Cell Cycle includes many processes necessary for successful self-replication, and consists of DNA synthesis (S) and mitosis (M) phases separated by gap phases in the order G1–S–G2–M. S phase and M phase are usually separated by gap phases called G1 and G2, when cell-cycle progression can be regulated by various intracellular and extracellular signals. In order to move from one phase of its life cycle to the next, a cell must pass through numerous checkpoints. At each checkpoint, specialized proteins determine whether the necessary conditions exist. Progression through G1 phase is controlled by pRB proteins, and phosphorylation of pRB proteins by CDKs releases E2F factors, promoting the transition to S phase. The G2/M transition that commits cells to division is a default consequence of initiating the cell cycle at the G1/S transition, many proteins, such Wee1, PLK1 and cdc25, is involved the regulation of this process. The best-understood checkpoints are those activated by DNA damage and problems with DNA replication.

DNA damage response (DDR) is a series of regulatory events including DNA damage, cell-cycle arrest, regulation of DNA replication, and repair or bypass of DNA damage to ensure the maintenance of genomic stability and cell viability. Genome instability arises if cells initiate mitosis when chromosomes are only partially replicated or are damaged by a double-strand DNA break (DSB). To prevent cells with damaged DNA from entering mitosis, ATR inhibits cyclin B/Cdk1 activation by stimulating the Cdk1 inhibitory kinase Wee1 and inhibiting Cdc25C via Chk1, besides, ATM and ATR also initiate DNA repair by phosphorylating several other substrates.

In cancer cells, the cell cycle regulators as well as other elements of the DDR pathway have been found to protect tumor cells from different stresses and to promote tumor progression. Thus, cell cycle proteins that directly regulate cell cycle progression (such as CDKs), as well as checkpoint kinases, Aurora kinases and PLKs, are promising targets in cancer therapy.

References:
[1] Rhind N, et al. Cold Spring Harb Perspect Biol. 2012 Oct; 4(10): a005942.
[2] Duronio RJ, et al. Cold Spring Harb Perspect Biol. 2013 Mar; 5(3): a008904.
[3] Liu W, et al. Mol Cancer. 2017 Mar 14;16(1):60.
[4] Ghelli Luserna di Rora' A, et al. J Hematol Oncol. 2017 Mar 29;10(1):77.


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1-(β-D-Ribofuranosyl)-5-nitropyrine-2(1H)-one

1-(β-D-Ribofuranosyl)-5-nitropyrine-2(1H)-one is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 59892-36-3
  • MF: C10H12N2O7
  • MW: 272.21
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AAPK-25

AAPK-25 is a potent and selective Aurora/PLK dual inhibitor with anti-tumor activity, which can cause mitotic delay and arrest cells in a prometaphase, reflecting by the biomarker histone H3Ser10 phosphorylation and followed by a surge in apoptosis. AAPK-25 targets Aurora-A, -B, and -C with Kd values ranging from 23-289 nM, as well as PLK-1, -2, and -3 with Kd values ranging from 55-456 nM[1].

  • CAS Number: 2247919-28-2
  • MF: C21H13Cl2N3O2S
  • MW: 442.32
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T-2513 hydrochloride

T-2513 hydrochloride is a selective topoisomerase I inhibitor. T-2513 hydrochloride binds covalently to and stabilizes the topoisomerase I-DNA complex and inhibits DNA replication and RNA synthesis, ultimately leading to cell death[1].

  • CAS Number: 187793-52-8
  • MF: C25H28ClN3O5
  • MW: 485.96
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PPARδ/γ agonist 1

DB-959 (T3D-959 (free base)) is a potent dual PPAR delta/gamma inhibitor. DB-959 can be used for Alzheimer’s disease research[1].

  • CAS Number: 1257641-15-8
  • MF: C25H27NO5
  • MW: 421.49
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Chloro-2’-deoxy inosine

2-Chloro-2’-deoxy inosine is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 136834-39-4
  • MF: C10H11ClN4O4
  • MW: 286.67
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-METHYLGUANOSINE

7-Methylguanosine is a novel cNIIIB nucleotidase inhibitor with IC50 value of 87.8 ± 7.5 µM.

  • CAS Number: 20244-86-4
  • MF: C11H16N5O5+
  • MW: 298.27500
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 165ºC
  • Flash Point: N/A

SIRT1-IN-1

SIRT1-IN-1 is a selective SIRT1 inhibitor with an IC50 of 0.205 μM. SIRT1-IN-1 inhibits SIRT2 with an IC50 of 11.5 μM[1]. SIRT1-IN-1, a indole, is a cytomegalovirus (CMV) inhibitors and has antiviral activity[2].

  • CAS Number: 352554-02-0
  • MF: C14H16N2O
  • MW: 228.29
  • Catalog: CMV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Chloro-2',3'-dideoxy-3'-fluoro-uridine

Raluridine is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 119644-22-3
  • MF: C9H10ClFN2O4
  • MW: 264.64
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MPC-0767

MPC-0767 is a potent, selective, and orally active hsp90 inhibitor. MPC-0767 is an L-alanine ester prodrug of MPC-3100 with improved chemical stability[1].

  • CAS Number: 1310540-32-9
  • MF: C26H36BrN7O9S2
  • MW: 734.64
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Belinostat

Belinostat is a potent HDAC inhibitor with an IC50 of 27 nM in HeLa cell extracts.

  • CAS Number: 866323-14-0
  • MF: C15H14N2O4S
  • MW: 318.34800
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 160 °C(dec.)
  • Flash Point: N/A

2’,3’,5’-Tri-O-benzoyl-2’-β-C-methyl-5-methyl uridine

2’,3’,5’-Tri-O-benzoyl-2’-β-C-methyl-5-methyl uridine is a thymidine analog. Analogs of this series have insertional activity towards replicated DNA. They can be used to label cells and track DNA synthesis[1].

  • CAS Number: 957535-53-4
  • MF: C32H28N2O9
  • MW: 584.57
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/HER2/CDK9-IN-1

EGFR/HER2/CDK9-IN-1 (Compound 4) is a potent inhibitor of EGFR/HER2/CDK9 with IC50s of 90.17, 131.39, and 67.04 nM, respectively. EGFR/HER2/CDK9-IN-1 exhibits remarkable antitumor activity[1].

  • CAS Number: 879730-44-6
  • MF: C23H21N3O3S2
  • MW: 451.56
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Amino-6-chloropurine-3',5'-di-O-acetyl-2'-deoxyriboside

2-Amino-6-chloropurine-3’,5’-di-O-acetyl-2’-deoxyriboside is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 69992-11-6
  • MF: C14H16ClN5O5
  • MW: 369.76
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Amino-7,8-dihydro-8-oxo-9-(β-D-xylofuranosyl) guanine

1-Amino-7,8-dihydro-8-oxo-9-(β-D-xylofuranosyl) guanine is a purine nucleoside analogue. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 2389988-21-8
  • MF: C10H14N6O6
  • MW: 314.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubulin inhibitor 12

Tubulin inhibitor 12 (Hit 9) is a novel tubulin inhibitor (IC50=25.3 μM). Tubulin inhibitor 12 shows anti-tumor activity and anti-proliferative activity[1].

  • CAS Number: 92575-00-3
  • MF: C24H20N2O
  • MW: 352.43
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cytarabine

Cytarabine is a chemotherapy drug used to treat acute myeloid leukaemia, acting by inhibiting DNA synthesis with an IC50 of 16 nM.

  • CAS Number: 147-94-4
  • MF: C9H13N3O5
  • MW: 243.217
  • Catalog: Autophagy
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 529.7±60.0 °C at 760 mmHg
  • Melting Point: 214 °C
  • Flash Point: 274.1±32.9 °C

5-Amino-2'-deoxyuridine monohydrochloride

5-Amino-2'-deoxyuridine (monohydrochloride) is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 73446-40-9
  • MF: C9H14ClN3O5
  • MW: 279.68
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5'-TBDMS-Bz-dA

5'-O-TBDMS-Bz-dA is a nucleoside with protective and modification effects.

  • CAS Number: 51549-39-4
  • MF: C23H31N5O4Si
  • MW: 469.60900
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK2850163

GSK2850163 is a novel inhibitor of inositol-requiring enzyme-1 alpha (IRE1α) which can inhibit IRE1α kinase activity and RNase activity with IC50s of 20 and 200 nM, respectively.

  • CAS Number: 2121989-91-9
  • MF: C24H29Cl2N3O
  • MW: 446.41
  • Catalog: IRE1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PU-WS13

PU-WS13 is a selective Grp94 inhibitor, with an EC50 of 0.22 μM.

  • CAS Number: 1454619-14-7
  • MF: C17H20Cl2N6S
  • MW: 411.352
  • Catalog: HSP
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 617.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 327.2±34.3 °C

a-D-Xylofuranose,1,2-O-(1-methylethylidene)-, 5-benzoate

5-O-Benzoyl-1,2-di-O-isopropylidene-alpha-D-xylofuranose is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 6022-96-4
  • MF: C15H18O6
  • MW: 294.30
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 432.0±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 159.2±20.8 °C

Tubulin inhibitor 18

Tubulin inhibitor 18 (compound 5j) is a potent inhibitor of tubulin. Tubulin inhibitor 18 is a chalcone compound. Tubulin inhibitor 18 has the potential for the research of cancer diseases[1].

  • CAS Number: 2762382-51-2
  • MF: C22H26O5
  • MW: 370.44
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BTO-1

BTO-1 is a Polo-like kinase (Plk) inhibitor. BTO-1 is primarily used for phosphorylation and dephosphorylation applications[1][2].

  • CAS Number: 40647-02-7
  • MF: C9H4N4O4S
  • MW: 264.21700
  • Catalog: Polo-like Kinase (PLK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vinblastine

Vinblastine is a cytotoxic alkaloid used against various cancer types. Vinblastine inhibits the formation of microtubule and suppresses nAChR with an IC50 of 8.9 μM.

  • CAS Number: 865-21-4
  • MF: C46H58N4O9
  • MW: 810.974
  • Catalog: Microtubule/Tubulin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 211 - 216ºC
  • Flash Point: N/A

(2R-cis)-5-[Tetrahydro-5-(hydroxymethyl)-4-oxo-2-furanyl]-2,4(1H,3H)-pyrimidinedione

(2R-cis)-5-[Tetrahydro-5-(hydroxymethyl)-4-oxo-2-furanyl]-2,4(1H,3H)-pyrimidinedione is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 142189-87-5
  • MF: C9H10N2O5
  • MW: 226.19
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5'-DMT-N6-Me-2'-dA

5'-O-DMT-N6-Me-2'-dA is a nucleoside with protective and modification effects.

  • CAS Number: 98056-69-0
  • MF: C32H33N5O5
  • MW: 567.63500
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRPKIN-1

SRPK-IN-1 is a covalent and irreversible SRPK1/2 inhibitor with IC50s of 35.6 and 98 nM, respectively. Anti-angiogenesis effect[1].

  • CAS Number: 2089226-94-6
  • MF: C27H21FN2O3S
  • MW: 472.53
  • Catalog: SRPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DHODH-IN-14

DHODH-IN-14 (Compound 7l) is a hydroxyfurazan analog of A771726. DHODH-IN-14 is a dihydroorotate dehydrogenase (DHODH) inhibitor with an IC50 of 0.49 μM for rat liver DHODH. DHODH-IN-14 can be used for rheumatoid arthritis[1].

  • CAS Number: 1364791-93-4
  • MF: C15H7F4N3O3
  • MW: 353.23
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-[(2R,4S,5R)-5-(aminomethyl)-4-hydroxy-oxolan-2-yl]pyrimidine-2,4-dione

5′-Amino-2′,5′-dideoxyuridine is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].

  • CAS Number: 35959-38-7
  • MF: C9H13N3O4
  • MW: 227.22
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.466g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDK2 inhibitor 73

CDK2-IN-4 is a potent and selective CDK2 inhibitor with an IC50 of 44 nM for CDK2/cyclin A, shows 2,000-fold selectivity over CDK1/cyclin B (IC50=86 uM)[1].

  • CAS Number: 2079895-42-2
  • MF: C23H18N6O2S
  • MW: 442.49
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A