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.


Anti-infection >
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2-Chloro-6-Methoxypurine-9-beta-D-(2'-deoxy-2'-fluoro)-arabinoriboside

2-Chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-6-methoxy-9H-purine 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: 758705-70-3
  • MF: C11H12ClFN4O4
  • MW: 318.69
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 547.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 285.2±32.9 °C

1,2,4-Triazine-3,5-dione 2-β-D-xylopyranoside

1,2,4-Triazine-3,5-dione 2-β-D-xylopyranoside 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: 93060-34-5
  • MF: C8H11N3O6
  • MW: 245.19
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC-Val-Cit-PAB-MMAF

MC-Val-Cit-PAB-MMAF is a drug-linker conjugate for ADC with antitumor activity by using the tubulin inhibitor, MMAF, linked via cathepsin cleavable MC-Val-Cit-PAB.

  • CAS Number: 863971-17-9
  • MF: C68H103N11O16
  • MW: 1330.61
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

garenoxacin mesylate

Garenoxacin (BMS 284756) mesylate is an orally active quinolone antibiotic and Garenoxacin mesylate has a broad spectrum of activity against a wide array of gram-positive and gram-negative bacteria, anaerobes. Garenoxacin mesylate also inhibits Gyrase and TOPO IV[1][2][3][4].

  • CAS Number: 223652-82-2
  • MF: C24H24F2N2O7S
  • MW: 522.52
  • Catalog: Bacterial
  • Density: 1.421g/cm3
  • Boiling Point: 581.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 305.5ºC

DJ101

A novel potent and metabolically stable tubulin inhibitor that can circumvent the drug efflux pumps responsible for multidrug resistance of existing tubulin inhibitors; demonstrates cytotoxicty in a panel of human metastatic melanoma cell lines harboring major clinically relevant mutations with IC50 of 7-10 nM, disrupts microtubule networks, suppresses anchorage-dependent melanoma colony formation, and impaires cancer cell migration; inhibits tumor growth and reduced lung metastasis in melanoma-bearing mice, also completely inhibits tumor growth in a paclitaxel-resistant xenograft mouse model.

  • CAS Number: 1803242-21-8
  • MF: C23H20N4O3
  • MW: 400.438
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aurora A inhibitor 2

Aurora A inhibitor 2 (Compound 16h) is a potent Aurora A kinase inhibitor with an IC50 of 21.94 nM. Aurora A inhibitor 2 induces caspase-dependent apoptosis in MDA-MB-231 cells[1].

  • CAS Number: 2412144-74-0
  • MF: C24H26N6O3
  • MW: 446.50
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-O-Acetyl-2,3,5-tri-O-benzoyl-6-deoxy-β-D-allofuranose

1-O-Acetyl-2,3,5-tri-O-benzoyl-5(R)-C-methyl-D-ribo furanose 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: 72159-45-6
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Fluorouracil-13C,15N2

5-Fluorouracil-13C,15N2 is the 13C and 15N labeled 5-Fluorouracil[1]. 5-Fluorouracil (5-FU) is an analogue of uracil and a potent antitumor agent. 5-Fluorouracil affects pyrimidine synthesis by inhibiting thymidylate synthetase thus depleting intracellular dTTP pools. 5-Fluorouracil induces apoptosis and can be used as a chemical sensitizer[2][3]. 5-Fluorouracil also inhibits HIV[4].

  • CAS Number: 1189423-58-2
  • MF: C313CH3F15N2O2
  • MW: 133.057
  • Catalog: HIV
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2′-Deoxy-6-O-methylinosine

2′-Deoxy-6-O-methylinosine 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: 37109-88-9
  • MF: C11H14N4O4
  • MW: 266.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IC 261

IC261 is a selective, ATP-competitive CK1 inhibitor, with IC50s of 1 μM, 1 μM, 16 μM for Ckiδ, Ckiε and Ckiα1, respectively.

  • CAS Number: 186611-52-9
  • MF: C18H17NO4
  • MW: 311.332
  • Catalog: Casein Kinase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 555.2±50.0 °C at 760 mmHg
  • Melting Point: 214 °C
  • Flash Point: 289.6±30.1 °C

1-[4-hydroxy-3-trityloxy-5-(trityloxymethyl)oxolan-2-yl]pyrimidine-2,4-dione

2',5'-Bis-O-(triphenylMethyl)uridine is a uridine analog. Uridine has potential antiepileptic effects, and its analogs can be used to study anticonvulsant and anxiolytic activities, as well as to develop new antihypertensive agents[1].

  • CAS Number: 6554-11-6
  • MF: C47H40N2O6
  • MW: 728.83
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.33g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2',3',5'-Tri-O-benzoyl-5-Methoxyuridine

2’,3’,5’-Tri-O-benzoyl-5-methoxyuridine 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: 37805-86-0
  • MF: C31H26N2O10
  • MW: 586.55
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Combretastatin A4 disodium phosphate

Fosbretabulin disodium(CA 4DP; CA 4P) is a microtubule destabilizing drug, a type of vascular-targeting agent, a drug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis.IC50 Value: 4 nM [1]Target: microtubulein vitro: Cytotoxic IC(50) values of CA-4 in human bladder cancer cells were below 4 nM. Analyses of cell-cycle distribution showed CA-4 obviously induced G(2)-M phase arrest with sub-G(1) formation. The analyses of apoptosis showed that CA-4 induced caspase-3 activation and decreased BubR1 and Bub3 in cancer cells [1]. The enhanced apoptosis induced by dasatinib plus CA-4 was accompanied by a greater extent of mitochondrial depolarization, caspase-3 activation and PARP cleavage in HO-8910 cells. Furthermore, elevated expression of Mcl-1 led to a reduced apoptosis induced by dasatinib plus CA-4, highlighting that downregulated Mcl-1 was necessary for the potentiating effect of dasatinib to CA-4-triggered apoptosis [2].in vivo: The increased anticancer efficacy of dasatinib combined with CA-4 was further validated in a human HO-8910 ovarian cancer xenograft model in nude mice [2]. There was a significant, concentration dependent increase in mean arterial blood pressure with a maximum increase of about 60% of the baseline MAP at 30 mg/kg of CA4P compared to the saline control. However, there was no significant increase in the cardiac troponin I level after CA4P injection [3].Clinical trial: A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome [4].

  • CAS Number: 168555-66-6
  • MF: C18H19Na2O8P
  • MW: 440.292
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: 611.8ºC at 760 mmHg
  • Melting Point: 238-242ºC
  • Flash Point: N/A

NU5455

NU5455 is a potent, selective, and orally active inhibitor of DNA-PKcs. NU5455 administration increases both the efficacy and the toxicity of a parenterally administered topoisomerase inhibitor. NU5455 enhances the activity of Doxorubicin released locally in liver tumor xenografts without inducing any adverse effect[1].

  • CAS Number: 1257235-99-6
  • MF: C34H33N3O5S
  • MW: 595.71
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Azidomethyl-2’-beta-methyl uridine

5-Azidomethyl-2’-beta-methyl uridine 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: 2305415-72-7
  • MF: C11H15N5O6
  • MW: 313.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5′-Deoxy-5′-iodo-5-methyluridine

5′-Deoxy-5′-iodo-5-methyluridine 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: 1884334-62-6
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rhodblock 6

Rhodblock 6 is a Rho kinase (ROCK) inhibitor that inhibits phospho-MRLC (myosin regulatory light chain) localization[1].

  • CAS Number: 886625-06-5
  • MF: C12H13N3O
  • MW: 215.25
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-4827 tosylate

Niraparib tosylate (MK-4827 tosylate) is an excellent PARP1 and PARP2 inhibitor with an IC50 of 3.8 and 2.1 nM, respectively.

  • CAS Number: 1038915-73-9
  • MF: C26H28N4O4S
  • MW: 492.59000
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Bromoquinazoline-2,4-diamine

DHFR-IN-3 is a dihydrofolate reductase (DHFR) inhibitor with the IC50 values of 19 μM and 12 μM in rat liver and P. carinii DHFR, respectively[1].

  • CAS Number: 137553-43-6
  • MF: C8H7BrN4
  • MW: 239.072
  • Catalog: Antifolate
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 509.4±58.0 °C at 760 mmHg
  • Melting Point: 255-256°C
  • Flash Point: 261.9±32.3 °C

ADTL-SA1215

ADTL-SA1215 is a first-in-class specific small-molecule activator of SIRT3 that modulates autophagy in triple negative breast cancer.

  • CAS Number: 782387-91-1
  • MF: C26H29I2NO3
  • MW: 657.32
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bendamustine

Bendamustine (SDX-105 free base), a purine analogue, is a DNA cross-linking agent. Bendamustine activates DNA-damage stress response and apoptosis. Bendamustine has potent alkylating, anticancer and antimetabolite properties[1].

  • CAS Number: 16506-27-7
  • MF: C16H21Cl2N3O2
  • MW: 358.263
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 585.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 307.7±30.1 °C

Antitumor agent-28

Antitumor agent-28 selectively inhibits ataxia telangiectasia mutated (ATM) kinase. Antitumor agent-28 prevents ATM mediated disease and has potent anti-cancer activity[1].

  • CAS Number: 2097499-67-5
  • MF: C25H32N6O4S
  • MW: 512.62
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DM4-SMe

DM4-SMe is a metabolite of antibody-maytansin conjugates (AMCs) and a tubulin inhibitor, and also a cytotoxic moiety of antibody-drug conjugates (ADCs), which can be linked to antibody through disulfide bond or stable thioether bond. DM4-SMe inhibits KB cells with an IC50 of 0.026 nM[1][2].

  • CAS Number: 796073-68-2
  • MF: C39H56ClN3O10S2
  • MW: 826.45900
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3’-Deoxy-3’-fluoro-N6-methyladenosine

3’-Deoxy-3’-fluoro-N6-methyladenosine 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: 122654-27-7
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pironetin

Pironetin is an α/β unsaturated lactone isolated from Streptomyces species. Pironetin binds to α-tubulin and is a potent inhibitor of microtubule polymerization, and has cell cycle arrest and antitumor activity[1][2].

  • CAS Number: 151519-02-7
  • MF: C19H32O4
  • MW: 324.45500
  • Catalog: Microtubule/Tubulin
  • Density: 0.993 g/cm3
  • Boiling Point: 473.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 160.3ºC

CAY10746

CAY10746 is a selective Rho kinase (ROCK) inhibitor. CAY10746 has inhibitory activity for ROCK I, ROCK II with IC50 values of 0.014 μM and 0.003 μM, respectively. CAY10746 can be used for the research of diabetic retinopathy (DR)[1].

  • CAS Number: 2247240-76-0
  • MF: C26H23N3O5
  • MW: 457.478
  • Catalog: ROCK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 664.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.5±31.5 °C

Topoisomerase I inhibitor 4

Topoisomerase I inhibitor 4 (compound 7a) is a topoisomerase I inhibitor. Topoisomerase I inhibitor 4 inhibits HepG2, A549, MCF-7 and HeLa cancer cells proliferation with IC50s of 1.20, 2.09, 1.56 and 1.92 μM, respectively. Topoisomerase I inhibitor 4 can be used for the research of cancer[1].

  • CAS Number: 2485135-31-5
  • MF: C23H19FN4O
  • MW: 386.42
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MF-094

MF-094 is a potent and selective USP30 inhibitor with an IC50 of 120 nM.

  • CAS Number: 2241025-68-1
  • MF: C30H37N3O4S
  • MW: 535.70
  • Catalog: Deubiquitinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5'-DMT-N2-DMF-dG

5'-O-DMT-2'-O-TBDMS-rI is a modified nucleoside. 5'-O-DMT-2'-O-TBDMS-rI can be used in the synthesis of deoxyribonucleic acid or nucleic acid.

  • CAS Number: 40094-22-2
  • MF: C34H36N6O6
  • MW: 624.68600
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDK2-IN-14-d3

CDK2-IN-14-d3 (compound 5f) is a potent and selective CDK2 inhibitor. CDK2-IN-14-d3 can be used in research of cancer[1].

  • CAS Number: 2498658-25-4
  • MF: C21H22D3N5O4S
  • MW: 446.54
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A