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 >
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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
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 >
NF-κB IKK Keap1-Nrf2 MALT1
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VD/VDR
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CDK4/6-IN-6

CDK4/6-IN-6 (example A94) is a potent CDK4/CDK6 inhibitor with a Ki of 0.6 nM and 13.9 nM for CDK4/Cyclin D1 and CDK6/Cyclin D3, respectively[1].

  • CAS Number: 2380321-51-5
  • MF: C22H27ClFN5O3
  • MW: 463.93
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP1-IN-11

PARP1-IN-11 (compound 49) is a potent PARP1 inhibitor with IC50 value of 0.082 µM. PARP1-IN-11 shows complete inhibition of PARP2 and substantially inhibits PARP3, TNKS1 and TNKS2[1].

  • CAS Number: 2482484-87-5
  • MF: C16H12N2O4
  • MW: 296.28
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

vanicoside B

Vanicoside B is a phenylpropanoyl sucrose derivative, can be isolated from the herb Persicaria dissitiflora. Vanicoside B targets cyclin-dependent kinase 8 (CDK8) and exhibits anti-tumor activity. The potential mechanism is Vanicoside B blocks CDK8-mediated signaling pathways and decreases the expression of epithelial-mesenchymal transition proteins, so that it leads to cell cycle arrest and apoptosis[1][2].

  • CAS Number: 155179-21-8
  • MF: C49H48O20
  • MW: 956.893
  • Catalog: CDK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 1165.0±65.0 °C at 760 mmHg
  • Melting Point: 157-159 °C
  • Flash Point: 339.6±27.8 °C

Poloxin

Poloxin is a non-ATP competitive Polo-like Kinase 1 (PLK1) inhibitor that targets the polo-box domain, with an IC50 of appr 4.8 μM.

  • CAS Number: 321688-88-4
  • MF: C18H19NO3
  • MW: 297.34800
  • Catalog: Polo-like Kinase (PLK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Melflufen hydrochloride

Melflufen (Melphalan flufenamide) hydrochloride, a dipeptide prodrug of Melphalan, is an alkylating agent. Melflufen hydrochloride shows antitumor activity against multiple myeloma (MM) cells and inhibits angiogenesis. Melflufen hydrochloride induces irreversible DNA damage and cytotoxicity in MM cells[1][2].

  • CAS Number: 380449-54-7
  • MF: C24H31Cl3FN3O3
  • MW: 534.88
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4’-Methyl-5-methyluridine

4’-Methyl-5-methyluridine 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: 152540-75-5
  • MF: C11H16N2O6
  • MW: 272.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2',3',5'-Tri-O-acetyl-2-thiouridine

2',3',5'-Tri-O-acetyl-2-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: 28542-31-6
  • MF: C15H18N2O8S
  • MW: 386.38
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Retinoic acid

Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM.

  • CAS Number: 302-79-4
  • MF: C20H28O2
  • MW: 300.435
  • Catalog: Caspase
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 462.8±14.0 °C at 760 mmHg
  • Melting Point: 179-184ºC
  • Flash Point: 350.6±11.0 °C

6-Chloro-2-iodo-9-(2’,3’,5’-tri-O-acetyl-β-D-ribofuranosyl)purine

6-Chloro-2-iodo-9-(2’,3’,5’-tri-O-acetyl-β-D-ribofuranosyl)purine 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: 5987-76-8
  • MF: C16H16ClIN4O7
  • MW: 538.68
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.98g/cm3
  • Boiling Point: 643.3ºC at 760 mmHg
  • Melting Point: 181-183ºC
  • Flash Point: 342.9ºC

E1231

E1231 (E-1231) is a small molecule SIRT1 activator with EC50 of 0.83 uM, interactes with recombinant human SIRT1 protein and deacetylated liver X receptor-alpha (LXRα); increases ATP-binding cassette transporter A1 (ABCA1) expression in RAW 264.7 cells dependent on SIRT1 and LXRα, promotes cholesterol efflux and inhibited lipid accumulation in RAW 264.7 cells via SIRT1 and ABCA1; decreases total cholesterol and triglyceride levels in both serum and the liver in golden hamster hyperlipidemia models.

  • CAS Number: 1031195-19-3
  • MF: C21H21N3O3
  • MW: 363.410
  • Catalog: Sirtuin
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 605.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 320.2±31.5 °C

Enocitabine

Enocitabine, a nucleoside analog, is a potent DNA replication inhibitor and a DNA chain terminator. Enocitabine can be used as an effective chemotherapeutic agent for the treatment of acute myelogenous leukaemia and lymphocytic leukaemias[1].

  • CAS Number: 55726-47-1
  • MF: C31H55N3O6
  • MW: 565.785
  • Catalog: CMV
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 141-142ºC
  • Flash Point: N/A

8-Chloro-arabinoadenosine

8-Chloro-arabinoadenosine 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: 769872-68-6
  • MF: C10H12ClN5O4
  • MW: 301.69
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Metoprine

Metoprine (BW 197U) is a potent histamine N-methyltransferase (HMT) inhibitor. Metoprine, a diaminopyrimidine derivative, can cross the blood-brain barrier and increase brain histamine levels by inhibiting HMT[1][2]. Metoprine is an antifolate and antitumor agent[3].

  • CAS Number: 7761-45-7
  • MF: C11H10Cl2N4
  • MW: 269.13000
  • Catalog: Antifolate
  • Density: 1.447g/cm3
  • Boiling Point: 483.7ºC at 760 mmHg
  • Melting Point: 275-276ºC
  • Flash Point: 246.3ºC

Levomefolic acid-13C5

Levomefolic acid-13C5 is the 13C labeled Levomefolic acid[1]. Levomefolic acid (5-MTHF) is an orally active, brain-penetrant natural active form of folic acid and is one of the most widely used folic acid food supplements[2][3].

  • CAS Number: 2687960-08-1
  • MF: C1513C5H25N7O6
  • MW: 464.42
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EFdA-TP

EFdA-TP is a potent nucleoside reverse transcriptase (RT) inhibitor. EFdA-TP inhibits RT-catalyzed DNA synthesis as an effective immediate or delayed chain terminator (ICT or DCT). EFdA-TP inhibits HIV-1 RT with multiple mechanisms[1].

  • CAS Number: 950913-56-1
  • MF: C12H15FN5O12P3
  • MW: 533.19
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T-705RTP

T-705RTP is a selective and GTP-competitive influenza virus RNA polymerase inhibitor with an IC50 of 0.14 μM and a Ki of 1.52 μM. T-705RTP is the active triphosphate metabolite of T-705 and has potent anti-influenza virus activity[1][2].

  • CAS Number: 740790-94-7
  • MF: C10H15FN3O15P3
  • MW: 529.16
  • Catalog: Influenza Virus
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HIV-1 inhibitor-43

HIV-1 inhibitor-43 (compound 12) is a potent HIV-1 inhibitor with an EC50 of 21.3 nM, 6.2 nM, < 0.7 nM and < 0.7 nM for Y188L, K103N-Y181C, K103N and Y181C, respectively. HIV-1 inhibitor-43 can reduce HIV-1 RNA and protein p24[1].

  • CAS Number: 2493426-43-8
  • MF: C24H21ClN2O4S
  • MW: 468.95
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LIMK1 inhibitor BMS-4

LIMK1 inhibitor BMS-4 is a LIM Kinase (LIMK) inhibitor targeting to LIMK1/2. LIMK1 inhibitor BMS-4 inhibits phosphorylation of cofilin, the LIMK substrate. However, LIMK1 inhibitor BMS-4 is noncytotoxic on A549 cells[1][2].

  • CAS Number: 905298-84-2
  • MF: C23H23N7O2S
  • MW: 461.53900
  • Catalog: LIM Kinase (LIMK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PERK-IN-4

PERK-IN-4 is a potent and selective PERK (protein kinase R (PKR)-like endoplasmic reticulum kinase) inhibitor with an IC 50 of 0.3 nM. PERK is activated in response to a variety of endoplasmic reticulum stresses implicated in numerous disease states[1].

  • CAS Number: 1337531-89-1
  • MF: C24H19F4N5O
  • MW: 469.434
  • Catalog: PERK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 710.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 383.7±32.9 °C

Ganetespib(STA-9090)

Ganetespib is a heat shock protein 90 (HSP90) inhibitor which exhibits potent cytotoxicity in a wide variety of hematological and solid tumor cell lines.

  • CAS Number: 888216-25-9
  • MF: C20H20N4O3
  • MW: 364.398
  • Catalog: HSP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 685.8±57.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 368.5±32.1 °C

SBE 13 hydrochloride

SBE13 Hydrochloride is a potent and selective Plk1 inhibitor, with an IC50 of 200 pM; SBE13 Hydrochloride poorly inhibits Plk2 (IC50>66 μM) or Plk3 (IC50=875 nM).

  • CAS Number: 1052532-15-6
  • MF: C24H28Cl2N2O4
  • MW: 479.396
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2'-fluoro-5-bromo-1-beta-D-arabinofuranosylcytosine

5-Bromo-2’-deoxy-2’-fluoro-beta-D-arabinocytidine 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: 69123-93-9
  • MF: C9H11BrFN3O4
  • MW: 324.10
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.21 g/cm3
  • Boiling Point: 513.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 264.3ºC

methyl 2-deoxy-3,5-di-o-p-toluoyl-d-*rib ofuranoside

Methyl 2-deoxy-3,5-di-O-toluoyl-D-ribofuranoside 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: 4330-34-1
  • MF: C22H24O6
  • MW: 384.42
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 581.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 202.4±23.6 °C

SNX-2112(PF-04928473)

SNX-2112 is an orally active Hsp90 inhibitor, with a Kd of 16 nM for Hsp90 and IC50s of 30 nM, 30 nM for Hsp90 α and Hsp90 β, also induces Her-2 degradation, and inhibits Grp94 and Trap-1, with IC50s of 10 nM, 4.275 μM and 0.862 μM, respectively.

  • CAS Number: 908112-43-6
  • MF: C23H27F3N4O3
  • MW: 464.481
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 619.8±55.0 °C at 760 mmHg
  • Melting Point: 265-266℃
  • Flash Point: 328.6±31.5 °C

Methylnitronitrosoguanidine

Methylnitronitrosoguanidine (MNNG) is an alkylating agent with toxic and mutagenic effects[1].

  • CAS Number: 70-25-7
  • MF: C2H5N5O3
  • MW: 147.09
  • Catalog: DNA Alkylator/Crosslinker
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 207.8±23.0 °C at 760 mmHg
  • Melting Point: 118°C (dec.)
  • Flash Point: 79.5±22.6 °C

ATR-IN-24

ATR-IN-24 (Compound 1) is a ATR inhibitor. ATR-IN-24 has anticancer activity[1].

  • CAS Number: 2370889-43-1
  • MF: C23H26N6O2
  • MW: 418.49
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Hydroxymethyl xylouridine

5-Hydroxymethyl xylouridine 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: 52448-09-6
  • MF: C10H14N2O7
  • MW: 274.23
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2'-O-MOE-rC

2'-O-MOE-rC is a 2'-O-MOE modified nucleoside. 2'-O-MOE-rC can be used for synthesis of DNA[1][2].

  • CAS Number: 251647-54-8
  • MF: C48H56N5O9P
  • MW: 877.960
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-pyrimidine-2,4-dione

1-(β-D-Xylofuranosyl)-5-methyluracil 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: 52486-19-8
  • MF: C10H14N2O6
  • MW: 258.23
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.576g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2’-Bromo-2’-deoxy-5-methyluridine

2’-Bromo-2’-deoxy-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: 95585-76-5
  • MF: C10H13BrN2O5
  • MW: 321.12
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A