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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RO-3306

Ro-3306 is a potent and selective inhibitor of CDK1, with Kis of 20 nM, 35 nM and 340 nM for CDK1, CDK1/cyclin B1 and CDK2/cyclin E, respectively.

  • CAS Number: 872573-93-8
  • MF: C18H13N3OS2
  • MW: 351.445
  • Catalog: CDK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 569.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 298.0±32.9 °C

NCGC00029283

NCGC00029283 is a werner syndrome helicase-nuclease (WRN) helicase inhibitor with IC50s of 2.3 μM, 12.5 μM, and 3.4 μM for WRN, BLM and FANCJ helicase, respectively[1].

  • CAS Number: 714240-31-0
  • MF: C18H12FN3O3
  • MW: 337.305
  • Catalog: DNA/RNA Synthesis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 576.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 302.6±32.9 °C

LY2603618

LY2603618 is a potent and selective inhibitor of Chk1 with an IC50 of 7 nM.

  • CAS Number: 911222-45-2
  • MF: C18H22BrN5O3
  • MW: 436.303
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 503.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 258.1±30.1 °C

Dimethylenastron

Dimethylenastron is a potent Eg5 inhibitor, with an IC50 of 200 nM.

  • CAS Number: 863774-58-7
  • MF: C16H18N2O2S
  • MW: 302.391
  • Catalog: Kinesin
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 475.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 241.4±31.5 °C

Ribociclib (LEE011)

Ribociclib (LEE011) is a highly specific CDK4/6 inhibitor with IC50s of 10 nM and 39 nM, respectively.

  • CAS Number: 1211441-98-3
  • MF: C23H30N8O
  • MW: 434.537
  • Catalog: CDK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 730.8±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 395.8±35.7 °C

ARTD10/PARP10-IN-2

ARTD10/PARP10-IN-2 (compound 19) is a potent and non-selective PARP inhibitor, targeting to mono-ADP-ribosyltransferases ARTD10/PARP10 and poly(ADP-ribose) polymerase-1 ARTD1/PARP1 with IC50s of 2.0 μM, and 9.7 μM, respectively[1].

  • CAS Number: 1708103-69-8
  • MF: C12H13N3O3
  • MW: 247.25
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHR-3996

Nanatinostat (CHR-3996) is a potent, class I selective and orally active histone deacetylase (HDAC) inhibitor with an IC50 of 8 nM[1].

  • CAS Number: 1256448-47-1
  • MF: C20H19FN6O2
  • MW: 394.40
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2,2,6,6-Tetramethylpiperidinooxy

Tempo is a classic nitroxide radical and is a selective scavenger of mitochondrial ROS that dismutases superoxide in the catalytic cycle. Tempo induces DNA-strand breakage. Tempo can be used as an organocatalyst for the oxidation of primary alcohols to aldehydes. Tempo has mutagenic and antioxidant effects[1][2][3][4].

  • CAS Number: 2564-83-2
  • MF: C10H21NO?
  • MW: 156.245
  • Catalog: DNA/RNA Synthesis
  • Density: 1 g/cm3
  • Boiling Point: 193°C
  • Melting Point: 36-38 °C(lit.)
  • Flash Point: 154 °F

WRN inhibitor 2

WRN inhibitor 2 (example 118) is a WRN (Werner Syndrome ATP dependent helicase enzyme) inhibitor, with pIC50 ≥ 7.0[1].

  • CAS Number: 2923009-56-5
  • MF: C15H11F3N2O5S2
  • MW: 420.38
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OBP-801

Spiruchostatin A is a potent HDAC inhibitor with an IC50 value of 2 nM. Spiruchostatin A can induce apoptosis, has antitumor activity and may be used in leukemia studies[1][2].

  • CAS Number: 328548-11-4
  • MF: C20H31N3O6S2
  • MW: 473.607
  • Catalog: HDAC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 865.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 477.3±34.3 °C

Trimethoprim lactate

Trimethoprim lactic is a bacteriostatic antibiotic and an orally active dihydrofolate reductase inhibitor. Trimethoprim lactic is active against a wide range of Gram-positive and Gram-negative aerobic bacteria. Trimethoprim lactic has the potential for urinary tract infections, Shigellosis and Pneumocystis pneumonia treatment[1][2][3].

  • CAS Number: 23256-42-0
  • MF: C17H24N4O6
  • MW: 380.396
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: 526ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 271.9ºC

Pioglitazone hydrochloride

Pioglitazone hydrochloride is a potent and selective PPARγ agonist with EC50s of 0.93 and 0.99 μM for human and mouse PPARγ, respectively.

  • CAS Number: 112529-15-4
  • MF: C19H21ClN2O3S
  • MW: 392.900
  • Catalog: PPAR
  • Density: 1.26 g/cm3
  • Boiling Point: 575.4ºC at 760 mmHg
  • Melting Point: 193-194ºC
  • Flash Point: 301.8ºC

Remdesivir nucleoside monophosphate

Remdesivir nucleoside monophosphate is a metabolite of Remdesivir[1]. Remdesivir is a nucleoside analogue with effective antiviral activity against SARS-CoV and MERS-CoV[2].

  • CAS Number: 1911578-74-9
  • MF: C12H14N5O7P
  • MW: 371.24
  • Catalog: SARS-CoV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Topoisomerase I inhibitor 3

Topoisomerase I inhibitor 3 (Compound ZML-14) is a topoisomerase I inhibitor and can interact with topoisomerase I-DNA complex. Topoisomerase I inhibitor 3 induces HepG2 cell apoptosis and arrests cell cycle at G2/M phase[1].

  • CAS Number: 2588211-50-9
  • MF: C18H14FNO3
  • MW: 311.31
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TC-A 2317 hydrochloride

TC-A 2317 hydrochloride is an orally active Aurora A kinase inhibitor (Ki=1.2 nM). TC-A 2317 hydrochloride exhibits excellent selectivity to Aurora B kinase (Ki=101 nM) and other 60 kinases, good cell permeability and good PK profile. Antitumor activity[1].

  • CAS Number: 1245907-03-2
  • MF: C19H29ClN6O
  • MW: 392.92600
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Amino-1-(2-C-methyl-β-D-ribofuranosyl)-1H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

4-Amino-5-cyano-1-(2-β-C-methyl-β-D-ribofuranosyl)-7H-pyrrolo[2.3-d]pyrimidine 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: 847651-51-8
  • MF: C13H15N5O4
  • MW: 305.29
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD5438

AZD-5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM in cell-free assays. It also inhibits GSK3β, but is less potent to CDK5/6.

  • CAS Number: 602306-29-6
  • MF: C18H21N5O2S
  • MW: 371.457
  • Catalog: CDK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 655.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 350.1±34.3 °C

YM-01(YM-1)

YM-1 is a stable and soluble MKT-077 (HY-15096) analog and an orally active Hsp70 inhibitor. YM-1 induces cell death of HeLa cells and up-regulates the level of p53 and p21 proteins[1][2].

  • CAS Number: 409086-68-6
  • MF: C20H20ClN3OS2
  • MW: 417.975
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FRAX 597

FRAX597 is a potent group I p21-activated Kinases (PAKs) inhibitor with IC50 of 8, 13 and 19 nM for PAK1, 2 and 3.

  • CAS Number: 1286739-19-2
  • MF: C29H28ClN7OS
  • MW: 558.10
  • Catalog: PAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Ethyl-10-hydroxycamptothecin

SN-38 is an active metabolite of the Topoisomerase I inhibitor Irinotecan. SN-38 inhibits DNA and RNA synthesis with IC50s of 0.077 and 1.3 μM, respectively.

  • CAS Number: 86639-52-3
  • MF: C22H20N2O5
  • MW: 392.405
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 810.3±65.0 °C at 760 mmHg
  • Melting Point: 217 °C
  • Flash Point: 443.8±34.3 °C

N-2-Acetylguanine

N2-Acetylguanine is a C2-modified guanine. N2-Acetylguanine binds GR (guanine-guanine riboswitch) with an Kd value of 300 nM. N2-Acetylguanine modulate transcriptional termination. N2-Acetylguanine has the potential for the research of antimicrobial agent[1].

  • CAS Number: 19962-37-9
  • MF: C7H7N5O2
  • MW: 193.16300
  • Catalog: DNA/RNA Synthesis
  • Density: 1.83 g/cm3
  • Boiling Point: N/A
  • Melting Point: 260 °C
  • Flash Point: N/A

N4-BENZOYL-5'-O-(DIMETHOXYTRITYL)-3'-DEOXYCYTIDINE

N4-Benzoyl-5’-O-(4,4-dimethoxytrityl)-3’-deoxy cytidine 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: 86234-45-9
  • MF: C37H35N3O7
  • MW: 633.69
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

guanosine 5'-(tetrahydrogen triphosphate)

Guanosine triphosphate is a native nucleotide. The derivatives of GTP may be used as specific inhibitors against COVID-19[1].

  • CAS Number: 86-01-1
  • MF: C10H16N5O14P3
  • MW: 523.18000
  • Catalog: SARS-CoV
  • Density: 2.75g/cm3
  • Boiling Point: 1028.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 575.7ºC

Riddelline

Riddelline, a pyrrolizidine alkaloid, is a potent genotoxic agent. Riddelline induces significant elevations in unscheduled DNA synthesis and S-phase synthesis in rat liver[1].

  • CAS Number: 23246-96-0
  • MF: C18H23NO6
  • MW: 349.37800
  • Catalog: DNA/RNA Synthesis
  • Density: 1.34g/cm3
  • Boiling Point: 593.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 312.5ºC

Trovafloxacin Mesylate

Trovafloxacin mesylate is a broad-spectrum quinolone antibiotic with potent activity against Gram-positive, Gram-negative and anaerobic organisms. Trovafloxacin mesylate blocks the DNA gyrase and topoisomerase IV activity. Trovafloxacin mesylate is also a potent, selective and orally active pannexin 1 channel (PANX1) inhibitor with an IC50 of 4 μM for PANX1 inward current. Trovafloxacin mesylate does not inhibit connexin 43 gap junction or PANX2. Trovafloxacin mesylate leads to dysregulated fragmentation of apoptotic cells by inhibiting PANX1[1][2][3].

  • CAS Number: 147059-75-4
  • MF: C21H19F3N4O6S
  • MW: 512.45900
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: 630.5ºC at 760mmHg
  • Melting Point: >250 °C (dec.)
  • Flash Point: 335.1ºC

3’-O-Levulinyl-2’-deoxyadenosine

3’-O-Levulinyl-2’-deoxyadenosine 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: 440327-45-7
  • MF: C15H19N5O5
  • MW: 349.34
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 640.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 341.3±34.3 °C

5-Iodouridine

5-Iodouridine 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: 1024-99-3
  • MF: C9H11IN2O6
  • MW: 370.10
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 205-207ºC (dec.)(lit.)
  • Flash Point: N/A

EB 47, PARP-1 inhibitor

EB-47 dihydrochloride, a potent and selective PARP-1/ARTD-1 inhibitor with an IC50 value of 45 nM, shows modest potency against ARTD5 with an IC50 value of 410 nM. EB-47 mimics the substrate NAD+ and extends from the nicotinamide to the adenosine subsite[1].

  • CAS Number: 1190332-25-2
  • MF: C24H29Cl2N9O6
  • MW: 610.450
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC1-IN-4

HDAC1-IN-4 (JX34) is a potent Plasmodium falciparum HDAC1 inhibitor shows antimalarial activity (IC50 < 5 nM) and lower cytotoxicity[1].

  • CAS Number: 2482998-39-8
  • MF: C21H24BrClN6O2
  • MW: 507.81
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antitumor agent-68

Antitumor agent-68 is a potent tubulin inhibitor. Antitumor agent-68 shows potent anticancer activity with IC50s of 3.6 and 3.8 µM for HeLa and MCF-7 cells, respectively. Antitumor agent-68 exhibits good scavenging activity of ROS and DPPH radical in a dose-dependent manner[1].

  • CAS Number: 2566497-96-7
  • MF: C17H11NO2
  • MW: 261.27
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A