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
Cytoskeleton >
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ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
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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 >
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5-Fluorouracil-13C,15N2

5-Fluorouracil-13C,15N2 is the 13C and 15N labeled 5-Fluorouracil[1]. 5-Fluorouracil (5-FU) is an analogue of uracil and a potent antitumor agent. 5-Fluorouracil affects pyrimidine synthesis by inhibiting thymidylate synthetase thus depleting intracellular dTTP pools. 5-Fluorouracil induces apoptosis and can be used as a chemical sensitizer[2][3]. 5-Fluorouracil also inhibits HIV[4].

  • CAS Number: 1189423-58-2
  • MF: C313CH3F15N2O2
  • MW: 133.057
  • Catalog: HIV
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IC 261

IC261 is a selective, ATP-competitive CK1 inhibitor, with IC50s of 1 μM, 1 μM, 16 μM for Ckiδ, Ckiε and Ckiα1, respectively.

  • CAS Number: 186611-52-9
  • MF: C18H17NO4
  • MW: 311.332
  • Catalog: Casein Kinase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 555.2±50.0 °C at 760 mmHg
  • Melting Point: 214 °C
  • Flash Point: 289.6±30.1 °C

1-[4-hydroxy-3-trityloxy-5-(trityloxymethyl)oxolan-2-yl]pyrimidine-2,4-dione

2',5'-Bis-O-(triphenylMethyl)uridine is a uridine analog. Uridine has potential antiepileptic effects, and its analogs can be used to study anticonvulsant and anxiolytic activities, as well as to develop new antihypertensive agents[1].

  • CAS Number: 6554-11-6
  • MF: C47H40N2O6
  • MW: 728.83
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.33g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2',3',5'-Tri-O-benzoyl-5-Methoxyuridine

2’,3’,5’-Tri-O-benzoyl-5-methoxyuridine 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: 37805-86-0
  • MF: C31H26N2O10
  • MW: 586.55
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Combretastatin A4 disodium phosphate

Fosbretabulin disodium(CA 4DP; CA 4P) is a microtubule destabilizing drug, a type of vascular-targeting agent, a drug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis.IC50 Value: 4 nM [1]Target: microtubulein vitro: Cytotoxic IC(50) values of CA-4 in human bladder cancer cells were below 4 nM. Analyses of cell-cycle distribution showed CA-4 obviously induced G(2)-M phase arrest with sub-G(1) formation. The analyses of apoptosis showed that CA-4 induced caspase-3 activation and decreased BubR1 and Bub3 in cancer cells [1]. The enhanced apoptosis induced by dasatinib plus CA-4 was accompanied by a greater extent of mitochondrial depolarization, caspase-3 activation and PARP cleavage in HO-8910 cells. Furthermore, elevated expression of Mcl-1 led to a reduced apoptosis induced by dasatinib plus CA-4, highlighting that downregulated Mcl-1 was necessary for the potentiating effect of dasatinib to CA-4-triggered apoptosis [2].in vivo: The increased anticancer efficacy of dasatinib combined with CA-4 was further validated in a human HO-8910 ovarian cancer xenograft model in nude mice [2]. There was a significant, concentration dependent increase in mean arterial blood pressure with a maximum increase of about 60% of the baseline MAP at 30 mg/kg of CA4P compared to the saline control. However, there was no significant increase in the cardiac troponin I level after CA4P injection [3].Clinical trial: A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome [4].

  • CAS Number: 168555-66-6
  • MF: C18H19Na2O8P
  • MW: 440.292
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: 611.8ºC at 760 mmHg
  • Melting Point: 238-242ºC
  • Flash Point: N/A

5-Azidomethyl-2’-beta-methyl uridine

5-Azidomethyl-2’-beta-methyl uridine 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: 2305415-72-7
  • MF: C11H15N5O6
  • MW: 313.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rhodblock 6

Rhodblock 6 is a Rho kinase (ROCK) inhibitor that inhibits phospho-MRLC (myosin regulatory light chain) localization[1].

  • CAS Number: 886625-06-5
  • MF: C12H13N3O
  • MW: 215.25
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-4827 tosylate

Niraparib tosylate (MK-4827 tosylate) is an excellent PARP1 and PARP2 inhibitor with an IC50 of 3.8 and 2.1 nM, respectively.

  • CAS Number: 1038915-73-9
  • MF: C26H28N4O4S
  • MW: 492.59000
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Bromoquinazoline-2,4-diamine

DHFR-IN-3 is a dihydrofolate reductase (DHFR) inhibitor with the IC50 values of 19 μM and 12 μM in rat liver and P. carinii DHFR, respectively[1].

  • CAS Number: 137553-43-6
  • MF: C8H7BrN4
  • MW: 239.072
  • Catalog: Antifolate
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 509.4±58.0 °C at 760 mmHg
  • Melting Point: 255-256°C
  • Flash Point: 261.9±32.3 °C

ADTL-SA1215

ADTL-SA1215 is a first-in-class specific small-molecule activator of SIRT3 that modulates autophagy in triple negative breast cancer.

  • CAS Number: 782387-91-1
  • MF: C26H29I2NO3
  • MW: 657.32
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antitumor agent-28

Antitumor agent-28 selectively inhibits ataxia telangiectasia mutated (ATM) kinase. Antitumor agent-28 prevents ATM mediated disease and has potent anti-cancer activity[1].

  • CAS Number: 2097499-67-5
  • MF: C25H32N6O4S
  • MW: 512.62
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DM4-SMe

DM4-SMe is a metabolite of antibody-maytansin conjugates (AMCs) and a tubulin inhibitor, and also a cytotoxic moiety of antibody-drug conjugates (ADCs), which can be linked to antibody through disulfide bond or stable thioether bond. DM4-SMe inhibits KB cells with an IC50 of 0.026 nM[1][2].

  • CAS Number: 796073-68-2
  • MF: C39H56ClN3O10S2
  • MW: 826.45900
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3’-Deoxy-3’-fluoro-N6-methyladenosine

3’-Deoxy-3’-fluoro-N6-methyladenosine 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: 122654-27-7
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10746

CAY10746 is a selective Rho kinase (ROCK) inhibitor. CAY10746 has inhibitory activity for ROCK I, ROCK II with IC50 values of 0.014 μM and 0.003 μM, respectively. CAY10746 can be used for the research of diabetic retinopathy (DR)[1].

  • CAS Number: 2247240-76-0
  • MF: C26H23N3O5
  • MW: 457.478
  • Catalog: ROCK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 664.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.5±31.5 °C

MF-094

MF-094 is a potent and selective USP30 inhibitor with an IC50 of 120 nM.

  • CAS Number: 2241025-68-1
  • MF: C30H37N3O4S
  • MW: 535.70
  • Catalog: Deubiquitinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5'-DMT-N2-DMF-dG

5'-O-DMT-2'-O-TBDMS-rI is a modified nucleoside. 5'-O-DMT-2'-O-TBDMS-rI can be used in the synthesis of deoxyribonucleic acid or nucleic acid.

  • CAS Number: 40094-22-2
  • MF: C34H36N6O6
  • MW: 624.68600
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDK2-IN-14-d3

CDK2-IN-14-d3 (compound 5f) is a potent and selective CDK2 inhibitor. CDK2-IN-14-d3 can be used in research of cancer[1].

  • CAS Number: 2498658-25-4
  • MF: C21H22D3N5O4S
  • MW: 446.54
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2'-O-MOE-N2-ibu-rG

N2-iso-Butyryl-2'-O-(2-methoxyethyl)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: 440327-50-4
  • MF: C17H25N5O7
  • MW: 411.41
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF 5006739

PF-5006739 is a potent and selective inhibitor of CK1δ/ε with IC50s of 3.9 nM and 17.0 nM, respectively. PF-5006739 is a potential therapeutic agent for a range of psychiatric disorders with low nanomolar in vitro potency for CK1δ/ε and high kinome selectivity. PF-5006739 attenuats opioid drug-seeking behavior in a rodent operant reinstatement model in animals in a dose-dependent manner[1]. PF-5006739 improves glucose tolerance in both diet-induced obesity (DIO) and genetic (ob/ob) mice models of obesity[2].

  • CAS Number: 1293395-67-1
  • MF: C22H22FN7O
  • MW: 419.455
  • Catalog: Casein Kinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 680.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.6±34.3 °C

2’-Chloro-N6-(3-methoxy)benzyl adenosine

2’-Chloro-N6-(3-methoxy)benzyl adenosine 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: 722504-73-6
  • MF: C18H20ClN5O5
  • MW: 421.83
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubulin polymerization-IN-10

Tubulin polymerization-IN-10 is a potent tubulin polymerization inhibitor with an IC50 of 4.25±0.75 μM. Tubulin polymerization-IN-10 has anti-tumor effects[1].

  • CAS Number: 2238784-19-3
  • MF: C18H21NO6S
  • MW: 379.43
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zorubicin

Zorubicin (Rubidazon) is a derivative of Daunorubicin (HY-13062A). Zorubicin interacts with topoisomerase II and inhibits DNA polymerases. Zorubicin can be used for the research of acute leukemias and sarcomas[1][2][3][4][5].

  • CAS Number: 54083-22-6
  • MF: C34H35N3O10
  • MW: 645.65600
  • Catalog: DNA/RNA Synthesis
  • Density: 1.54g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aminopurvalanol A

Aminopurvalanol A is a potent, selective, and cell permeable inhibitor of Cyclins/Cdk complexes. Aminopurvalanol A preferentially targets the G2/M-phase transition inhibiting cancer cell differentiation. Aminopurvalanol A causes the inhibition of sperm fertilizing ability via the inhibition of physiological capacitation-dependent actin polymerization[1][2].

  • CAS Number: 220792-57-4
  • MF: C19H26ClN7O
  • MW: 403.90900
  • Catalog: Apoptosis
  • Density: 1.4g/cm3
  • Boiling Point: 639ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 340.2ºC

Quinizarin

Quinizarin (1,4-Dihydroxyanthraquinone), a part of the anticancer agents such as Doxorubicin, Daunorubicin, and Adriamycin, interacts with DNA by intercalating mode (Kd=86.1 μM). Quinizarin is used as a fungicide and pesticide chemical and has shown the ability to inhibit tumor cell growth[1][2].

  • CAS Number: 81-64-1
  • MF: C14H8O4
  • MW: 240.211
  • Catalog: Fungal
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 465.3±40.0 °C at 760 mmHg
  • Melting Point: 198-199 °C(lit.)
  • Flash Point: 249.3±23.8 °C

EHT 5372

EHT 5372 is a strong inhibitor of DYRK’s family kinases, with IC50s of 0.22, 0.28 nM for DYRK1A and DYRK1B, respectively.

  • CAS Number: 1425945-60-3
  • MF: C18H14FN5O2S
  • MW: 383.40
  • Catalog: CDK
  • 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-xylo-guanosine

7,8-Dihydro-8-oxo-7-propargyl-3’-deoxy-3’-fluoro-xylo-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: 2389988-56-9
  • MF: C13H14FN5O5
  • MW: 339.28
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-3 inhibitor 4

GSK-3 inhibitor 4 is an orally active and brain-penetrant inhibitor of GSK-3, CDK2, and CDK5, with IC50 values of 0.56 nM (GSK-3β), 0.45 nM (GSK-3α), 0.47 μM, and 0.68 μM, respectively. GSK-3 inhibitor 4 effectively reduces the phosphorylation level of Tau protein. GSK-3 inhibitor 4 can be used in Alzheimer's disease (AD) studies[1].

  • CAS Number: 2227279-83-4
  • MF: C22H15F2N5O
  • MW: 403.38
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cytidine, N-methyl-

N4-Methylcytidine (Nsc518744) 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: 10578-79-7
  • MF: C10H15N3O5
  • MW: 257.24
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.69g/cm3
  • Boiling Point: 504.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 258.7ºC

CDK4/6-IN-2

CDK4/6-IN-2 is a potent CDK4 and CDK6 inhibitor extracted from patent US20180000819A1, Compound 1, has IC50s of 2.7 and 16 nM for CDK4 and CDK6, respectively[1].

  • CAS Number: 1800506-48-2
  • MF: C27H32F2N8
  • MW: 506.59
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bohemine

Bohemine is a purine analogue and is a synthetic and selective CDK inhibitor with IC50s of 4.6 μM, 83 μM, and 2.7 μM for Cdk2/cyclin E, Cdk2/cyclin A, and Cdk9/cyclin T1, respectively. Bohemine also inhibits ERK2 with an IC50 of 52 μM and has less inhibitory effect on CDK1, CDK4 and CDK6. Bohemine has a broad spectrum anti-cancer activities[1][2].

  • CAS Number: 189232-42-6
  • MF: C18H24N6O
  • MW: 340.423
  • Catalog: CDK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 589.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 310.3±32.9 °C