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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Membrane Transporter/Ion Channel >
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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 >
NF-κB IKK Keap1-Nrf2 MALT1
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Etoposide 4'-Phosphate

Etoposide phosphate (BMY-40481) is a potent anti-cancer chemotherapy agent and a selective topoisomerase II inhibitor to prevent re-ligation of DNA strands. Etoposide phosphate is the phosphate ester prodrug of etoposide and is considered as active equivalent to Etoposide. Etoposide phosphate induces cell cycle arrest, apoptosis, and autophagy[1][2].

  • CAS Number: 117091-64-2
  • MF: C29H33O16P
  • MW: 666.522
  • Catalog: Apoptosis
  • Density: 1.55 g/cm3
  • Boiling Point: 907.7±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 502.7±37.1 °C

8-Bromo-5’-O-(4-cyanobenzyl)-2’,3’-di-O-isopropylidene adenosine

8-Bromo-5’-O-(4-cyanobenzyl)-2’,3’-di-O-isopropylidene adenosine is an adenosine analog. Adenosine analogs mostly act as smooth muscle vasodilators and have also been shown to inhibit cancer progression. Its popular products are adenosine phosphate, Acadesine (HY-13417), Clofarabine (HY-A0005), Fludarabine phosphate (HY-B0028) and Vidarabine (HY-B0277)[1].

  • CAS Number: 1134156-53-8
  • MF: C21H21BrN6O4
  • MW: 501.33
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-Naphthohydroxamic acid

1-Naphthohydroxamic acid (Compound 2) is a potent and selective HDAC8 inhibitor with an IC50 of 14 μM. 1-Naphthohydroxamic acid is more selectively for HDAC8 than class I HDAC1 and class II HDAC6 (IC50 >100 μM). 1-Naphthohydroxamic acid does not increase global histone H4 acetylation and also does not reduce total intracellular HDAC activity[1][2].1-Naphthohydroxamic acid can induce tubulin acetylation[3].

  • CAS Number: 6953-61-3
  • MF: C11H9NO2
  • MW: 187.195
  • Catalog: HDAC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-TFA-ap-7-Deaza-ddA

7-TFA-ap-7-Deaza-ddA (compound 19c, US20060281100A1), a nucleotide derivative, can be used in the synthesis of thiotriphosphate nucleotide dye terminators which can be used in DNA sequencing reactions[1].

  • CAS Number: 114748-71-9
  • MF: C16H16F3N5O3
  • MW: 383.325
  • Catalog: DNA/RNA Synthesis
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 650.9±55.0 °C at 760 mmHg
  • Melting Point: 167-169 °C(Solv: ethyl ether (60-29-7))
  • Flash Point: 347.4±31.5 °C

N6-(3-Methoxybenzyl)-2’-C-methyl adenosine

N6-(3-Methoxybenzyl)-2’-C-methyl adenosine is an adenosine analog. Adenosine analogs mostly act as smooth muscle vasodilators and have also been shown to inhibit cancer progression. Its popular products are adenosine phosphate, Acadesine (HY-13417), Clofarabine (HY-A0005), Fludarabine phosphate (HY-B0028) and Vidarabine (HY-B0277)[1].

  • CAS Number: 2305415-85-2
  • MF: C19H23N5O5
  • MW: 401.42
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Keramamine A

Manzamine A, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A targets vacuolar ATPases and inhibits Autophagy in pancreatic cancer cells. Manzamine A has antimalarial and anticancer activities. Manzamine A also shows potent activity against HSV-1[1][2][3][4].

  • CAS Number: 104196-68-1
  • MF: C36H44N4O
  • MW: 548.76100
  • Catalog: HSV
  • Density: 1.26g/cm3
  • Boiling Point: 756.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 411.4ºC

3’-Deoxy-O6-methyl inosine

3’-Deoxy-O6-methyl inosine 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: 945215-53-2
  • MF: C11H14N4O4
  • MW: 266.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

9H-Purin-6-amine,N-methyl-9-b-D-xylofuranosyl

N6-Methyl-xylo-adenosine is an adenosine analog. Adenosine analogs mostly act as smooth muscle vasodilators and have also been shown to inhibit cancer progression. Its popular products are adenosine phosphate, Acadesine (HY-13417), Clofarabine (HY-A0005), Fludarabine phosphate (HY-B0028) and Vidarabine (HY-B0277)[1].

  • CAS Number: 65494-95-3
  • MF: C11H15N5O4
  • MW: 281.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.85g/cm3
  • Boiling Point: 649.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 346.3ºC

PF-06873600

PF-06873600 is a selective and orally bioavailable inhibitor of cyclin-dependent kinase (CDK), with Ki values of 0.09 nM, 0.13 nM and 0.16 nM for CDK2, CDK4 and CDK6, respectively. PF-06873600 has potential antineoplastic activity[1][2].

  • CAS Number: 2185857-97-8
  • MF: C20H27F2N5O4S
  • MW: 471.52
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S-(4-fluorophenyl) 4-fluorobenzenesulfonothioate

Tubulin inhibitor 29 (compound 3c) is a potent tubulin inhibitor with an IC50 value of 1.2 µM. Tubulin inhibitor 29 shows antiproliferative effects with an IC50 value of 7.5 µM for MCF-7 cells. Tubulin inhibitor 29 inhibits tubulin assembly and bounds in the colchicine site[1].

  • CAS Number: 2905-15-9
  • MF: C12H8F2O2S2
  • MW: 286.31800
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NEBULARINE

Nebularine 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: 550-33-4
  • MF: C10H12N4O4
  • MW: 252.23
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.91g/cm3
  • Boiling Point: 591.6ºC at 760mmHg
  • Melting Point: 181-182ºC
  • Flash Point: 311.6ºC

VEGFR-2-IN-22

VEGFR-2-IN-22 (Compound 25) is a dual VEGFR-2 and β-tubulin polymerization inhibitor with an IC50 of 19.82 nM against VEGFR-2. VEGFR-2-IN-22 induces apoptosis[1].

  • CAS Number: 2447587-73-5
  • MF: C26H24ClFN4O6
  • MW: 542.94
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ANI-7

A potent and selective (up to 263-fold) inhibitor of breast cancer cells with GI50 of 0.5 uM (MCF-7), via activation the aryl hydrocarbon receptor (AhR) pathway; inhibits other cell lines derived from other tumour types with GI50 of 3.2-46 uM (lung, colon, ovary, neuronal, glial, prostate, and pancreas); potently inhibits the growth of T47D, ZR-75-1, MCF-7, SKBR3, and MDA-MB-468 breast cancer cells with GI50 of 0.16-0.38 uM, induces cell cycle arrest checkpoint activation and DNA damage; binds to the AhR, induces translocation to the nucleus, activates the XRE, induces CYP1 activity, culminating in cell cycle arrest, checkpoint activation, DNA damage and cell death.

  • CAS Number: 931417-26-4
  • MF: C13H8Cl2N2
  • MW: 263.121
  • Catalog: Checkpoint Kinase (Chk)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Methylthienyl-carbonyl-JNJ-7706621

3-Methylthienyl-carbonyl-JNJ-7706621 is a potent and selective inhibitor of cyclin-dependent kinase (CDK), with IC50s of 6.4 nM and 2 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. 3-Methylthienyl-carbonyl-JNJ-7706621 also shows potent inhibition of GSK-3 (IC50=0.041 μM) and modest potency against CDK4, VEGF-R2, and FGF-R2 (IC50=0.11, 0.13, 0.22 μM, respectively). 3-Methylthienyl-carbonyl-JNJ-7706621 can be used for the research of cancer[1].

  • CAS Number: 443798-09-2
  • MF: C14H14N6O3S2
  • MW: 378.43
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DKFZ-748

DKFZ-748 is a selective HDAC10 inhibitor (pIC50=7.66), and shows anti-tumor activity[1].

  • CAS Number: 2490709-68-5
  • MF: C18H23N3O3
  • MW: 329.39
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Episilvestrol

Episilvestrol is a derivative of silvestrol, isolated from the fruits and twigs of Aglaia silvestris, and is a specific eIF4A-targeting translation inhibitor, with antitumor activity.

  • CAS Number: 697235-39-5
  • MF: C34H38O13
  • MW: 654.65800
  • Catalog: Eukaryotic Initiation Factor (eIF)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2'-O-MOE-A(Bz)-3'-phosphoramidite

DMT-2'-O-MOE-rA(Bz) phosphoramidite is an adenosine analog. Adenosine analogs mostly act as smooth muscle vasodilators and have also been shown to inhibit cancer progression. Its popular products are adenosine phosphate, Acadesine (HY-13417), Clofarabine (HY-A0005), Fludarabine phosphate (HY-B0028) and Vidarabine (HY-B0277)[1].

  • CAS Number: 251647-53-7
  • MF: C50H58N7O9P
  • MW: 932.0
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Ethyl-7,8-dihydro-8-oxo-9-(β-D-xylofuranosyl)guanine

7-Ethyl-7,8-dihydro-8-oxo-9-(β-D-xylofuranosyl)guanine 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: 2389988-43-4
  • MF: C12H17N5O6
  • MW: 327.29
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aurintricarboxylic acid

Aurintricarboxylic acid is a nanomolar-potency, allosteric antagonist with selectivity towards αβ-methylene-ATP-sensitive P2X1Rs and P2X3Rs, with IC50s of 8.6 nM and 72.9 nM for rP2X1R and rP2X3R, respectively[1]. Aurintricarboxylic acid is a potent anti-influenza agent by directly inhibiting the neuraminidase[2]. Aurintricarboxylic acid is an inhibitor of topoisomerase II and apoptosis[3]. Aurintricarboxylic acid is a selective inhibitor of the TWEAK-Fn14 signaling pathway[4].

  • CAS Number: 4431-00-9
  • MF: C22H14O9
  • MW: 422.341
  • Catalog: Influenza Virus
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 759.6±60.0 °C at 760 mmHg
  • Melting Point: 300 °C(lit.)
  • Flash Point: 427.1±29.4 °C

DNA gyrase B-IN-3

DNA gyrase B-IN-3 (Compound A) is a bacterial DNA gyrase B inhibitor (IC50: < 10 nM). DNA gyrase B-IN-3 has antibacterial activity against gram-positive strains[1].

  • CAS Number: 2412834-56-9
  • MF: C14H9Cl2N3O4S
  • MW: 386.21
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EC 144

EC144 is a potent and selective inhibitor of heat shock protein 90 (Hsp90) with an IC50 of 1.1 nM. EC144 inhibits tumor growth and causes partial tumor regressions. EC144 has the potential for the research of cancer diseases[1].

  • CAS Number: 911397-80-3
  • MF: C21H24ClN5O2
  • MW: 413.90100
  • Catalog: HSP
  • Density: 1.29±0.1 g/cm3(20 °C , 760mmHg)
  • Boiling Point: 674.1±65.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

N6-Bz-5'-O-DMTr-3'-deoxyadenosine-2'-O-CED-phosphoramidite

N6-Bz-5'-O-DMTr-3'-deoxyadenosine-2'-O-CED-phosphoramidite is an adenosine analog. Adenosine analogs mostly act as smooth muscle vasodilators and have also been shown to inhibit cancer progression. Its popular products are adenosine phosphate, Acadesine (HY-13417), Clofarabine (HY-A0005), Fludarabine phosphate (HY-B0028) and Vidarabine (HY-B0277)[1].

  • CAS Number: 207347-42-0
  • MF: C47H52N7O7P
  • MW: 857.93
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

m7GpppGmpG

m7GpppGmpG, an oligonucleotide, is an M7GpppNpG trinucleotide cap analogue. m7GpppGmpG can be used as a chemical tool enabling manufacturing of RNA featuring either cap 0 or cap 1 structures[1].

  • CAS Number: 1258049-00-1
  • MF: C32H43N15O25P4
  • MW: 1161.66
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cytidine-13C9,15N3

Cytidine-13C9,15N3 is the 13C and 15N labeled Cytidine[1]. Cytidine is a pyrimidine nucleoside and acts as a component of RNA. Cytidine is a precursor of uridine. Cytidine controls neuronal-glial glutamate cycling, affecting cerebral phospholipid metabolism, catecholamine synthesis, and mitochondrial function[2][3][4].

  • CAS Number: 202406-79-9
  • MF: 13C9H1315N3O5
  • MW: 255.13
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Crozbaciclib fumarate

Crozbaciclib fumarate is a CDK4/6 inhibitor with IC50s of 3 and 1 nM, respectively.

  • CAS Number: 2567494-39-5
  • MF: C32H34F2N6O4
  • MW: 604.65
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2(1H)-Pyrimidinone, 1-b-D-arabinofuranosyl-4-(methylamino)

N4-Methylarabinocytidine 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: 13491-42-4
  • MF: C10H15N3O5
  • MW: 257.24
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ARRY-520 (R enantiomer)

ARRY-520 R enantiomer is the R-enantiomer of ARRY-520. ARRY-520 is a synthetic kinesin spindle protein (KSP) inhibitor with IC50 of 6 nM.

  • CAS Number: 885060-08-2
  • MF: C20H22F2N4O2S
  • MW: 420.47600
  • Catalog: Kinesin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

8-azidoadenosine

8-Azidoadenosine is an adenosine analog. Adenosine analogs mostly act as smooth muscle vasodilators and have also been shown to inhibit cancer progression. Its popular products are adenosine phosphate, Acadesine (HY-13417), Clofarabine (HY-A0005), Fludarabine phosphate (HY-B0028) and Vidarabine (HY-B0277)[1].

  • CAS Number: 4372-67-2
  • MF: C10H12N8O4
  • MW: 308.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >200ºC (dec.)
  • Flash Point: N/A

XY028-133

XY028-133 (example 14) is a PROTAC-based CDK4/6 degrader with anti-tumor activity, extracted from patent WO2018106870A1[1].

  • CAS Number: 2229974-73-4
  • MF: C53H67N11O7S
  • MW: 1002.23
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Datelliptium chloride

Datelliptium chloride is a DNA-intercalating agent derived from ellipticine, with anti-tumor activities.

  • CAS Number: 105118-14-7
  • MF: C23H28ClN3O
  • MW: 397.94100
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A