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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N1-(1,1,1-Trifluoroethyl)pseudouridine

N1-(1,1,1-Trifluoroethyl)pseudouridine 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: 1613529-80-8
  • MF: C11H13F3N2O6
  • MW: 326.23
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-2'-Fd4C

L-2'-Fd4C, is an l-nucleoside analogue. L-2'-Fd4C has anti-human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activity[1].

  • CAS Number: 221662-50-6
  • MF: C9H10FN3O3
  • MW: 227.19
  • Catalog: HBV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PLK1-IN-7

PLK1-IN-7 (compound 30e) is a potent PLK1 inhibitor, with an IC50 of 0.66 nM. PLK1-IN-7 exhibits antiproliferative and antitumor activities[1].

  • CAS Number: 2938910-96-2
  • MF: C24H24F4N8O2
  • MW: 532.49
  • Catalog: Polo-like Kinase (PLK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

XPW1

XPW1 is a potent and selective CDK9 inhibitor with excellent activity against clear cell renal cell carcinoma (ccRCC) and low toxicity[1].

  • CAS Number: 2700286-66-2
  • MF: C36H39ClFN7O2
  • MW: 656.19
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

7-n-Propyl-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: 2389988-44-5
  • MF: C13H19N5O6
  • MW: 341.32
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DMTr-LNA-U-3-CED-Phosphora

DMTr-LNA-U-3-CED-phosphora is a phosphorite monomer that can be used in the synthesis of oligonucleotides.

  • CAS Number: 206055-76-7
  • MF:
  • MW:
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cimpuciclib

Cimpuciclib is a cyclin-dependent kinase(CDK) inhibitor and antineoplastic[1].

  • CAS Number: 2202767-78-8
  • MF: C30H35FN8O
  • MW: 542.65
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubulin polymerization-IN-22

Tubulin polymerization-IN-22 is a tubulin polymerization inhibitor with an IC50 of 8.1 μM. Tubulin polymerization-IN-22 arrests cell cycle at G2/M phase and induces apoptosis[1].

  • CAS Number: 2493052-22-3
  • MF: C19H16O4
  • MW: 308.33
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(4-(4-(3-Methyl-1H-pyrazol-5-ylamino)-6-(4-Methylpiperazin-1-yl)pyrimidin-2-ylthio)phenyl)propionamide

VE-465 is an Aurora kinase inhibitor. VE-465 induces cancer cell apoptosis. VE-465 has anticancer effects in multiple tumor models[1][2].

  • CAS Number: 639089-73-9
  • MF: C22H28N8OS
  • MW: 452.576
  • Catalog: Aurora Kinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3’-Azido-3’-deoxy-5-fluoro-beta-L-cytidine

3’-Azido-3’-deoxy-5-fluoro-beta-L-cytidine 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: 2095417-76-6
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BOLD-100

BOLD-100 is a ruthenium-based anticancer agent. BOLD-100 also is an inhibitor of stress-induced GRP78 upregulation, disrupting endoplasmic reticulum (ER) homeostasis and inducing ER stress and unfolded protein response (UPR). BOLD-100 interferes with the complex interplay between ER-stress response, lysosome dynamics, and autophagy execution[1].

  • CAS Number: 783324-98-1
  • MF: C14H12Cl4N4Ru
  • MW: 479.15
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S26948

S26948 is a specific peroxisome proliferator-activated receptor γ (PPARγ) modulator (EC50=8.83 nM) with potent antidiabetes and antiatherogenic effects. S26948 is a specific high-affinity agonist for PPARγ[1].

  • CAS Number: 353280-43-0
  • MF: C28H25NO7S
  • MW: 519.56600
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

McMMAF

Mc-MMAF is a protective group-conjugated MMAF. MMAF is a more potent drug than Monomethyl auristatin E (MMAE), but is charged and relatively membrane-impermeable, is a potent tubulin inhibitor, is a toxin payload in antibody drug conjugate.Target:MMAF is a new auristatin derivative with a charged C-terminal phenylalanine that attenuates its cytotoxic activity compared to its uncharged counterpart, Monomethyl auristatin E (MMAE). Because of MMAF is highly toxic, it cannot be used as a drug itself. MMAF induces potent antitumor effects when conjugated via protease cleavable linkers to a monoclonal antibody targeting internalizing, tumor-specific cell surface antigens. The linker to the monoclonal antibody is stable in extracellular fluid, but is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the anti-mitotic mechanism.

  • CAS Number: 863971-19-1
  • MF: C49H76N6O11
  • MW: 925.161
  • Catalog: Drug-Linker Conjugates for ADC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 1052.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 590.1±34.3 °C

G 5555

G-5555 is a potent p21-activated kinase 1 (PAK1) inhibitor with Kis of 3.7 nM and 11 nM for PAK1 and PAK2, respectively.

  • CAS Number: 1648863-90-4
  • MF: C25H25ClN6O3
  • MW: 492.957
  • Catalog: PAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 684.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 367.8±34.3 °C

CP-67015

CP-67015, a nalidixic acid analog, is a potent topoisomerase II inhibitor. CP-67015 is a positive direct-acting mutagen in mammalian cells with both gene and chromosomal level effects[1].

  • CAS Number: 100325-51-7
  • MF: C17H12F2N2O3
  • MW: 330.28600
  • Catalog: Topoisomerase
  • Density: 1.424g/cm3
  • Boiling Point: 496.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 254.2ºC

Tubulin polymerization-IN-25

Tubulin polymerization-IN-25 (compound 17f) is a dual inhibitor of tubulin polymerization and farnesyl transferase (FTase) with IC50s of 1.11 μM and 0.39 μM, respectively. Tubulin polymerization-IN-25 displays cytotoxicity and excellent antitumor activity [1].

  • CAS Number: 2490538-46-8
  • MF: C24H18N2O3S
  • MW: 414.48
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3’-O-MOE-U-2’-phosphoramidite

3’-O-MOE-U-2’-phosphoramidite 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: 1452849-90-9
  • MF: C42H53N4O10P
  • MW: 804.86
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LACTO-N-FUCOPENTAOSE I

Lacto-N-fucopentaose I (LNFPI) is a human milk oligosaccharide (HMO), possessing antiviral and antibacterial activity. Lacto-N-fucopentaose I can reduce capsid protein VP1 to block virus adsorption, promote CDK2 and reduce cyclin E to recover cell cycle S phase block. Lacto-N-fucopentaose I inhibits ROS production and apoptosis in virus-infected cells. Lacto-N-fucopentaose I can also regulate intestinal microbiota to affect immune system development[1].

  • CAS Number: 7578-25-8
  • MF: C32H55NO25
  • MW: 853.77100
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Geldanamycin

Geldanamycin is a Hsp90 inhibitor with antimicrobial activity against many Gram-positive and some Gram-negative bacteria.

  • CAS Number: 30562-34-6
  • MF: C29H40N2O9
  • MW: 560.636
  • Catalog: HSP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 783.9±60.0 °C at 760 mmHg
  • Melting Point: 255 °C
  • Flash Point: 427.9±32.9 °C

Gnetol

Gnetol is a phenolic compound isolated from the root of Gnetum ula Brongn. Gnetol potently inhibits COX-1 (IC50 of 0.78 μM) and HDAC. Gnetol is a potent tyrosinase inhibitor with an IC50 of 4.5 μM for murine tyrosinase and suppresses melanin biosynthesis. Gnetol has antioxidant, antiproliferative, anticancer and hepatoprotective activity. Gnetol also possesses concentration-dependent α-Amylase, α-glucosidase, and adipogenesis activities[1][2][3].

  • CAS Number: 86361-55-9
  • MF: C14H12O4
  • MW: 244.243
  • Catalog: HDAC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 540.8±30.0 °C at 760 mmHg
  • Melting Point: 87 - 90ºC
  • Flash Point: 269.7±19.2 °C

SIRT6-IN-1

SIRT2/6-IN-1 (Compound 5) is a SIRT6/SIRT2 inhibitor, with IC50s of 106 μM and 114 μM. SIRT2/6-IN-1 increases H3K9 acetylation, increases glucose uptake and reduces TNF-α secretion in cells[1].

  • CAS Number: 1214468-35-5
  • MF: C19H14N4O5S
  • MW: 410.40
  • Catalog: Sirtuin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cdc7-IN-18

Cdc7-IN-18 (compound 1-2) is a potent CDC7 inhibitor with an IC50 of 1.29 nM for Cdc7/DBF4 enzyme. Cdc7-IN-18 shows antiproliferative activities with IC50 of 53.62 nM in COLO205 cells[1].

  • CAS Number: 2562329-14-8
  • MF: C19H21N5OS
  • MW: 367.47
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3’-O-(2-Methoxyethyl)-5-methyluridine

3’-O-(2-Methoxyethyl)-5-methyluridine 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: 303197-29-7
  • MF: C13H20N2O7
  • MW: 316.31
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deoxyguanosine triphosphate trisodium salt

Deoxyguanosine triphosphate (dGTP) trisodium salt is a nucleotide precursor in cells for DNA synthesis. Deoxyguanosine triphosphate trisodium salt is used in reverse transcription-polymerase chain reaction (RT-PCR) for DNA amplification[1].

  • CAS Number: 93919-41-6
  • MF: C10H13N5Na3O13P3
  • MW: 573.127
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZDLD13

ZDLD13, a β-carboline, is an orally active and selective CDK4/CycD3 inhibitor with an IC50 value of 0.38 μM. ZDLD13 exhibits potent anti-HCT116 activity including inhibition of colony formation, inhibition of invasion and migration, inducing of apoptosis, and arresting of G1 phase in cell cycle. ZDLD13 shows significant tumor growth inhibition in HCT116 tumor xenograft model[1].

  • CAS Number: 2762278-95-3
  • MF: C18H14N4O
  • MW: 302.33
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubulin inhibitor 33

Tubulin inhibitor 33, a tubulin polymerization inhibitor, inhibits tubulin polymerization in a dose-dependent manner with an IC50 of 9.05 μM. Tubulin inhibitor 33 has antitumor effects and induces cell apoptosis that can be used for antitumor research[1].

  • CAS Number: 2944462-67-1
  • MF: C24H22N4O3
  • MW: 414.46
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CLK inhibitor 2

A potent, selective inhibitor of cdc2-like kinase CLK1 and CLK2 with IC50 of 1.1 and 2.4 nM, respectively; moderately inhibits PI3Kα, and >100-fold selectivity over SRPK1/2/3; inhibits phospho-SRSF4 in MDA-MB-468 cells, induces alternative splicing of the S6K pre-mRNA at 1.1-3.3 uM, exhibits growth inhibitory activity with GI50 of 3.0 uM, through splicing alterations in genes involved in growth and survival.

  • CAS Number: 1005776-20-4
  • MF: C20H20N6O
  • MW: 360.421
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCT 241533 dihydrochloride

CCT241533 dihydrochloride is a potent and selective ATP competitive inhibitor of CHK2 with an IC50 of 3 nM and Ki of 1.16 nM[1].

  • CAS Number: 1962925-28-5
  • MF: C23H29Cl2FN4O4
  • MW: 515.41
  • Catalog: Checkpoint Kinase (Chk)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ddTTP

ddTTP is one of 2',3'-dideoxyribonucleoside 5'-triphosphates (ddNTPs) that acts as chain-elongating inhibitor of DNA polymerase for DNA sequencing[1].

  • CAS Number: 611-60-9
  • MF: C10H17N2O13P3
  • MW: 466.16900
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KSP-IA

A potent, specific, allosteric and cell-active inhibitor of KSP with IC50 of 11 nM; has no ihibitory activity toward other kinesins, includin CENP-E, MKLP-1, KIF-3A, and uKHC (IC50>50 uM); induces the formation of monoastral spindles, causes mitotic arrest in a dose-dependent manner (EC50=30 nM) in A2780 ovarian carcinoma cells; sustained KSP inhibition activates the proapoptotic protein, Bax, and both activation of the spindle checkpoint and subsequent mitotic slippage are required for Bax activation.

  • CAS Number: 639074-49-0
  • MF: C21H22F2N2O
  • MW: 356.417
  • Catalog: Kinesin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A