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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3’-O-(t-Butyldiphenylsilyl) thymidine

3’-O-(t-Butyldiphenylsilyl) thymidine 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: 83467-48-5
  • MF: C10H13DTBN2O5PS
  • MW: 320.10
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(1S)-1,4-Anhydro-1-C-(2,4-difluorophenyl)-D-ribitol

(1S)-1,4-Anhydro-1-C-(2,4-difluorophenyl)-D-ribitol 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: 263701-23-1
  • MF: C11H12F2O4
  • MW: 246.21
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 395.9±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 179.8±24.4 °C

7-Epi-10-oxo-docetaxel

7-Epi-10-oxo-docetaxel (Docetaxel Impurity D) is a impurity of docetaxel detected by high performance liquid chromatography (HPLC).

  • CAS Number: 162784-72-7
  • MF: C43H51NO14
  • MW: 805.86300
  • Catalog: Microtubule/Tubulin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 887.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 490.4±34.3 °C

ABT-751 (E7010)

ABT-751(E 7010) is a novel bioavailable tubulin-binding and antimitotic sulfonamide agent with IC50 of about 1.5 and 3.4 μM in neuroblastoma and non-neuroblastoma cell lines, respectively.IC50 Value: 1.5 μM(neuroblastoma); 3.4 μM(non-neuroblastoma)Target: Microtubule/Tubulinin vitro: ABT-751 shows the selective cytotoxicity with IC50 of 0.6–2.6 μM in neuroblastoma and 0.7–4.6 μM in other solid tumor cell lines. Furthermore, ABT-751 also exhibits a selective effect on dynamic microtubules and spares stable microtubules, accounting for the persistence of acetylated and detyrosinated α-tubulin positive polymerized tubules at the IC90 concentration of ABT-751. in vivo: In Calu-6 xenograft model, ABT-751 as a single agent at 100 and 75 mg/kg/day shows significant antitumor activity, while in combination with cisplatin, ABT-751 shows a dose-dependent enhancement in growth delay. In the HT-29 colon xenograft model, ABT-751 also shows significant antitumor activity as a single agent and produced a dose-dependent enhancement in growth delay In combination with 5-FU. In dogs with lymphoma, ABT-751 exhibits the dose-limiting toxicities that included vomiting, diarrhea, anorexia, or some combination of these with a maximum tolerated dose (MTD) of 350 mg/m2 PO q24h. Furthermore, the mean AUC and Cmax for ABT-751 at the MTD of 350 mg/m2 is 5.55 μg-hour/mL and 0.9 μg/mL, respectively.

  • CAS Number: 141430-65-1
  • MF: C18H17N3O4S
  • MW: 371.410
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 551.0±60.0 °C at 760 mmHg
  • Melting Point: 162 °C(dec.)
  • Flash Point: 287.0±32.9 °C

Parbendazole

Parbendazole is a potent inhibitor of microtubule assembly, destabilizes tubulin, with an EC50 of 8.79 nM, and exhibits a broad-spectrum anthelmintic activity.

  • CAS Number: 14255-87-9
  • MF: C13H17N3O2
  • MW: 247.293
  • Catalog: Microtubule/Tubulin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 255-257°C
  • Flash Point: N/A

3-Oxo-4-(?D-ribofuranosyl)-3,4-dihydro-2-pyrazinecarboxamide

3,4-Dihydro-3-oxo-4-β-D-ribofuranosyl-2-pyrazinecarboxamide 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: 356782-84-8
  • MF: C10H13N3O6
  • MW: 271.23
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sirt1/2-IN-3

Sirt1/2-IN-3 (compound PS9) is a dual inhibitor of SIRT1/2 with IC50s of 1.4 μM (SIRT1) and 2.0 μM (SIRT2), respsectivley. Sirt1/2-IN-3 completely blocks p53 deacetylation, and increase of p53 and α-tubulin acetylation. Sirt1/2-IN-3 induces apoptosis and shows anti-proliferation activity against human leukemia cell lines[1].

  • CAS Number: 301313-42-8
  • MF: C17H14ClNO4S
  • MW: 363.82
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antiproliferative agent-30

Antiproliferative agent-30 (Compound 8g) inhibits tubulin assembly and inhibits FLT3 and Abl1. Antiproliferative agent-30 has vascular-disrupting activity. Antiproliferative agent-30 has broad antiproliferative activities against cancer cell lines (IC50s: 0.054 nM, 0.008 nM, 0.144 nM for HCT-116, K562, MV-4-11 cells respectively). Antiproliferative agent-30 also has anticancer effect against AML with FLT3-ITD-TKD mutation[1].

  • CAS Number: 2713553-88-7
  • MF: C24H26N4O4
  • MW: 434.49
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Edaglitazone

Edaglitazone is a potent, selective and orally active PPARγ agonist, with EC50s of 35.6 nM and 1053 nM for PPARα and PPARγ, respectively. Edaglitazone displays antiplatelet, antidiabetic and anti-hyperglycemic activity[1][2][3].

  • CAS Number: 213411-83-7
  • MF: C24H20N2O4S2
  • MW: 464.56
  • Catalog: PPAR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sirt1/2-IN-2

Sirt1/2-IN-2 (compound hsa55) is a dual inhibitor of SIRT1/2 with IC50s of 1.8 μM (SIRT1) and 2.4 μM (SIRT2), respsectivley. Sirt1/2-IN-2 completely blocks p53 deacetylation, and increase of p53 and α-tubulin acetylation. Sirt1/2-IN-2 induces apoptosis and shows anti-proliferation activity against human leukemia cell lines[1].

  • CAS Number: 670267-73-9
  • MF: C18H14N4O3S2
  • MW: 398.46
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2’-Deoxy-2’-fluoro-N3-[(pyrid-4-yl)methyl]-beta-D-arabinouridine

2’-Deoxy-2’-fluoro-N3-[(pyrid-4-yl)methyl]-beta-D-arabinouridine 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: 2072145-47-0
  • MF: C15H18FN3O4
  • MW: 323.32
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

7,8-Dihydro-8-oxo-7-propargyl-3’-deoxy 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: 2389988-54-7
  • MF: C13H15N5O5
  • MW: 321.29
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DNL343

DNL343 is a brain-penetrating activator of eukaryotic initiation factor 2B (eIF2B) that inhibits the abnormal integrated stress response (ISR). DNL343 inhibits ISR activity in the central nervous system (CNS) and reverses neurodegeneration and neuroinflammation. DNL343 also prevents motor dysfunction and premature death in eIF2B loss-of-function (LOF) mutant mice. DNL343 has inhibitory potential in studies of vanishing white matter disease (VWMD) driven by eIF2B LOF and chronic ISR activation[1].

  • CAS Number: 2278265-85-1
  • MF: C20H19ClF3N3O4
  • MW: 457.83
  • Catalog: Eukaryotic Initiation Factor (eIF)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AQ4

AQ4 is a topoisomerase II inhibitor and DNA intercalator as a chemically stable cytotoxic agent in many human tumor lines[1].

  • CAS Number: 70476-63-0
  • MF: C22H28N4O4
  • MW: 412.48200
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carboxycinnamic acid bishydroxamide

m-Carboxycinnamic acid bishydroxamide is a potent HDAC inhibitor, exhibiting ID50 values of 10 and 70 nM in vitro for HDAC1 and HDAC3, respectively[1]. m-Carboxycinnamic acid bishydroxamide also induces apoptosis and suppresses tumor growth[2].

  • CAS Number: 174664-65-4
  • MF: C10H10N2O4
  • MW: 222.20
  • Catalog: HDAC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDK7/12-IN-1

CDK7/12-IN-1 is a selective CDK7/12 inhibitor with IC50s of 3 and 277 nM for CDK7 and CDK 12, respectively. CDK7 and CDK12 inhibition is an effective strategy to inhibit tumour growth[1].

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

Taq DNA polymerase

Taq DNA polymerase is a thermostable DNA polymerase that can be used in PCR[1].

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

E-7449

E7449 is a potent PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC50s of 2.0, 1.0, ∼50 and ∼50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively, using 32P-NAD+ as substrate.

  • CAS Number: 1140964-99-3
  • MF: C18H15N5O
  • MW: 317.345
  • Catalog: PARP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 381.4±34.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 184.5±25.7 °C

CKD-516

Valecobulin hydrochloride (CKD-516 hydrochloride) is a valine prodrug of S516 (HY-130233) and a vascular disrupting agent (VDA). Valecobulin hydrochloride is a potent β-tubulin polymerization inhibitor with marked antitumor activity against murine and human solid tumors[1][2].

  • CAS Number: 1240321-53-2
  • MF: C26H29ClN6O5S
  • MW: 573.06400
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bocidelpar

Bocidelpar is a modulator of peroxisome proliferator-activated receptor delta (PPAR-δ). Bocidelpar improves mitochondrial biogenesis and function in Duchenne Muscular Dystrophy (DMD) muscle cells (extracted from patent WO2017062468A1, compound 2b)[1].

  • CAS Number: 2095128-20-2
  • MF: C25H27F3N2O3
  • MW: 460.49
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: 613.4±65.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Thiazovivin

Thiazovivin is a potent ROCK inhibitor, which can protect human embryonic stem cells.

  • CAS Number: 1226056-71-8
  • MF: C15H13N5OS
  • MW: 311.362
  • Catalog: ROCK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antitumor agent-71

Antitumor Agent-71 is an antiproliferative activity antitumor agent and against tumor cell lines with IC50 values ranging from 3.98-15.70 μM. Antitumor Agent-71 is an antitumor agent that can inhibit tubulin polymerization.

  • CAS Number: 2011756-99-1
  • MF: C26H31N5O4S
  • MW: 509.62
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1374107-46-6

THK-5105, an arylquinoline derivative, displays high binding affinity to tau fibrils. THK-5105 has high binding affinity to tau protein aggregates and tau-rich Alzheimer disease (AD)  brain homogenates. 18F-THK-5105 has the potential to act as a tau imaging PET probe[1].

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

SSE15206

SSE15206 is a microtubule polymerization inhibitor, with a GI50 of 197 nM in a SRB proliferation assay in HCT116 cells.

  • CAS Number: 1370046-40-4
  • MF: C19H21N3O3S
  • MW: 371.45
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-methyl-2-thiouridine

5-Methyl-2-thiouridine (2-Thio-5-methyluridine) 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: 32738-09-3
  • MF: C10H14N2O5S
  • MW: 274.29
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.63g/cm3
  • Boiling Point: N/A
  • Melting Point: 216-219 °C
  • Flash Point: N/A

4’-C-Methyl-5-methoxyuridine

4’-C-Methyl-5-methoxyuridine is a uridine analogue. 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: 2305415-71-6
  • MF: C11H16N2O7
  • MW: 288.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Aza-3’-deoxycytidine

5-Aza-3’-deoxycytidine 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: 455951-65-2
  • MF: C8H12N4O4
  • MW: 228.21
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Akt1&PKA-IN-2

Akt1&PKA-IN-2 ((R)-29) is an inhibitor of PKB/AKT with cyclin-dependent kinase 2 (CDK2) selectivity. Akt1&PKA-IN-2 inhibits AKT1, PKAa and CDK2a with IC50 values of 0.007 µM, 0.01 µM and 0.69 µM, respectively[1].

  • CAS Number: 1334108-00-7
  • MF: C20H17Cl2N3O
  • MW: 386.27
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Methoxy-1-β-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidin-6-amine

4-Methoxy-1-β-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidin-6-amine 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: 1611486-54-4
  • MF: C11H15N5O5
  • MW: 297.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.0±0.1 g/cm3
  • Boiling Point: 694.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 373.5±34.3 °C

IPI-504

Retaspimycin Hydrochloride is a potent and water-soluble inhibitor of Hsp90 with EC50s of 119 nM for both Hsp90 and Grp9.

  • CAS Number: 857402-63-2
  • MF: C31H46ClN3O8
  • MW: 624.17
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A