12):4279-86. | |||||
REF 73 | Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. J Med Chem. 2006 Sep 7;49(18):5470-7. | |||||
REF 74 | Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation. Mol Cancer Ther. 2005 Sep;4(9):1328-37. | |||||
REF 75 | Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52. | |||||
REF 76 | Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14621-6. | |||||
REF 77 | Imidazole pyrimidine amides as potent, orally bioavailable cyclin-dependent kinase inhibitors. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6486-9. | |||||
REF 78 | First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J Med Chem. 2009 Jan 22;52(2):293-307. | |||||
REF 79 | The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315. | |||||
REF 80 | N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular effi... J Med Chem. 2004 Sep 9;47(19):4716-30. | |||||
REF 81 | Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors. Eur J Med Chem. 2010 Mar;45(3):1158-66. |
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