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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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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Intoplicine dimesylate

Intoplicine (RP 60475) dimesylate, an antitumor derivative in the 7H-benzo[e]pyrido[4,3-b]indole series, is a DNA topoisomerase I and II inhibitor. Intoplicine dimesylate strongly binds DNA (KA = 2 x 105 /M) and thereby increases the length of linear DNA[1][2].

  • CAS Number: 133711-99-6
  • MF: C23H32N4O7S2
  • MW: 540.65300
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pemetrexed-d5

Pemetrexed-d5 is the deuterium labeled Pemetrexed[1]. Pemetrexed (LY231514) is an antifolate, the Ki values of the pentaglutamate of Pemetrexed (LY231514) are 1.3, 7.2, and 65 nM for inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively[2].

  • CAS Number: 1129408-57-6
  • MF: C20H16D5N5O6
  • MW: 432.44
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RG7800

RG7800 a small molecule SMN2 splicing modifier to enter human clinical trials to treat spinal muscular atrophy.

  • CAS Number: 1449598-06-4
  • MF: C24H28N6O
  • MW: 416.5248
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ilaprazole sodium

Ilaprazole (IY-81149) sodium is an orally active proton pump inhibitor. Ilaprazole sodium irreversibly inhibits H+/K+-ATPase in a dose-dependent manner with an IC50 of 6 μM in rabbit parietal cell preparation. Ilaprazole sodium is used for the research of gastric ulcers. Ilaprazole sodium is also a potent TOPK (T-lymphokine-activated killer cell-originated protein kinase) inhibitor[1][2].

  • CAS Number: 172152-50-0
  • MF: C19H17N4NaO2S
  • MW: 388.419
  • Catalog: TOPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JPS014

JPS014 is a benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTAC). JPS014 degrades class I histone deacetylase (HDAC). JPS014 is potent HDAC1/2 degrader correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells[1].

  • CAS Number: 2669785-76-4
  • MF: C46H59N7O7S
  • MW: 854.07
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Xylosyltaxol

7-xylosyltaxol(Taxol-7-xyloside) is a taxol (Paclitaxel) derivative; Paclitaxel binds to tubulin and inhibits the disassembly of microtubules.IC50 Value:Target: Microtubule/TubulinPaclitaxel is a compound extracted from the Pacific yew tree with antineoplastic activity. Paclitaxel also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). Paclitaxel inhibits DNA synthesis and stimulates the release of tumor necrosis factor-α. Paclitaxel induces apoptosis in murine mammary carcinoma MCA-4 and ovarian carcinoma OCA-1 tumors.

  • CAS Number: 90332-66-4
  • MF: C52H59NO18
  • MW: 986.021
  • Catalog: Microtubule/Tubulin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 1062.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 596.3±34.3 °C

(R)​-​CR8

(R)​-​CR8 (CR8), a second-generation analog of Roscovitine, is a potent CDK1/2/5/7/9 inhibitor. (R)​-​CR8 (CR8) inhibits CDK1/cyclin B (IC50=0.09 μM), CDK2/cyclin A (0.072 μM), CDK2/cyclin E (0.041 μM), CDK5/p25 (0.11 μM), CDK7/cyclin H (1.1 μM), CDK9/cyclin T (0.18 μM) and CK1δ/ε (0.4 μM). (R)​-​CR8 (CR8) induces apoptosis and has neuroprotective effect[1][2].

  • CAS Number: 294646-77-8
  • MF: C24H29N7O
  • MW: 431.533
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 671.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 359.8±34.3 °C

HSP90-IN-13

HSP90-IN-13 (compound 5k) is a highly potent HSP90 pan inhibitor with an IC50 value of 25.07 nM. HSP90-IN-13 has multi-target activity against EGFR, VEGFR-2 and Topoisomerase-2. HSP90-IN-13 causes cell cycle arrest at G2/M phase and induces apoptosis of MCF-7 cells through mitochondrial-mediated pathway[1].

  • CAS Number: 2446055-29-2
  • MF: C26H21N5O3S
  • MW: 483.54
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DHODH-IN-15

DHODH-IN-15 (Compound 7b) is a hydroxyfurazan analog of A771726. DHODH-IN-15 is a dihydroorotate dehydrogenase (DHODH) inhibitor with an IC50 of 11 μM for rat liver DHODH. DHODH-IN-15 can be used for rheumatoid arthritis[1].

  • CAS Number: 1364791-88-7
  • MF: C15H11N3O3
  • MW: 281.27
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Arimoclomol

Arimoclomol (BRX-220 free base) is a co-inducer of heat shock proteins (HSP).

  • CAS Number: 289893-25-0
  • MF: C14H20ClN3O3
  • MW: 314.78800
  • Catalog: HSP
  • Density: 1.32g/cm3
  • Boiling Point: 539.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 279.9ºC

Uridine-d2

Uridine-d2 is the deuterium labeled Uridine[1].

  • CAS Number: 82740-98-5
  • MF: C9H10D2N2O6
  • MW: 246.21400
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Amino-5-cyano-1- (β-D-ribofuranosyl)-7H-pyrrolo[2,3-d] pyrimidine

4-Amino-5-cyano-1- (β-D-ribofuranosyl)-7H-pyrrolo[2,3-d] pyrimidine 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: 1704-25-2
  • MF: C12H13N5O4
  • MW: 291.26
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Busulfan

Busulfan is a potent alkylator, with chemotherapeutic activity.

  • CAS Number: 55-98-1
  • MF: C6H14O6S2
  • MW: 246.302
  • Catalog: DNA Alkylator/Crosslinker
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 464.0±28.0 °C at 760 mmHg
  • Melting Point: 114-117 °C(lit.)
  • Flash Point: 234.4±24.0 °C

Razoxane

Razoxane (ICRF 159) is an antiangiogenic topoisomerase II inhibitor, can be used for the research of renal cell carcinoma (RCC)[1].

  • CAS Number: 21416-67-1
  • MF: C11H16N4O4
  • MW: 268.26900
  • Catalog: Topoisomerase
  • Density: 1.333g/cm3
  • Boiling Point: 531.5ºC at 760mmHg
  • Melting Point: 193ºC
  • Flash Point: 275.3ºC

6-Thioguanine

6-Thioguanine is an anti-leukemia and immunosuppressant agent, acts as an inhibitor of SARS and MERS coronavirus papain-like proteases (PLpros) and also potently inhibits USP2 activity, with IC50s of 25 μM and 40 μM for Plpros and recombinant human USP2, respectively.

  • CAS Number: 154-42-7
  • MF: C5H5N5S
  • MW: 167.192
  • Catalog: SARS-CoV
  • Density: 2.1±0.1 g/cm3
  • Boiling Point: 460.7±37.0 °C at 760 mmHg
  • Melting Point: ≥300 °C(lit.)
  • Flash Point: 232.4±26.5 °C

palbociclib

Palbociclib (PD 0332991) is a selective CDK4 and CDK6 inhibitor with IC50s of 11 and 16 nM, respectively. Palbociclib is a drug for the treatment of ER-positive and HER2-negative breast cancer.

  • CAS Number: 571190-30-2
  • MF: C24H29N7O2
  • MW: 447.533
  • Catalog: CDK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 711.5±70.0 °C at 760 mmHg
  • Melting Point: 200ºC
  • Flash Point: 384.1±35.7 °C

1-(3’-O-[4,4’-Dimethoxytrityl]-alpha-L-threofuranosyl)-thymine

1-(3’-O-[4,4’-Dimethoxytrityl]-alpha-L-threofuranosyl)-thymine 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: 325683-89-4
  • MF: C30H30N2O7
  • MW: 530.57
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

USP1-IN-6

USP1-IN-6 (compound 11) is a USP1 inhibitor (IC50<50 nM). USP1-IN-5 also inhibits MDA-MB-436 cells with IC50 <50 nM[1].

  • CAS Number: 2925547-95-9
  • MF: C29H27F3N8O
  • MW: 560.57
  • Catalog: Deubiquitinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIRT1-IN-2

SIRT1-IN-2 (compound 3h) is a potent and selective SIRT1 (silent information regulator 1) inhibitor, with an IC50 of 1.6 μM[1].

  • CAS Number: 2470969-89-0
  • MF: C13H15ClN2O
  • MW: 250.72
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Amino-3,7-dihydro-5-iodo-7-β-D-ribofuranosyl-4H-pyrrolo[2,3-d]pyrimidin-4-one

2-Amino-3,7-dihydro-5-iodo-7-β-D-ribofuranosyl-4H-pyrrolo[2,3-d]pyrimidin-4-one 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: 444020-71-7
  • MF: C11H13IN4O5
  • MW: 408.15
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.6±0.1 g/cm3
  • Boiling Point: 723.5±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 391.4±35.7 °C

Synucleozid dihydrochloride

Synucleozid (NSC 377363) is a potent inhibitor of the SNCA mRNA that encodes α-synuclein protein (IC50=1.5 μM). Synucleozid selectively targets the α-synuclein mRNA 5′ UTR at the designed IRE site, decreases the amount of SNCA mRNA loaded into polysomes and thereby inhibits SNCA translation. Synucleozid has the potential for the investigation of Parkinson’s disease[1].

  • CAS Number: 502139-01-7
  • MF: C22H20N6
  • MW: 368.43
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Berzosertib (VE-822)

Berzosertib (VE-822) is an ATR inhibitor with a Ki value of less than 0.2 nM. It also inhibits ATM with a Ki of 34 nM.

  • CAS Number: 1232416-25-9
  • MF: C24H25N5O3S
  • MW: 463.552
  • Catalog: ATM/ATR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 674.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 361.7±31.5 °C

STAMBP-IN-1

STAMBP-IN-1 is a small-molecule inhibitor of STAMBP deubiquitinase, and interrupts STAMBP-Ub-NALP7 interaction. STAMBP-IN-1 decreases protein level of its inflammasome substrate NALP7 and suppresses IL-1b release after Toll-like receptor (TLR) agonism. STAMBP-IN-1 inhibits the activity of STAMBP to cleave recombinant di-Ub with an IC50 value of 0.33 mM[1].

  • CAS Number: 896683-78-6
  • MF: C27H28N4O4S
  • MW: 504.6
  • Catalog: Deubiquitinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Guanosine, 3'-O-methyl-

3'-O-Methylguanosine is a methylated nucleoside analogs and a RNA chain terminator. 3'-O-methylguanosine can inhibit early virus-specific RNA synthesis[1].

  • CAS Number: 10300-27-3
  • MF: C11H15N5O5
  • MW: 297.26700
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.98g/cm3
  • Boiling Point: 711.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 384.2ºC

Glabrone

Glabrone is an isoflavone isolated from Glycyrrhiza glabra roots. Glabrone exhibits anti-influenza activity and significant PPAR-γ ligand-binding activity[1][2].

  • CAS Number: 60008-02-8
  • MF: C20H16O5
  • MW: 336.33800
  • Catalog: PPAR
  • Density: 1.368g/cm3
  • Boiling Point: 554.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 202.6ºC

5-Propargylamino-ddCTP

5-Propargylamino-ddCTP, a nucleoside molecule that can be used to synthesis of cyanine dye-nucleotide conjugate which is used in nucleic acid labeling or sequence analysis[1].

  • CAS Number: 114748-56-0
  • MF: C12H19N4O12P3
  • MW: 504.22000
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubulin inhibitor 24

Tubulin inhibitor 24 is a potent tubulin inhibitor. Tubulin inhibitor 24 inhibits tubulin polymerization. Tubulin inhibitor 24 induces cell cycle arrest at the G2/M phase in a concentration-dependent manner. Tubulin inhibitor 24 shows antitumor activity with no obvious toxicity[1].

  • CAS Number: 2415761-65-6
  • MF: C22H21N3O3
  • MW: 375.42
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nimustine HCL

Nimustine hydrochloride (ACNU) is a DNA cross-linking and DNA alkylating agent, which induces DNA replication blocking lesions and DNA double-strand breaks and inhibits DNA synthesis, commonly used in chemotherapy for glioblastomas[1][2][3].

  • CAS Number: 55661-38-6
  • MF: C9H14Cl2N6O2
  • MW: 309.152
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 186 °C
  • Flash Point: N/A

CDK-IN-10

CDK-IN-10 (example 54) is a cyclin dependent kinase (CDK) inhibitor that can be used in cancer research[1].

  • CAS Number: 660822-84-4
  • MF: C18H18N4O2
  • MW: 322.36
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MI-192 HCl

MI-192 is a selective HDAC2 and HDAC3 inhibitor with IC50s of 30 nM and 16 nM, respectively. MI-192 is more selective for HDAC2/3 than other HDAC isomers.MI-192 induces myeloid leukaemic cells apoptosis. Anticaner and neuroprotective activities[1][2].

  • CAS Number: 1415340-63-4
  • MF: C24H21N3O2
  • MW: 383.44
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 565.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 295.5±30.1 °C