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.


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PLK1-IN-5

PLK1-IN-5 is a potent PLK1 inhibitor with an IC50 of < 500 nM. PLK1-IN-5 shows anticancer effects (WO2008113711A1; compound I-4)[1].

  • CAS Number: 1001343-34-5
  • MF: C28H39N7O3
  • MW: 521.65
  • Catalog: Polo-like Kinase (PLK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sirtuin-1 inhibitor 1

Sirtuin-1 inhibitor 1 (Compound 8) is an inhibitor of Sirtuin-1 that plays important roles in obesity-induced diabetes and aging-related diseases[1].

  • CAS Number: 945114-10-3
  • MF: C20H17N3O2
  • MW: 331.37
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5’-O-(4,4’-Dimethoxytrityl)-2’-O-(2-methoxyethyl) adenosine

5’-O-(4,4’-Dimethoxytrityl)-2’-O-(2-methoxyethyl) 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: 1384253-67-1
  • MF: C34H37N5O7
  • MW: 627.69
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

eIF4A3-IN-9

eIF4A3-IN-9 (compound 57) is a silvestrol (HY-13251) analogue. eIF4A3-IN-9 interferes the assembling of eIF4F translation complex with EC50s of 29, 450 and 80 nM for myc-LUC, tub-LUC and the growth inhibition for MBA-MB-231 cells. eIF4A3-IN-9 can be used for the research of human cancer pathogenesis[1].

  • CAS Number: 1402931-71-8
  • MF: C28H27NO8
  • MW: 505.52
  • Catalog: Eukaryotic Initiation Factor (eIF)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3,5-Bis-O-(2,4-dichlorobenzyl)guanosine

3,5-Bis-O-(2,4-dichlorobenzyl)guanosine is a guanosine analog. Some guanosine analogs have immunostimulatory activity. In some animal models, they also induce type I interferons, producing antiviral effects. Studies have shown that the functional activity of guanosine analogs is dependent on the activation of Toll-like receptor 7 (TLR7)[1].

  • CAS Number: 2095417-36-8
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3’-O-(2-Methoxyethyl)cytidine

3’-O-(2-Methoxyethyl)cytidine is a cytidine 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: 2305415-84-1
  • MF: C12H19N3O6
  • MW: 301.30
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2',3'-Didehydro-2',3'-dideoxyuridine

2',3'-Didehydro-2',3'-dideoxyuridine 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: 5974-93-6
  • MF: C9H10N2O4
  • MW: 210.19
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.448g/cm3
  • Boiling Point: 443.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 221.9ºC

p97-IN-1

p97-IN-1 is a potent p97 inhibitor with an IC50 <30 nM (WO2015109285A1, compound FF07)[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Uridine-5-oxyacetic acid

Uridine-5-oxyacetic acid 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: 28144-25-4
  • MF: C11H14N2O9
  • MW: 318.24
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrphostin 47

Tyrphostin AG213 (AG213) is an inhibitor of epidermal growth factor receptor (EGFR) protein tyrosine kinase (IC50=0.85 μM). Tyrphostin AG213 inhibits tyrosine kinase activity IC50=2.4 μM) and topoisomerase II (IC100=50 μM). Tyrphostin AG213 can induce nonapoptotic cell programmed death in tumor cells[1][2][3].

  • CAS Number: 122520-86-9
  • MF: C10H8N2O2S
  • MW: 220.248
  • Catalog: Topoisomerase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 474.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 240.8±31.5 °C

8-Benzyloxyadenosine

8-Benzyloxyadenosine 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: 131265-29-7
  • MF: C17H19N5O5
  • MW: 373.36
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T-2 TOXIN

T-2 Toxin (T-2 Mycotoxin) is a toxic trichothecene mycotoxin produced by various Fusarium species in feedstuffs and cereal grains, LD50 values of T-2 Toxin in mice and rats are 5.2 and 1.5 mg/kg BWa,respectively [1]. T-2 Toxin (T-2 Mycotoxin) can be transformed into a variety of metabolite, the typical metabolites of T-2 toxin in animals are HT-2 toxin and T-2-triol, which are hydrolysates[1]. T-2 Toxin (T-2 Mycotoxin) is an inhibitor of protein synthesis resulting from binding peptidyltransferase, which is an integral part of the 60s ribosomal subunit. T-2 Toxin (T-2 Mycotoxin) inhibits the synthesis of DNA and RNA, interferes with the metabolism of membrane phospholipids, and increases the level of liver lipid peroxides[1]. T-2 Toxin (T-2 Mycotoxin) induces apoptosis in the immune system, gastrointestinal tissues, and fetal tissues[2].

  • CAS Number: 21259-20-1
  • MF: C24H36O9
  • MW: 466.521
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 544.9±50.0 °C at 760 mmHg
  • Melting Point: 151.5℃
  • Flash Point: 177.0±23.6 °C

BS 181 2HCl

BS-181 dihydrochloride is a potent and selective CDK7 inhibitor (IC50=21 nM) than Seliciclib (HY-30237). BS-181 is also against CDK2, CDK5 and CDK9 with IC50 values of 880 nM, 3000 nM and 4200 nM, respectively (fails to block CDK1, 4 and 6). BS-181 dihydrochloride inhibits a panel of cancer cells growth (IC50=11.5 μM-37.3 μM) and induces cell apoptosis. BS-181 dihydrochloride has the potential for the research of cancer therapy[1][2].

  • CAS Number: 1883548-83-1
  • MF: C22H34Cl2N6
  • MW: 453.45
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CK2-IN-7

CK2-IN-7 (compound 2) is an inhibitor of casein kinase 2 (CK2). CK2-IN-7 shows synergistic effect with structurally distinct CK2 chemical probe: SGC-CK2-1, against cancer[1].

  • CAS Number: 2920559-18-6
  • MF: C19H14N4O2
  • MW: 330.34
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY3143921 hydrate

LY3143921 ((S)-Example 2) hydrate is an orally active CDC7 kinase inhibitor. LY3143921 hydrate shows broad in vitro anticancer activity[1].

  • CAS Number: 2733342-93-1
  • MF: C16H14FN5O2
  • MW: 327.31
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

eIF4A3-IN-5

eIF4A3-IN-5 is a potent inhibitor of eukaryotic initiation factor 4A (eIF4A), such as eIF4AI and eIF4AII. eIF4A3-IN-5 has the potential for the research of eIF4A dependent diseases, including the research of cancer (extracted from patent US20170145026A1)[1].

  • CAS Number: 2100145-31-9
  • MF: C26H22N2O7
  • MW: 474.46
  • Catalog: Eukaryotic Initiation Factor (eIF)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anticancer agent 48

Anticancer agent 48 (compound 48) is a broad spectrum anticancer agent. Anticancer agent 48 inhibits tubulin polymerization. Anticancer agent 48 shows antiproliferative activity. Anticancer agent 48 shows antitumor activity in vivo. Anticancer agent 48 has the potential for the research of solid and hematological tumors[1].

  • CAS Number: 2395009-13-7
  • MF: C26H25N3O4
  • MW: 443.49
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(4,4-2H2)Hexadecanoic acid

Palmitic acid-d2-4 is the deuterium labeled Palmitic acid. Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. PA can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells[1][2].

  • CAS Number: 30719-28-9
  • MF: C16H30D2O2
  • MW: 258.44
  • Catalog: HSP
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 340.6±5.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 154.1±12.5 °C

Rohinitib

Rohinitib is a potent and specific inhibitor of eIF4A1, inhibits growth and survival of AML cells especially cells with FLT3-ITD.

  • CAS Number: 1139253-73-8
  • MF: C29H31NO8
  • MW: 521.56
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7,8-Dihydro-8-oxo-7-propargyl-3’-deoxy-3’-fluoro guanosine

7,8-Dihydro-8-oxo-7-propargyl-3’-deoxy-3’-fluoro guanosine 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: 2389988-55-8
  • MF: C13H14FN5O5
  • MW: 339.28
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Silvestrol

Silvestrol is a eukaryotic translation initiation factor 4A (eIF4A) inhibitor isolated from the fruits and twigs of Aglaia foveolata.

  • CAS Number: 697235-38-4
  • MF: C34H38O13
  • MW: 654.658
  • Catalog: Eukaryotic Initiation Factor (eIF)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 800.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 252.4±27.8 °C

KX2-361

KX2-361 (KX-02) is a Src-kinase and tubulin polymerization inhibitor. KX2-361 shows good oral bioavailability and readily crosses the BBB in mice. KX2-361 shows anti-tumor activity and induces apoptosis of Glioblastoma (GBM) cell[1].

  • CAS Number: 897016-26-1
  • MF: C24H24FN3O2
  • MW: 405.46
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 660.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.0±31.5 °C

CUDC-907

Fimepinostat (CUDC-907) potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes with an IC50 of 19/54/39 nM and 1.7/5.0/1.8/2.8 nM for PI3Kα/PI3Kβ/PI3Kδ and HDAC1/HDAC2/HDAC3/HDAC10 , respectively.

  • CAS Number: 1339928-25-4
  • MF: C23H24N8O4S
  • MW: 508.553
  • Catalog: HDAC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Methylguanosine

N2-methylguanosine is a modified nucleoside that occurs at several specific locations in many tRNA's.

  • CAS Number: 2140-77-4
  • MF: C11H15N5O5
  • MW: 297.267
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.0±0.1 g/cm3
  • Boiling Point: 709.5ºC at 760mmHg
  • Melting Point: 233 °C (decomp)(Solv: water (7732-18-5))
  • Flash Point: 382.9ºC

MAO A/HSP90-IN-2

MAO A/HSP90-IN-2 (compound 4-C) is a dual inhibitor of HSP90and MAO A with the IC50 values of 0.016 and 4.58 μM, respectively. MAO A/HSP90-IN-2 increases HSP70 expression and reduces HER2 and phospho-Akt expression, and decreases IFN-γ induced PD-L1 expression in GL26 cells. MAO A/HSP90-IN-2 inhibits the growth of Temozolomide (HY-17364) -sensitive and -resistant GBM cells, colon cancer, leukemia, non-small cell lung and other cancers, and has potential to inhibit tumor immune escape[1].

  • CAS Number: 2927489-99-2
  • MF: C25H31ClN2O4
  • MW: 458.98
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M3814

M3814 is a potent and selective inhibitor of DNA-dependent Protein Kinase (DNA-PK).

  • CAS Number: 1637542-33-6
  • MF: C24H21ClFN5O3
  • MW: 481.91
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NVS-PAK1-1

NVS-PAK1-1 is a potent and selective allosteric PAK1 inhibitor with an IC50 of 5 nM.

  • CAS Number: 1783816-74-9
  • MF: C23H25ClF3N5O
  • MW: 479.93
  • Catalog: PAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

INO-1001

INO-1001 is a potent and selective Poly (ADP-ribose) polymerase (PARP) inhibitor with an IC50 of 0.05-1 μM. INO-1001 is a potent enhancer of radiation sensitivity and enhances radiation-induced cell killing by interfering with DNA repair mechanisms, resulting in necrotic cell death[1]. INO-1001 has anti-tumor effects[2].

  • CAS Number: 501364-82-5
  • MF: C23H25N3O4S
  • MW: 439.52700
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Pyrrolidinone,5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-1-[5-methoxy-2-nitro-4-[[tris(1-methylethyl)silyl]oxy]benzoyl]-,(5S)-

Tesirine intermediate-1 is the intermediate of Tesirine (HY-128952). Tesirine (SG3249), a pyrrole benzodiazepine (PBD) dimer, is a DNA small channel crosslinker with strong cytotoxicity. Tesirine can be used to synthesize Antibody-Drug Conjugates (ADCs), the warhead component of the payload is SG3199 (HY-101161), which has strong anticancer cell activity.

  • CAS Number: 1430738-05-8
  • MF: C28H48N2O7Si2
  • MW: 580.86
  • Catalog: DNA Alkylator/Crosslinker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMVC

BMVC is a potent G-quadruplex (G4) stabilizer and a selective telomerase inhibitor with an IC50 of ~0.2 μM. BMVC inhibits Taq DNA polymerase with an IC50 of ~2.5 μM. BMVC increases the melting temperature of G4 structure of telomere and accelerates telomere length shortening. Anticancer activities[1][2].

  • CAS Number: 627810-06-4
  • MF: C28H25I2N3
  • MW: 657.33
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A