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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AS2863619

AS2863619 enables conversion of antigen-specific effector/memory T cells into Foxp3+ regulatory T (Treg) cells for the treatment of various immunological diseases. AS2863619 is a potent, orally active cyclin-dependent kinase 8 (CDK8) and CDK19 inhibitor with IC50s of 0.61 nM and 4.28 nM, respectively. STAT5 activation enhanced by AS2863619 inhibition of CDK8/19, which consequently activates the Foxp3 gene[1].

  • CAS Number: 2241300-51-4
  • MF: C16H14Cl2N8O
  • MW: 405.24
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tamoxifen-d5

Tamoxifen-d5 (ICI 47699-d5) is a deuterium labeled Tamoxifen. Tamoxifen (ICI 47699) is a selective estrogen receptor modulator (SERM). Tamoxifen is a potent Hsp90 activator and enhances the Hsp90 molecular chaperone ATPase activity[1][2].

  • CAS Number: 157698-32-3
  • MF: C26H24D5NO
  • MW: 376.54500
  • Catalog: Apoptosis
  • Density: 1.057g/cm3
  • Boiling Point: 482.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 140ºC

SNX-0723

SNX-0723 is a selective, brain-permeable, orally acitve small-molecule inhibitor of Hsp90 (IC50=14 nM) that inhibits alpha-synuclein oligomerization with EC50 of 48 nM; induces Hsp70 (IC50=31 nM), and decreases expression of several known Hsp90 client proteins:HER2 (IC50=9.4 nM), ribosomal protein s6 (pS6) (IC50=13 nM), and PERK (IC50=5.5 nM); shows significant brain concentrations along with induction of brain Hsp70 in vivo with promising PK properties.

  • CAS Number: 1073969-18-2
  • MF: C22H26FN3O3
  • MW: 399.47
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MEK/PI3K-IN-1

MEK/PI3K-IN-1 (compound 6r) is a potent MEK/PI3K inhibitor, with IC50 values of 124 nM (MEK1), 130 nM (PI3Kα), and 236 nM (PI3Kδ), respectively. MEK/PI3K-IN-1 suppresses pAKT and pERK1/2 levels. MEK/PI3K-IN-1 shows anti-proliferative activity against tumor cell lines[1].

  • CAS Number: 2281803-28-7
  • MF: C36H37F5IN9O6
  • MW: 913.63
  • Catalog: PERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Emetine hydrochloride

Emetine hydrochloride, derived from the ipecac root, is a potent anti-protozoal and emetic agent. Emetine hydrochloride inhibits viral polymerases and inhibits Zika and Ebola virus infections. Emetine hydrochloride potently inhibits autophagy and has anti-malarial, anti-bacterial and anti-amoebic effect[1][2][3][4].

  • CAS Number: 14198-59-5
  • MF: C29H41ClN2O4
  • MW: 517.100
  • Catalog: Bacterial
  • Density: 1.17g/cm3
  • Boiling Point: 624.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 331.7ºC

2-Chloro-2’-β-C-methyl-6-N,N-dimethyladenosine

2-Chloro-2’-β-C-methyl-6-N,N-dimethyladenosine 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: 2095417-43-7
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

P 22077

P 22077 is a cell-permeable ubiquitin-specific protease 7 (USP7) inhibitor with an EC50 of 8.01 μM. It also inhibits USP47 with an EC50 of 8.74 μM.

  • CAS Number: 1247819-59-5
  • MF: C12H7F2NO3S2
  • MW: 315.31600
  • Catalog: Deubiquitinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Uramustine

Uramustine is an oral alkylating agent, effective in the treatment of lymphosarcoma, chronic lymphatic leukaemia, and thrombocythemia.

  • CAS Number: 66-75-1
  • MF: C8H11Cl2N3O2
  • MW: 252.098
  • Catalog: Influenza Virus
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 206°C (rough estimate)
  • Flash Point: N/A

MMAF sodium

MMAF sodium (Monomethylauristatin F sodium) is an antitubulin agent that inhibit cell division; attenuates its cytotoxic activity compared to MMAE. MMAF sodium is widely used as a cytotoxic component of antibody-drug conjugates (ADCs) to treat several different cancer types.

  • CAS Number: 1799706-65-2
  • MF: C39H64N5NaO8
  • MW: 753.94
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2’-Fluoro-2’-deoxy-ara-C(Bz)-3’-phosphoramidite

2’-Fluoro-2’-deoxy-ara-C(Bz)-3’-phosphoramidite 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: 1404463-12-2
  • MF: C46H51FN5O8P
  • MW: 851.9
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-O-Benzoyl-1,2,3-tri-O-acetyl-4-C-methyl-D-ribofuranose

5-O-Benzoyl-1,2,3-tri-O-acetyl-4-C-methyl-D-ribofuranose 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: 503543-44-0
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ceramides Mixture

Ceramides Mixture is an endogenous ceramide and consists of hydroxy and non-hydroxy fatty acid-containing ceramides. Ceramides Mixture is a main lipid component of the permeability barrier in epidermis. Ceramides Mixture is involved in the regulation of growth inhibition, cell cycle arrest, and modulation of telomerase activity[1][2].

  • CAS Number: 100403-19-8
  • MF: C24H47NO3
  • MW: 397.63488
  • Catalog: Telomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

USP25 and 28 inhibitor AZ-1

USP25/28 inhibitor AZ1 (AZ1) is a potent, selective, noncompetitive, dual ubiquitin specific protease (USP) 25/28 inhibitor with IC50s of 0.7 μM and 0.6 μM, respectively. USP25/28 inhibitor AZ1 reduces cell viability across a range of cancer cell lines[1].

  • CAS Number: 2165322-94-9
  • MF: C17H16BrF4NO2
  • MW: 422.21
  • Catalog: Deubiquitinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Amino-4-deoxy-10-methylpteroic acid

Methotrexate metabolite (DAMPA), the active metabolite of Methotrexate. Methotrexate is a folic acid antagonist that is widely used as an immunosuppressant and chemotherapeutic agent[1].

  • CAS Number: 19741-14-1
  • MF: C15H15N7O2
  • MW: 325.325
  • Catalog: Antifolate
  • Density: 1.532
  • Boiling Point: 689.3±65.0 °C at 760 mmHg
  • Melting Point: 242 ºC
  • Flash Point: 370.7±34.3 °C

PI3K/AKT-IN-2

PI3K/AKT-IN-2 (Compound 12c) is a PI3K and AKT inhibitor. PI3K/AKT-IN-2 blocks the epithelial-mesenchymal transition (EMT) and induces apoptosis. PI3K/AKT-IN-2 inhibits the polymerization of tubulin[1].

  • CAS Number: 2684412-41-5
  • MF: C32H27BrO10
  • MW: 651.45
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

C527

C527 is a is a pan DUB enzyme inhibitor, with a high potency for the USP1/UAF1 complex (IC50=0.88 μM).

  • CAS Number: 192718-06-2
  • MF: C17H8FNO3
  • MW: 293.249
  • Catalog: Deubiquitinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 488.6±47.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 249.3±29.3 °C

Bendamustine-d8 hydrochloride

Bendamustine-d8 (hydrochloride) is deuterium labeled Bendamustine (hydrochloride). Bendamustine hydrochloride (SDX-105), a purine analogue, is a DNA cross-linking agent. Bendamustine hydrochloride activats DNA-damage stress response and apoptosis. Bendamustine hydrochloride has potent alkylating, anticancer and antimetabolite properties[1].

  • CAS Number: 1185068-23-8
  • MF: C16H14D8Cl3N3O2
  • MW: 402.77
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T326

A potent and selective HDAC3 inhibitor with IC50 of 0.26 uM, with no activity against HDAC1/4/6/8; induces dose-dependent selective increase of NF-κB acetylation in human colon cancer HCT116 cells, induces growth inhibition of cancer cells, and activates HIV gene expression in latent HIV-infected cells; shows promising activity for anticancer and antiviral benefits.

  • CAS Number: 1451042-19-5
  • MF: C21H18N6O3S
  • MW: 434.474
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sodium 4-Phenylbutyrate-d11

Phenylbutyrate-d11 (sodium) is deuterium labeled Sodium 4-phenylbutyrate. Sodium 4-phenylbutyrate (4-PBA sodium) is an inhibitor of HDAC and endoplasmic reticulum (ER) stress, used in cancer and infection research[1].

  • CAS Number: 1392208-11-5
  • MF: C10D11NaO2
  • MW: 197.25
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDK4/6-IN-17

CDK4/6-IN-17 (compound 12) is an orally active CDK4/6 inhibitor with IC50 ranging of 10-100 nM in BE(2) cells. CDK4/6-IN-17 inhibits tumor growth in COLO205 xenograft model[1].

  • CAS Number: 2035069-96-4
  • MF: C27H28F4N8
  • MW: 540.56
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thailanstatin D

Thailanstatin D, an analogue of Thailanstatin A, is able to inhibit AR-V7 gene splicing by interfering the interaction between U2AF65 and SAP155 and preventing them from binding to polypyrimidine tract located between the branch point and the 3' splice site. Thailanstatin D exhibits a potent tumor inhibitory effect on human CRPC xenografts leading to cell apoptosis[1].

  • CAS Number: 1609105-89-6
  • MF: C28H41NO8
  • MW: 519.63
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZL-2201

ZL-2201 is a potent DNA-PK inhibitor with an IC50 of 1 nM (WO2021104277A1, compound 5)[1].

  • CAS Number: 2865115-39-3
  • MF: C20H25N9O5S
  • MW: 503.53
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Darglitazone

Darglitazone (CP-86325), a thiazolidinedione, is a potent, selective, and orally active PPAR-γ agonist. Darglitazone is effective in controlling blood glucose and lipid metabolism, and can be used for type II diabetes research[1].

  • CAS Number: 141200-24-0
  • MF: C23H20N2O4S
  • MW: 420.48100
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ganciclovir sodium

Ganciclovir (BW 759) sodium, a nucleoside analogue and an orally active antiviral agent, shows activity against CMV. Ganciclovir sodium also has activity in vitro against members of the herpes group and some other DNA viruses. Ganciclovir sodium inhibits the in vitro replication of human herpes viruses (HSV 1 and 2, CMV) and adenovirus serotypes 1, 2, 4, 6, 8, 10, 19, 22 and 28. Ganciclovir sodium has an IC50 of 5.2 μM for feline herpesvirus type-1 (FHV-1)[1][2][3].

  • CAS Number: 107910-75-8
  • MF: C9H12N5NaO4
  • MW: 277.212
  • Catalog: CMV
  • Density: 1.81g/cm3
  • Boiling Point: 675ºC at 760mmHg
  • Melting Point: 250ºC (decomposition)
  • Flash Point: 362ºC

PROTAC HDAC6 degrader 1

PROTAC HDAC6 degrader (Compound A6) is a potent and selective PROTAC HDAC6 degrader with a DC50 of 3.5 nM. PROTAC HDAC6 degrader shows promising antiproliferative activity via inducing apoptosis in myeloid leukemia cell lines[1].

  • CAS Number: 2785404-76-2
  • MF: C37H46N6O10
  • MW: 734.80
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carmustine

Carmustine is an antitumor chemotherapeutic agent, which works by akylating DNA and RNA.

  • CAS Number: 154-93-8
  • MF: C5H9Cl2N3O2
  • MW: 214.050
  • Catalog: DNA Alkylator/Crosslinker
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 404ºC
  • Melting Point: 30 °C(lit.)
  • Flash Point: N/A

RAD51-IN-4

RAD51-IN-4 is a potent inhibitor of RAD51. RAD51 is a eukaryote gene. RAD51-IN-4 has the potential for the research of conditions involving mitochondrial defects (extracted from patent WO2019014315A1, compound R12)[1].

  • CAS Number: 2267336-26-3
  • MF: C31H34FN5O5S2
  • MW: 639.76
  • Catalog: RAD51
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nicotinamide riboside tartrate

Nicotinamide riboside tartrate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside tartrate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities[1]. Nicotinamide riboside tartrate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease[2].

  • CAS Number: 2415657-86-0
  • MF: C15H20N2O11
  • MW: 404.33
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

9-cis-Retinoic acid-d5

9-cis-Retinoic acid-d5 (ALRT1057-d5) is the deuterium labeled 9-cis-Retinoic acid. 9-cis-Retinoic acid (ALRT1057), a vitamin A derivative, is a potent RAR/RXR agonist. 9-cis-Retinoic acid induces apoptosis, regulates cell cycle and has anticancer, anti-inflammatory and neuroprotection activities[1][2][3][4][5][6].

  • CAS Number: 78996-15-3
  • MF: C20H23D5O2
  • MW: 305.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIRT5 inhibitor 7

SIRT5 inhibitor 7 (compound 58) is a substrate-competitive and selective SIRT5 inhibitor with anti-inflammatory activity. SIRT5 inhibitor 7 has renal protective effects and regulates protein succinylation and the release of pro-inflammatory cytokines. SIRT5 inhibitor 7 has in vivo activity in AKI mouse models of lipopolysaccharide (LPS) and cecal ligation/perforation (CLP)-induced sepsis-related acute kidney injury[1].

  • CAS Number: 2951090-00-7
  • MF: C28H32ClN7O3S
  • MW: 582.12
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A