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 >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
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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Metabolic Enzyme/Protease >
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
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
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Topoisomerase II inhibitor 3

Topoisomerase II inhibitor 3 (Compound 6 h ) is a acridone derivatives, as well as a Type II DNA topoisomerase (topo II) inhibitor , as a topo IIα/β inhibitor with the value of IC50 is 0.17 μM for topo IIα and the value of IC50 is 0.23 μM for topo IIβ subtypes, caused obvious DNA damage, and induced apoptosis by triggering the loss of mitochondrial membrane potential[1].

  • CAS Number: 99140-25-7
  • MF: C18H20N4O4
  • MW: 356.38
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DNA-PK-IN-10

DNA-PK-IN-10 is a DNA-PK inhibitor. DNA-PK-IN-10 can be used for the research of breast cancer and non-small cell lung cancer[1].

  • CAS Number: 2919315-89-0
  • MF: C25H28N6O2
  • MW: 444.53
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AK-7

AK-7 is a selective cell- and brain-permeable SIRT2 inhibitor, with an IC50 of 15.5 μM.

  • CAS Number: 420831-40-9
  • MF: C19H21BrN2O3S
  • MW: 437.351
  • Catalog: Sirtuin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

rubitecan

Rubitecan (RFS 2000), a camptothecin derivative, is an orally active topoisomerase I inhibitor with broad antitumor activity, and induces protein-linked DNA single-strand breaks, thereby blocking DNA and RNA synthesis in dividing cells[1][2][3].

  • CAS Number: 91421-42-0
  • MF: C20H15N3O6
  • MW: 393.350
  • Catalog: Topoisomerase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 816.3±65.0 °C at 760 mmHg
  • Melting Point: 182-186ºC
  • Flash Point: 447.5±34.3 °C

Nicotinamide riboside malate

Nicotinamide riboside malate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside malate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities[1]. Nicotinamide riboside malate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease[2].

  • CAS Number: 2415659-01-5
  • MF: C15H20N2O10
  • MW: 388.33
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Troglitazone-d4

Troglitazone-d4 is deuterium labeled Troglitazone. Troglitazone is a PPARγ agonist, with EC50s of 550 nM and 780 nM for human and murine PPARγ receptor, respectively.

  • CAS Number: 2749370-85-0
  • MF: C24H23D4NO5S
  • MW: 445.56
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vinflunine

Vinflunine is a new vinca alkaloid uniquely fluorinated with the properties of mitotic-arresting and tubulin-interacting activity.Target: Microtubule/TubulinThe major effects of Vinflunine on dynamic instability are a slowing of the microtubule growth rate, an increase in growth duration, and a reduction in shortening duration. The effects of Vinflunine on the readmilling rate is examined by following [3H]GTP incorporation into MAP-rich microtubules, and the IC50 is 0.42 μM [1]. Vinflunine induced mitotic accumulation with IC50 with 18.8 nM, which decreases the centromere dynamicity by 44% and increases the time centromeres spent ina paused state by 63% [2]. Treatment of Vinflunine induces a rapid change in endothelial cell shape: cells retracts and assumes a rounded morphology. Mean IC50 values are 9.9 × 10-5 M × 10-5 M for fibronectin and 5.0× 10-5 M × 10-5 M for type IV collagen. A short 4 hours exposure of endothelial cells to Vinflunine at 10-8 0.05). An ID50 value (dose which inhibits 50% of bFGF-induced neovascularisation) is calculated as 1 mg/kg. Low doses of Vinflunine reduce the number of experimental liver metastases by human LS174T colon cancer cell. A slight overall decrease in liver metastatic foci is already observed at the very low dose of 0.16 mg/kg Vinflunine, although maximal overall inhibition is reached at the maximal tolerated dose (MTD) of 20 mg/kg [3].

  • CAS Number: 162652-95-1
  • MF: C45H54F2N4O8
  • MW: 816.92900
  • Catalog: Microtubule/Tubulin
  • Density: 1.39 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Brefeldin A

Brefeldin A is a specific inhibitor of protein trafficking which blocks the protein transport from the endoplasmic reticulum to the Golgi complex.

  • CAS Number: 20350-15-6
  • MF: C16H24O4
  • MW: 280.359
  • Catalog: Autophagy
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 492.7±45.0 °C at 760 mmHg
  • Melting Point: 200-205ºC
  • Flash Point: 180.8±22.2 °C

Topoisomerase I inhibitor 6

Topoisomerase I inhibitor 6 (Compound 3) is a potent inhibitor of Topoisomerase I. Topoisomerase I inhibitor 6 is able to trap DNA-Top1 cleavage complex and found to be less cytotoxic in non-cancerous cell line. Topoisomerase I inhibitor 6 has the potential for the research of cancer diseases[1].

  • CAS Number: 2393082-56-7
  • MF: C23H21N7O
  • MW: 411.46
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-15

ATR-IN-15 (compound 1) is an orally active and potent ATR kinase inhibitor, with an IC50 of 8 nM. ATR-IN-15 also inhibits human colon tumor cells LoVo, DNA-PK and PI3K, with IC50 values of 47, 663 and 5131 nM, respectively[1].

  • CAS Number: 2756665-52-6
  • MF: C19H22N8O
  • MW: 378.43
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IPA-3

IPA-3 is a selective non-ATP competitive PAK1 inhibitor with IC50 of 2.5 μM, and shows no inhibition to group II PAKs (PAKs 4-6).

  • CAS Number: 42521-82-4
  • MF: C20H14O2S2
  • MW: 350.454
  • Catalog: PAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 543.7±35.0 °C at 760 mmHg
  • Melting Point: 172℃
  • Flash Point: 263.4±24.7 °C

Nalidixic Acid-d5

Nalidixic Acid-d5 is the deuterium labeled Nalidixic acid. Nalidixic acid, a quinolone antibiotic, is effective against both gram-positive and gram-negative bacteria. Nalidixic acid acts in a bacteriostatic manner in lower concentrations and is bactericidal in higher concentrations. Nalidixic acid inhibits a subunit of DNA gyrase and topoisomerase IV and reversibly blocks DNA replication in susceptible bacteria[1].

  • CAS Number: 1189467-36-4
  • MF: C12H12N2O3
  • MW: 232.23528
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 229-230°C
  • Flash Point: N/A

Sorivudine

Sorivudine (BV-araU) is an orally active synthetic pyrimidine nucleoside antimetabolite drug. Sorivudine derives its antiviral activity from selective conversion by a specific thymidine kinase present in certain DNA viruses to nucleotides, which can in turn interfere with viral DNA synthesis[1].

  • CAS Number: 77181-69-2
  • MF: C11H13BrN2O6
  • MW: 349.13500
  • Catalog: DNA/RNA Synthesis
  • Density: 1.979g/cm3
  • Boiling Point: N/A
  • Melting Point: 182 °C
  • Flash Point: N/A

SRT1720 HCl

SRT 1720 Hydrochloride is a selective activator of SIRT1 with an EC1.5 of 0.16 μM, and shows less potent activities on SIRT2 and SIRT3 with EC1.5s of 37 μM and 300 μM, respectively.

  • CAS Number: 1001645-58-4
  • MF: C25H23N7OS.xHCl
  • MW: 506.022
  • Catalog: Autophagy
  • Density: 1.58
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide

CHIC35, an analog of EX-527, is a potent and selective inhibitor of SIRT1 (IC50=0.124 µM). CHIC35 shows potential selective inhibition against SIRT1 over SIRT2 (IC50=2.8 µM) or SIRT3 (IC50>100 µM)[1]. CHIC35 has anti-inflammatory effects and can be used for CHARGE syndrome research[1][2].

  • CAS Number: 848193-72-6
  • MF: C14H15ClN2O
  • MW: 262.73500
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Me-CTP.4Li

5-Methylcytidine 5′-triphosphate (5-Methyl-CTP) is a modified nucleoside triphosphates. 5-Methylcytidine 5′-triphosphate can apply in replacing unmodified mRNA, resulting in the increase of translational properties and stability, as well as the reduction of innate immune responses in human and other mammalian cells[1].

  • CAS Number: 327174-86-7
  • MF: C10H18N3O14P3
  • MW: 497.182903
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gypenoside XLIX

Gypenoside XLIX, a dammarane-type glycoside, is a prominent component of G. pentaphyllum. Gypenoside XLIX is a selective peroxisome proliferator-activated receptor (PPAR)-alpha activator and inhibits cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) overexpression and hyperactivity in human endothelial cells[1].

  • CAS Number: 94987-08-3
  • MF: C52H86O21
  • MW: 1047.227
  • Catalog: PPAR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 1105.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 306.9±27.8 °C

N4-Benzoyl-2'-deoxy-5'-O-DMT-2'-fluoro-cytidine phosphoramidite

2'-F-Bz-dC Phosphoramidite can be used in the synthesis of oligoribonucleotides[1].

  • CAS Number: 161442-19-9
  • MF: C46H51FN5O8P
  • MW: 851.89800
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thymidine-13C-1

Thymidine-13C-1 is the 13C labeled Thymidine. Thymidine, a specific precursor of deoxyribonucleic acid, is used as a cell synchronizing agent. Thymidine is a DNA synthesis inhibitor that can arrest cell at G1/S boundary, prior to DNA replication[1]

  • CAS Number: 240407-53-8
  • MF: C10H14N2O5
  • MW: 243.22100
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mesalamine impurity P

Mesalamine impurity P is an impurity of Mesalamine (HY-15027). 5-Aminosalicylic acid (Mesalamine) acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB[1].

  • CAS Number: 887256-40-8
  • MF: C13H11NO6S
  • MW: 309.294
  • Catalog: PAK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

8-Benzyloxy-3’-deoxy-3’-fluoroguanosine

8-Benzyloxy-3’-deoxy-3’-fluoroguanosine 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: 2389988-61-6
  • MF: C17H18FN5O5
  • MW: 391.35
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Remdesivir

Remdesivir is a nucleoside analogue, with effective antiviral activity, with EC50s of 74 nM for ARS-CoV and MERS-CoV in HAE cells, and 30 nM for murine hepatitis virus in delayed brain tumor cells.

  • CAS Number: 1809249-37-3
  • MF: C27H35N6O8P
  • MW: 602.576
  • Catalog: SARS-CoV
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-mercaptopurine riboside

6-​Thioinosine (6TI) is a purine antimetabolite, acts as an anti-adipogenesis agent, downregulates mRNA levels of PPAR γ and C/EBPα, as well as PPAR γ target protein such as LPL, CD36, aP2, and LXRα[1][2].

  • CAS Number: 574-25-4
  • MF: C10H12N4O4S
  • MW: 284.29200
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.02g/cm3
  • Boiling Point: 714.7ºC at 760mmHg
  • Melting Point: 220-223ºC(lit.)
  • Flash Point: 386ºC

NMS-1286937

NMS-1286937 is a potent, selective and orally available PLK1 inhibitor, with an IC50 of 2 nM.

  • CAS Number: 1034616-18-6
  • MF: C24H27F3N8O3
  • MW: 532.518
  • Catalog: Polo-like Kinase (PLK)
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 757.8±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 412.1±35.7 °C

N-Trityl-morpholino-T-5'-O-phosphoramidite

N-Trityl-morpholino-T-5'-O-phosphoramidite is a phosphorite monomer that can be used in the synthesis of oligonucleotides.

  • CAS Number: 2434654-73-4
  • MF: C38H46N5O5P
  • MW: 683.78
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DENV-IN-5

DENV-IN-5 (Compound 4b) is a dengue virus (DENV) inhibitor with EC50s of 1.47, 9.23, 7.08 and 8.91 μM against DENV-I ∼ IV replication, respectively. DENV-IN-5 also inhibits HIV-1IIIB strain with an EC50 of 0.1512 μM[1].

  • CAS Number: 2375781-06-7
  • MF: C23H25ClF2N4OS
  • MW: 478.99
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMA-37

AMA-37, an Arylmorpholine analog, is ATP-competitive DNA-PK inhibitor, with IC50 values of 0.27 μM (DNA-PK), 32 μM (p110α), 3.7 μM (p110β), and 22 μM (p110γ), respectively[1][2].

  • CAS Number: 404009-46-7
  • MF: C17H17NO3
  • MW: 283.32200
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Alaninechlamydocin

1-Alaninechlamydocin, a cyclic tetrapeptide, is a potent HDAC inhibitor (IC50=6.4 nM). 1-Alaninechlamydocin induces G2/M cell cycle arrest and apoptosis in MIA PaCa-2 cells[1].

  • CAS Number: 141446-96-0
  • MF: C27H36N4O6
  • MW: 512.598
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 871.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 481.1±34.3 °C

3’-Deoxy-3’-α-C-methyl-N6,N6-dimethyladenosine

3’-Deoxy-3’-α-C-methyl-N6,N6-dimethyladenosine 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: 2095417-44-8
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Adenosine, 2-methyl-

2-Methyladenosine is an adenosine analogue. Adenosine analogs mostly act as smooth muscle vasodilators and have also been shown to inhibit cancer progression. The popular products in this series are adenosine phosphate, Acadesine (HY-13417), Clofarabine (HY-A0005), Fludarabine phosphate (HY-B0028) and Vidarabine (HY-B0277)[1].

  • CAS Number: 16526-56-0
  • MF: C11H15N5O4
  • MW: 281.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.96g/cm3
  • Boiling Point: 517.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 266.9ºC