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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Apoptosis >
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Autophagy >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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2-Pentanone, 5-phenyl

Phenylbutyrate is a potent histone deacetylases (HDACs) inhibitor. Phenylbutyrate can be used for urea cycle disorder research[1][2].

  • CAS Number: 2235-83-8
  • MF: C11H14O
  • MW: 162.22800
  • Catalog: HDAC
  • Density: 0.96g/cm3
  • Boiling Point: 261.2ºC at 760mmHg
  • Melting Point: 106-107 °C
  • Flash Point: 121.5ºC

HSP70/SIRT2-IN-2

HSP70/SIRT2-IN-2 (Compounds 1a) is a dual inhibitor for SIRT2 and HSP70, with IC50 of 45.1±5.0 μM for SIRT2. HSP70/SIRT2-IN-2 has antitumor activity[1].

  • CAS Number: 1796557-72-6
  • MF: C17H13N3S3
  • MW: 355.50
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ispinesib

Ispinesib is a specific inhibitor of KSP, with a Ki app of 1.7 nM.

  • CAS Number: 336113-53-2
  • MF: C30H33ClN4O2
  • MW: 517.062
  • Catalog: Kinesin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 708.0±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.0±35.7 °C

eIF4A3-IN-7

eIF4A3-IN-7 is a potent inhibitor of eIF4A3. eIF4A3-IN-7 has the potential for researching cancer and other dysproliferative diseases (extracted from patent WO2019161345A1, Compound 8)[1].

  • CAS Number: 2374759-82-5
  • MF: C26H25NO7
  • MW: 463.48
  • Catalog: Eukaryotic Initiation Factor (eIF)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Uridine,4-thio-, 2',3',5'-tribenzoate (6CI,7CI,8CI,9CI)

2’,3’,5’-Tri-O-benzoyl-4-thiouridine 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: 15049-50-0
  • MF: C30H24N2O8S
  • MW: 572.59
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.45g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vinorelbine (ditartrate)

Vinorelbine (ditartrate) is an anti-mitotic agent which inhibits the proliferation of Hela cells with IC50 of 1.25 nM.

  • CAS Number: 125317-39-7
  • MF: C53H66N4O20
  • MW: 1079.106
  • Catalog: Autophagy
  • Density: 1.36g/cm3
  • Boiling Point: N/A
  • Melting Point: 181-183°C
  • Flash Point: N/A

Setrobuvir

Setrobuvir (ANA598) is an orally active non-nucleosidic HCV NS5B polymerase inhibitor. ANA-598 inhibits both de novo RNA synthesis and primer extension, with IC50s between 4 and 5 nM. Setrobuvir also shows excellent binding affinity to SARS-CoV-2 RdRp and induces RdRp inhibition[1][2].

  • CAS Number: 1071517-39-9
  • MF: C25H25FN4O6S2
  • MW: 560.61800
  • Catalog: HCV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sovilnesib

Sovilnesib is a kinesin-like protein KIF18A inhibitor (WO2020132648). Sovilnesib can be used for the research of cancer[1].

  • CAS Number: 2410796-79-9
  • MF: C26H34F2N6O4S
  • MW: 564.65
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

9-(3-Deoxy-3-fluoro-β-D-ribofuranosyl)-6-(5-phenylpyridin-3-yl)purine

9-(3-Deoxy-3-fluoro-β-D-ribofuranosyl)-6-(5-phenylpyridin-3-yl)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: 1612191-96-4
  • MF: C21H18FN5O3
  • MW: 407.4
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC 687852

b-AP15 is a specific inhibitor of the deubiquitinating enzymes UCHL5 and Usp14.

  • CAS Number: 1009817-63-3
  • MF: C22H17N3O6
  • MW: 419.387
  • Catalog: Deubiquitinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 670.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 359.3±31.5 °C

RSS0680

RSS0680 (Example 22) is a bifunctional compound targeted protein degradation of kinases. RSS0680 degrades AAK1, CDK1, CDK16, CDK2, CDK4, CDK6, EIF2AK4, GAK, LATSl, LIMK2, MAPK6, MAPKAPK5, MARK2, MARK4, MKNK2, NEK9, RPS6KB1, SIK2, SNRK, STK17A, STK17B, STK35, and WEEl. RSS0680 can be used for research of disease or disorder mediated by aberrant kinase activity[1].

  • CAS Number: 2769753-48-0
  • MF: C52H64N10O6S3
  • MW: 1021.32
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BChE/HDAC6-IN-2

BChE/HDAC6-IN-2 (compound 29a) is a dual inhibitor of BChE and HDAC6 with IC50s of 1.8 nM and 71.0 nM, respectively. BChE/HDAC6-IN-2 has prominently neuroprotective effects and reactive oxygen species (ROS) scavenging activity. BChE/HDAC6-IN-2 is also an effective chelator of metal ion (Fe2+ and Cu2+). BChE/HDAC6-IN-2 inhibits phosphorylation of tau, and exhibits moderate immunomodulatory effect.

  • CAS Number: 2925457-33-4
  • MF: C27H30N4O4
  • MW: 474.55
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Semustine

Semustine is a DNA alkylator, binds to DNA, and acts as a cancer chemotherapeutic agent[1].

  • CAS Number: 13909-09-6
  • MF: C10H18ClN3O2
  • MW: 247.72200
  • Catalog: DNA Alkylator/Crosslinker
  • Density: 1.31 g/cm3
  • Boiling Point: N/A
  • Melting Point: 64°C (rough estimate)
  • Flash Point: N/A

Aloisine A

Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC50s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC50=0.5 µM) and GSK-3β (IC50=1.5 µM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research[1][2].

  • CAS Number: 496864-16-5
  • MF: C16H17N3O
  • MW: 267.32600
  • Catalog: CDK
  • Density: 1.227g/cm3
  • Boiling Point: N/A
  • Melting Point: 281-283ºC
  • Flash Point: N/A

MK-5108(VX-689)

MK-5108 is a highly potent and specific inhibitor of Aurora-A kinase with an IC50 value of 0.064 nM.

  • CAS Number: 1010085-13-8
  • MF: C22H21ClFN3O3S
  • MW: 461.937
  • Catalog: Aurora Kinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 637.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 339.4±34.3 °C

3,3'-Diethyl-9-methylthiacarbocyanine iodide

3,3'-Diethyl-9-methylthiacarbocyanine iodide is a cyanine dye, also a tau aggregation inhibitor, with an IC50 value of 0.28 μM for tau. 3,3'-Diethyl-9-methylthiacarbocyanine iodide can cause misfunction of the microtubule cytoskeleton. 3,3'-Diethyl-9-methylthiacarbocyanine iodide can be used for researching Alzheimer’s disease[1].

  • CAS Number: 3065-79-0
  • MF: C22H23IN2S2
  • MW: 506.46600
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 290ºC(dec.)(lit.)
  • Flash Point: N/A

Ethynylcytidine

Ethynylcytidine is a new nucleoside antimetabolite.

  • CAS Number: 180300-43-0
  • MF: C11H13N3O5
  • MW: 267.23800
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.61g/cm3
  • Boiling Point: 536.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.2ºC

CDK7-IN-7

CDK7-IN-7 is a potent and selective CDK7 kinase inhibitor with an IC50 of <50 nM (Patent CN112661745A, compound T-01)[1].

  • CAS Number: 2640208-01-9
  • MF: C20H20BrF3N6O2
  • MW: 513.31
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ON 108600

ON 108600 is a inhibitor for CK2 (Casein Kinase2)/TNIK/DYRK1 , with the IC50s for DYRK1A/DYRKB, DYRK2, CK2α1/CK2α2, and TNIK of 0.016 μm/0.007 μM, 0.028 μM, 0.05 μM/0.005 μM, and 0.005 μM, respectively. ON 108600 has antitumor activity[1].

  • CAS Number: 1585246-23-6
  • MF: C22H14Cl2N2O6S2
  • MW: 537.39
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N4-Benzoyl-5-methylcytidine

N4-Benzoyl-5-methylcytidine 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: 160107-15-3
  • MF: C17H19N3O6
  • MW: 361.35
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Methoxybenzamide

3-Methoxybenzamide (3-MBA), an inhibitor of ADP-ribosyltransferase (ADPRTs) and PARP, inhibits cell division in Bacillus subtilis, leading to filamentation and eventually lysis of cells[1]. 3-Methoxybenzamide (3-MBA) enhances in vitro plant growth, microtuberization, and transformation efficiency of blue potato (Solanum tuberosum L. subsp. andigenum)[2].

  • CAS Number: 5813-86-5
  • MF: C8H9NO2
  • MW: 151.163
  • Catalog: PARP
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 280.0±23.0 °C at 760 mmHg
  • Melting Point: 132.5-135.5 °C(lit.)
  • Flash Point: 146.8±18.9 °C

2’-β-C-Methyl-6-azauridine

2’-β-C-Methyl-6-azauridine 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: 172605-95-7
  • MF: C9H13N3O6
  • MW: 259.22
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-(4-Thio-beta-D-ribofuranosyl)cytosine

4′-Thiocytidine 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: 93080-09-2
  • MF: C9H13N3O4S
  • MW: 259.28
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RHI002-Me

RHI002-Me is a RHI002 derivative, is a derivative hRNaseH2 inhibitor[1].

  • CAS Number: 314261-66-0
  • MF: C18H19N3O2S2
  • MW: 373.492
  • Catalog: DNA/RNA Synthesis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 562.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 294.1±30.1 °C

2-Hydrazinyl-adenosine

2-Hydrazinyl-adenosine 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: 15763-11-8
  • MF: C10H15N7O4
  • MW: 297.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.29±0.1 g/cm3(Predicted)
  • Boiling Point: 583.1±60.0 °C(Predicted)
  • Melting Point: 208-210ºC
  • Flash Point: N/A

IQTub4P

IQTub4P is a potent microtubule (MT) inhibitor. IQTub4P has the cytotoxicity in in HeLa cells, with EC50 of 170 nM. IQTub4P inhibits microtubule structure and function. IQTub4P is well-tolerated in vivo[1].

  • CAS Number: 2376321-67-2
  • MF: C19H18NNa2O8P
  • MW: 465.30
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6RK73

6RK73 is a covalent irreversible and specific UCHL1 inhibitor with an IC50 of 0.23 µM. 6RK73 shows almost no inhibition of UCHL3 (IC50=236 µM). 6RK73 specifically inhibit UCHL1 activity in breast cancer[1].

  • CAS Number: 1895050-66-4
  • MF: C13H17N5O2S
  • MW: 307.37
  • Catalog: Deubiquitinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SPC-180002

SPC-180002 is a SIRT1/3 dual inhibitor, with IC50 values of 1.13 and 5.41 μM, respectively. SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. SPC-180002 strongly inhibits cell cycle progression and cancer cell growth. SPC-180002 activates the Nrf2 signaling pathway[1].

  • CAS Number: 2170274-53-8
  • MF: C18H23NO4
  • MW: 317.38
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palmatine hydroxide

Palmatine hydroxide is an orally active and irreversible indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor with IC50s of 3 μM and 157μM against HEK 293-hIDO-1 and rhIDO-1, respectively. Palmatine hydroxide can also inhibit West Nile virus (WNV) NS2B-NS3 protease in an uncompetitive manner with an IC50 of 96 μM. Palmatine hydroxide shows anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, antibacterial, anti-viral activities[1][2][3][4][5].

  • CAS Number: 131-04-4
  • MF: C21H23NO5
  • MW: 369.41100
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 772077B dihydrochloride

SB-772077B dihydrochloride is an aminofurazan-based Rho kinase( ROCK) inhibitor with IC50s of 5.6 nM and 6 nM toward ROCK1 and ROCK2, respevtively[1].

  • CAS Number: 607373-46-6
  • MF: C15H20Cl2N8O2
  • MW: 415.28
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A