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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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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isoCA-4

isoCA-4, a Combretastatin A4 derivative, is a tubulin polymerization inhibitor. isoCA-4 has anti-proliferative activities[1].

  • CAS Number: 1067880-31-2
  • MF: C18H20O5
  • MW: 316.35
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SEW84

SEW84 (SEW04784) is a first-in-class, specific inhibitor of the Aha1-stimulated Hsp90 (ASH) ATPase activity (IC50=0.3 uM) without inhibiting basal Hsp90 ATPase;SEW84 binds to the C-terminal domain of Aha1 (Kd=1.7 uM) to weaken its asymmetric binding to Hsp90.SEW84 inhibited the GR- and AR-dependent luciferase expression with IC50 of 1.3 uM and 0.7 uM respectively.SEW84 blocks Aha1-dependent Hsp90 chaperoning activities, including the in vitro and in vivo refolding of firefly luciferase, and the transcriptional activity of the androgen receptor in cell-based models of prostate cancer.SEW84 promotes the clearance of phosphorylated tau in cellular and tissue models of neurodegenerative tauopathy.

  • CAS Number: 259089-67-3
  • MF: C19H14F4N4Os
  • MW: 422.402
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anticancer agent 71

Anticancer agent 71 (Compound 4b) is a potent anticancer agent and induces apoptosis. Anticancer agent 71 arrests cell cycle at G2/M phase and induces apoptosis through upregulating Bax, Ikb-α and cleaved PARP and downregulating Bcl-2 expression levels. Anticancer agent 71 shows antiproliferative activity[1].

  • CAS Number: 2453228-45-8
  • MF: C18H13ClF3N5O
  • MW: 407.78
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GW 1929 hydrochloride

GW1929 hydrochloride is an orally active peroxisome proliferator-activated receptor-γ (PPARγ) agonist with a pKi of 8.84 for human PPAR-γ, and pEC50s of 8.56 and 8.27 for human PPAR-γ and murine PPAR-γ, respectively. GW1929 hydrochloride has antidiabetic efficacy and neuroprotective potential. GW1929 hydrochloride suppresses neuronal apoptosis and shows anti-inflammatory potential[1][2][3].

  • CAS Number: 1217466-21-1
  • MF: C30H30ClN3O4
  • MW: 532.030
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TOS-ARG-OME.HCL

TAME hydrochloride is an inhibitor of anaphase-promoting complex (APC), which prevents its activation by Cdc20 and Cdh1.

  • CAS Number: 1784-03-8
  • MF: C14H23ClN4O4S
  • MW: 378.875
  • Catalog: APC
  • Density: N/A
  • Boiling Point: 544.1ºC at 760mmHg
  • Melting Point: 145-147(lit.)
  • Flash Point: 282.9ºC

N-(3-Chlorophenyl)-2-(4-(4-chlorophenyl)-1-oxophthalazin-2(1H)-yl)acetamide

PARP-1-IN-2 (compound 11g) is a potent and BBB-penetrated PARP1 inhibitor, with an IC50 of 149 nM. PARP1-IN-2 shows significantly potent anti-proliferative activity against Human lung adenocarcinoma epithelial cell line A549. PARP1-IN-2 can induce A549 cells apoptosis[1].

  • CAS Number: 684234-55-7
  • MF: C22H15Cl2N3O2
  • MW: 424.28
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BS194

BS-194 is an orally active, selective and potent CDK inhibitor. BS-194 inhibits CDK2, CDK1, CDK5, CDK7, and CDK9 (IC50s: 3, 30, 30, 250, and 90 nM respectively). BS-194 potently inhibits cancer cells proliferation. BS-194 can be used in the research of cancers like breast cancer, colon cancer[1].

  • CAS Number: 1092443-55-4
  • MF: C20H27N5O3
  • MW: 385.460
  • Catalog: CDK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mavodelpar

Mavodelpar (REN001) is a selective PPARδ agonist. Mavodelpar suppresses glomerular injury and renal fibrosis. Mavodelpar can be used for the research of primary mitochondrial myopathies (PMM) and long-chain fatty acid oxidation disorders (LC-FAOD)[1].

  • CAS Number: 1604815-32-8
  • MF: C31H29FNNaO5
  • MW: 537.55
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KT-531

KT-531 (KT531) is a potent, selective HDAC6 inhibitor with IC50 of 8.5 nM, displays 39-fold selectivity.

  • CAS Number: 2490284-18-7
  • MF: C17H14F4N2O4S
  • MW: 418.363
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

I-138

I-138 is an orally active compound structurally related to ML323 (HY-17543). I-138 and ML-323 are potent reversible inhibitors of USP1-UAF1. I-138 displays synergistic binding with ubiquitin and mutual exclusive binding with ML323. I-138 induces the monoubiquitination of FANCD2 and PCNA in MDA-MB-436 cells, increases PCNA and FANCD2 monoubiquitination in HAP-1 USP1 WT cells. I-138 ablates USP1 autocleavage in cells[1].

  • CAS Number: 2098211-50-6
  • MF: C26H23F3N6O
  • MW: 492.50
  • Catalog: Deubiquitinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tesetaxel

Tesetaxel is a orally active, semisynthetic microtubule inhibitor of the taxane class for the treatment of cancer, including colorectal and gastric cancer.

  • CAS Number: 333754-36-2
  • MF: C46H60FN3O13
  • MW: 881.99
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

para-TOPOLIN RIBOSIDE(pTR)

N6-(4-Methoxybenzyl)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: 23666-24-2
  • MF: C18H21N5O5
  • MW: 387.39
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ganoderic acid D

Ganoderic acid D, a highly oxygenated tetracyclic triterpenoid, is the major active component of Ganoderma lucidum. Ganoderic acid D upregulates the protein expression of SIRT3 and induces the deacetylated cyclophilin D (CypD) by SIRT3. Ganoderic acid D inhibits the energy reprogramming of colon cancer cells including glucose uptake, lactate production, pyruvate and acetyl-coenzyme production in colon cancer cells[1]. Ganoderic acid D can inhibit the growth of numerous cancer cell lines and it inhibits HeLa human cervical carcinoma cells with an IC50 of 17.3 mM[2].

  • CAS Number: 108340-60-9
  • MF: C30H42O7
  • MW: 514.650
  • Catalog: Sirtuin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 688.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.1±28.0 °C

2-Amino-6-chloropurine-9-beta-D-(2’-deoxy-2’-fluoro)-arabinoriboside

2-Amino-6-chloropurine-9-beta-D-(2’-deoxy-2’-fluoro)-arabinoriboside 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: 144924-88-9
  • MF: C10H11ClFN5O3
  • MW: 303.68
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-O-Methyldeoxyguanosine

O6-Methyldeoxy guanosine; DNA adduct 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: 964-21-6
  • MF: C11H15N5O4
  • MW: 281.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.84 g/cm3
  • Boiling Point: 674.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 361.9ºC

OSS_128167

OSS_128167 is a selective SIRT6 inhibitor with IC50s of 89, 1578 and 751 μM for SIRT6, SIRT1 and SIRT2, respectively.

  • CAS Number: 887686-02-4
  • MF: C19H14N2O6
  • MW: 366.32
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D-Xylofuranose, 1,2,3,5-tetraacetate

D-Xylofuranose, 1,2,3,5-tetraacetate is the raw material for nucleotides synthesis[1].

  • CAS Number: 42927-46-8
  • MF: C13H18O9
  • MW: 318.27700
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3'-Azido-3'-deoxy-beta-L-uridine

3'-Azido-3'-deoxy-beta-L-uridine (Compound 25) is a nucleoside derivative.

  • CAS Number: 2095417-28-8
  • MF: C9H11N5O5
  • MW: 269.21
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Folinic acid

Folinic acid is an adjuvant used in cancer chemotherapy involving the drug methotrexate.Target: AntifolateFolinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate), and, thus, has vitamin activity that is equivalent to that of folic acid. Since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by inhibition of this enzyme by drugs such as methotrexate. In 1980s, however, folinic acid was found to reactivate the dihydrofolate reductase itself even when methotrexate exists. Although the mechanism is not very clear, the polyglutamylation of methotrexate and dihydrofolate in malignant cells is considered to play an important role in the selective reactivation of dihydrofolate reductase by folinic acid in normal cells [1]. Folinic acid is generally administered along with MTX as a rescue agent to decrease MTX-induced toxicity. However, information regarding the inhibitory effect of folinic acid against cytogenetic damage caused by MTX is limited. This study was conducted to assess the cytogenetic effect of MTX and its inhibition by folinic acid (FA) using the micronucleus and chromosomal aberration assays concurrently [2].

  • CAS Number: 58-05-9
  • MF: C20H23N7O7
  • MW: 473.43900
  • Catalog: Antifolate
  • Density: 1.68g/cm3
  • Boiling Point: N/A
  • Melting Point: 245ºC (decomp)
  • Flash Point: N/A

KW-2449

KW-2449 is a multi-targeted kinase inhibitor of FLT3, ABL, ABLT315I and Aurora kinase with IC50s of 6.6, 14, 4 and 48 nM, respectively.

  • CAS Number: 1000669-72-6
  • MF: C20H20N4O
  • MW: 332.399
  • Catalog: Aurora Kinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 604.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 319.1±31.5 °C

Tempo-d18

Tempo-d18 is the deuterium labeled Tempo[1]. Tempo is a classic nitroxide radical and is a selective scavenger of ROS that dismutases superoxide in the catalytic cycle. Tempo induces DNA-strand breakage. Tempo can be used as an organocatalyst for the oxidation of primary alcohols to aldehydes. Tempo has mutagenic and antioxidant effects[2][3][4][5].

  • CAS Number: 205679-68-1
  • MF: C9D18NO*
  • MW: 174.356232004
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDK8-IN-7

CDK8-IN-7 (compound 12) is a potent and selective cyclin-dependent kinase 8 (CDK8) inhibitor with an Kd of 3.5 nM. CDK8-IN-7 shows cytotoxicity for MOLM-13, OCI-AML3, MV4-11, NRK and H9c2 cells with IC50s of 5.9, 4.8, 5.4, 16.2, 12.5-25 µM, respectively. CDK8-IN-7 has the potential for the research of AML-cancer[1].

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

proguanil hydrochloride

Proguanil hydrochloride, an antimalarial prodrug, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil hydrochloride is a dihydrofolate reductase (DHFR) inhibitor[1][2].

  • CAS Number: 637-32-1
  • MF: C11H17Cl2N5
  • MW: 290.192
  • Catalog: Antifolate
  • Density: N/A
  • Boiling Point: 402.7ºC at 760 mmHg
  • Melting Point: 249-251ºC
  • Flash Point: 197.4ºC

Voruciclib hydrochloride

Voruciclib hydrochloride is a clinical stage oral CDK9 inhibitor. Voruciclib hydrochloride represses expression of MCL-1 in multiple models of diffuse large B-cell lymphoma (DLBCL)[1].

  • CAS Number: 1000023-05-1
  • MF: C22H20Cl2F3NO5
  • MW: 506.30
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MPI-0479605

MPI-0479605 is a potent and selective ATP-competitive inhibitor of Mps1, with an IC50 of 1.8 nM.

  • CAS Number: 1246529-32-7
  • MF: C22H29N7O
  • MW: 407.512
  • Catalog: Mps1
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2’-β-C-Ethynylcytidine

2’-β-C-Ethynylcytidine 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: 188413-99-2
  • MF: C11H13N3O5
  • MW: 267.24
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 536.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.2±32.9 °C

2’,3’,5’-Tri-O-acetyl-5-cyanouridine

2’,3’,5’-Tri-O-acetyl-5-cyanouridine 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: 1630743-99-5
  • MF: C16H17N3O9
  • MW: 395.32
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kongensin A

Kongensin A is a natural product isolated from Croton kongensis. Kongensin A is an effective, covalent HSP90 inhibitor that blocks RIP3-dependent necroptosishas. Kongensin A is a potent necroptosis inhibitor and an apoptosis inducer. Kongensin A has potential anti-necroptosis and anti-inflammation applications[1].

  • CAS Number: 885315-96-8
  • MF: C22H30O5
  • MW: 374.471
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 525.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 178.4±23.6 °C

Vinblastine Sulfate

Vinblastine sulfate is a cytotoxic alkaloid used against various cancer types. Vinblastine sulfate inhibits the formation of microtubule and suppresses nAChR with an IC50 of 8.9 μM.

  • CAS Number: 143-67-9
  • MF: C46H60N4O13S
  • MW: 909.053
  • Catalog: Autophagy
  • Density: 1.37 g/cm3
  • Boiling Point: N/A
  • Melting Point: 267 °C (dec.)(lit.)
  • Flash Point: N/A

ER degrader 7

ER degrader 7 (Compound 35t) is an ERα and ERβ degrader. ER degrader 7 inhibits tubulin polymerization. ER degrader 7 inhibits cell viability with IC50s of 0.06, 2.56, 15.84, 1.59, 1.67, 1.37 μM for MCF-7, T47D, MCF-10A, LCC2, T47D D538G, and T47D Y537S cells respectively. ER degrader 7 also inhibits breast cancer tumor growth[1].

  • CAS Number: 2922929-63-1
  • MF: C33H31F4N3O5SSe
  • MW: 736.63
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A