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 >
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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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4-Amino-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-7H-pyrrolo[2.3-d]pyrimidine

2’-Deoxy-2’-fluoro-arabino-tubercidine 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: 169516-61-4
  • MF: C11H13FN4O3
  • MW: 268.24
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 603.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 318.5±31.5 °C

5-Benzylamino carbonyl-3’-O-acetyl-2’-O-methyl-5’-O-DMTr-uridine

5-Benzylamino carbonyl-3’-O-acetyl-2’-O-methyl-5’-O-DMTr-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: 2095417-22-2
  • MF: C41H41N3O10
  • MW: 735.8
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cevipabulin fumarate

Cevipabulin fumarate (TTI-237 fumarate) is a microtubule-active, oral active antitumor compound and inhibits the binding of [3H] vinblastine to tubulin, with an IC50 of 18-40 nM for cytotoxicity in human tumor cell line[1][2].

  • CAS Number: 849550-67-0
  • MF: C22H22ClF5N6O5
  • MW: 580.89200
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

eIF4A3-IN-10

eIF4A3-IN-10 (compound 58) is a silvestrol (HY-13251) analogue. eIF4A3-IN-10 interferes the assembling of eIF4F translation complex with EC50s of 35 and 100 nM for myc-LUC and the growth inhibition for MBA-MB-231 cells. eIF4A3-IN-10 can be used for the research of human cancer pathogenesis[1].

  • CAS Number: 1402931-72-9
  • MF: C29H29NO8
  • MW: 519.54
  • Catalog: Eukaryotic Initiation Factor (eIF)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mps1-IN-1 dihydrochloride

Mps1-IN-1 dihydrochloride is a potent, selective and ATP-competitive Mps1 kinase inhibitor, with an IC50 and a Kd of 367 nM and 27 nM[1].

  • CAS Number: 1883548-93-3
  • MF: C28H35Cl2N5O4S
  • MW: 608.58
  • Catalog: Mps1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3’-Deoxy-3’-flluoro-3-deazauridine

3’-Deoxy-3’-flluoro-3-deazauridine 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: 2072145-34-5
  • MF: C10H12FNO5
  • MW: 245.20
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2’-Deoxy-N3-methylcytidine hydriodide

2’-Deoxy-N3-methylcytidine hydriodide 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: 79043-77-9
  • MF: C10H16IN3O4
  • MW: 369.16
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OSIP-486823

OSIP-486823 is a novel microtubule-interfering agent with distinct biological effects on both protein kinase G (PKG) and microtubules.

  • CAS Number: 200803-37-8
  • MF: C29H28FNO4
  • MW: 473.535
  • Catalog: Microtubule/Tubulin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 667.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.4±31.5 °C

Alatrofloxacin

Alatrofloxacin, the parenteral prodrug of Trovafloxacin, is a fluoronaphthyridone which contains an L-alanyl-L-alanyl salt. Alatrofloxacin functions similar to other fluoroquinolone antibiotics in that it not only has antibiotic activity to kill invading organisms by interfering with DNA synthesis, it possesses immunosuppressive activity[1].

  • CAS Number: 146961-76-4
  • MF: C26H25F3N6O5
  • MW: 558.509
  • Catalog: DNA/RNA Synthesis
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 863.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 475.8±34.3 °C

Methotrexate α-tert-butyl ester

Methotrexate α-tert-butyl ester, capped by OtBu, significantly reduces tumor growth in HT1080 tumor bearing mice. Methotrexate is an antimetabolite and antifolate agent and is also an immunosuppressant and antineoplastic agent[1][2][3][4].

  • CAS Number: 79640-70-3
  • MF: C24H30N8O5
  • MW: 510.54600
  • Catalog: Antifolate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD 7762 hydrochloride

AZD-7762 hydrochloride is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with an IC50 of 5 nM for Chk1.

  • CAS Number: 1246094-78-9
  • MF: C17H20ClFN4O2S
  • MW: 398.88
  • Catalog: Checkpoint Kinase (Chk)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-(2-Deoxy-β-D-erythro-pentofuranosyl)-4(1H)-pyrimidinone

1-(2-Deoxy-β-D-erythro-pentofuranosyl)-4(1H)-pyrimidinone 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: 37109-98-1
  • MF: C9H12N2O4
  • MW: 212.20
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Folinic acid (Calcium)

Leucovorin Calcium is a reduced folic acid.IC50 Value: 30 μM for zcSHMT and70 μM for zmSHMT [2]Target: Antifolatein vitro: Increasing concentrations of leucovorin (N5-CHO-THF) inhibit both zcSHMT and hcSHMT activities substantially, yet to a lesser extent than zmSHMT. The IC50 of leucovorin is approximately 30 μM for zcSHMT and higher than 70 μM for zmSHMT. The differential inhibition is evident with the presence of 10 μM leucovorin, the concentration estimated in serum in a high-dose leucovorin rescue regimen [2].in vivo: Following intravenous administration, peak plasma concentrations of (6R) LV, (6S) LV, and 5-CH3 THF were 148 +/- 32, 59.1 +/- 22, and 17.8 +/- 17 microM, respectively. During oral administration of LV, virtually no (6S) LV appeared in the plasma. Steady-state plasma concentrations of (6R) LV and 5-CH3 THF were approximately 1.5 +/- 0.23 and 2.8 +/- 0.41 microM, respectively [1]. 24 fasted subjects were given 4 of a series of 5 single test doses between 20 and 100 mg, at 1-week intervals, of 5-formyl-THF as an oral solution of leucovorin calcium. Six separate subjects received 200 mg iv and po in a 2-way crossover. Blood and urine samples were collected over 24 hours for differential microbiological folate assays using Lactobacillus casei and Streptococcus faecalis. Using L casei activity to measure total serum folates, the area under the concentration-time curve from 0 to infinite time (AUC[0-infinity]) was calculated. Relative bioavailabilities were 78%, 62%, 49%, and 42% for the 40-, 60-, 80-, and 100-mg doses, respectively [3].Clinical trial: Leucovorin and Fluorouracil With or Without SU-5416 in Treating Patients With Metastatic Colorectal Cancer . Phase 3

  • CAS Number: 1492-18-8
  • MF: C20H21CaN7O7
  • MW: 511.501
  • Catalog: Antifolate
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 240-250ºC
  • Flash Point: N/A

DHODH-IN-7

DHODH-IN-7 is a human dihydroorotate dehydrogenase (DHODH) inhibitor, with an IC50 of 0.91 μM. DHODH-IN-7 induces differentiation in acute myeloid leukemia[1].

  • CAS Number: 2029049-77-0
  • MF: C21H21F3N2O2
  • MW: 390.40
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PTG-0861

PTG-0861 (JG-265) is a novel potent, selective HDAC6 inhibitor with IC50 of 5.92 nM, >36-fold selectivity over other HDACs.PTG-0861 (JG-265) displays HDAC6 cellular target engagement with EC50 of 0.59 uM (ELISA), has in vitro and cellular selectivity superior to HDAC6-selective inhibitor citarinostat (ACY-241).PTG-0861 (JG-265) demonstrates potency against several blood cancer cell lines (e.g. MV4-11, MM1S), whilst showing limited cytotoxicity against non-malignant cells and CD-1 mice.PTG-0861 (JG-265) exihibits promising in vitro pharmacokinetics achieved with good safety profile in cells and in vivo.

  • CAS Number: 2494082-34-5
  • MF: C15H9F5N2O3
  • MW: 360.24
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sodium 2-propylpentanoate

Valproic acid sodium salt is an anticonvulsants used to treat epilepsy, bipolar disorder and migraines. Valproic acid inhibits histone deacetylase 1 (HDAC1) with an IC50 of 0.4 mM.

  • CAS Number: 1069-66-5
  • MF: C8H15NaO2
  • MW: 166.193
  • Catalog: Autophagy
  • Density: 1.0803 g/cm3
  • Boiling Point: 220ºC at 760 mmHg
  • Melting Point: 300 °C
  • Flash Point: STABILITY

N3-Methyl-5-methyluridine

N3-Methyl-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: 3650-91-7
  • MF: C11H16N2O6
  • MW: 272.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bis-ANS dipotassium

Bis-ANS dipotassium is a fluorescent probe of hydrophobic protein. Bis-ANS binds to tubulin with a Kd of 2 μM[1]. Bis-ANS dipotassium is a potent biphasic modulator of protein liquid-liquid phase separation (LLPS). Bis-ANS dipotassium promotes LLPS at low concentrations but suppresses LLPS at high concentrations[2].

  • CAS Number: 65664-81-5
  • MF: C32H22K2N2O6S2
  • MW: 672.85300
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ombrabulin hydrochloride

Ombrabulin hydrochloride is a derivative of CA-4 phosphate, which is known to exhibit antivascular effects through selective disruption of the tubulin cytoskeleton of endothelial cells.

  • CAS Number: 253426-24-3
  • MF: C21H27ClN2O6
  • MW: 438.90200
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lomustine

Lomustine is a DNA alkylating agent, with antitumor activity.

  • CAS Number: 13010-47-4
  • MF: C9H16ClN3O2
  • MW: 233.695
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 88-90
  • Flash Point: N/A

3’-beta-C-Methylcytidine

3’-beta-C-Methylcytidine is a cytidine nucleoside analog. Cytidine analogs have a mechanism of inhibiting DNA methyltransferases (such as Zebularine, HY-13420), and have potential anti-metabolic and anti-tumor activities[1].

  • CAS Number: 20724-72-5
  • MF: C10H15N3O5
  • MW: 257.24
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

P276-00

Riviciclib hydrochloride (P276-00) is a potent CDK9-cyclinT1, CDK4-cyclin D1, CDK1-cyclinB, CDK2-cyclin A, CDK2-cyclin E, CDK6-cyclin D3, and CDK9-cyclin H inhibitor with IC50 values of 20 nM, 63 nM, 79 nM, 224 nM, 2500 nM, 396 nM, 2900 nM, respectively[1].Riviciclib hydrochloride shows antitumor activity on cisplatin-resistant cells[3].

  • CAS Number: 920113-03-7
  • MF: C21H21Cl2NO5
  • MW: 438.30
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AT-1727

Bimolane (AT-1727), a human topoisomerase II inhibitor, can be used as an anti-neoplastic agent and for the research of psoriasis. Bimolane shows leukemogenic activity and induces multiple types of chromosomal aberrations in human lymphocytes[1][2].

  • CAS Number: 74550-97-3
  • MF: C20H32N6O6
  • MW: 452.50
  • Catalog: Topoisomerase
  • Density: 1.326g/cm3
  • Boiling Point: 679.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 364.6ºC

KU-0060648

KU-0060648 is a dual inhibitor of PI3K and DNA-PK with IC50s of 4 nM, 0.5 nM, 0.1 nM, 0.594 nM and 8.6 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ and DNA-PK, respectively[1].

  • CAS Number: 881375-00-4
  • MF: C33H34N4O4S
  • MW: 582.713
  • Catalog: DNA-PK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 819.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 449.7±34.3 °C

Dolastatin 15

Dolastatin 15 (DLS 15), a depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent Dolastatin 10. Dolastatin 15 induces cell cycle arrest and apoptosis in multiple myeloma cells. Dolastatin 15 can be used as an ADC cytotoxin[1][2][3].

  • CAS Number: 123884-00-4
  • MF: C45H68N6O9
  • MW: 837.05600
  • Catalog: ADC Cytotoxin
  • Density: 1.2g/cm3
  • Boiling Point: 943.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 524.2ºC

N1-Allylpseudouridine

N1-Allylpseudouridine 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: 1613530-15-6
  • MF: C12H16N2O6
  • MW: 284.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(3-(Imidazo[2,1-b]thiazol-6-yl)phenyl)-2-methoxybenzamide

Sirtuin modulator 2 (Compound 132) is a sirtuin modulator with an ED50 equal or less than 50 μM[1].

  • CAS Number: 667910-69-2
  • MF: C19H15N3O2S
  • MW: 349.41
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ascamycin

Ascamycin is a 5'-O-sulfonamide ribonucleoside antibiotic produced by Streptomyces sp. JCM9888. Ascamycin has a selective antibacterial activity against Xanthomonas species with MIC values of 0.4 μg/mL, 12.5 μg/mL and 12.5 μg/mL for Xanthomonas citri, Xanthomonas oryzae and Mycobacterium phlei, respectively[1][2][3].

  • CAS Number: 91432-48-3
  • MF: C13H18ClN7O7S
  • MW: 451.84300
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

B I09

B I09 is an IRE-1 RNase inhibitor, with an IC50 of 1230 nM.

  • CAS Number: 1607803-67-7
  • MF: C16H17NO5
  • MW: 303.31
  • Catalog: IRE1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m7GpppAmpG

m7GpppAmpG is a trinucleotide cap analog with the capping efficiencies for the obtained RNAs of 90%[1].

  • CAS Number: 62858-30-4
  • MF: C32H43N15O24P4
  • MW: 1145.66
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A