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 >
Arp2/3 Complex Dynamin Gap Junction Protein Integrin Kinesin Microtubule/Tubulin Mps1 Myosin PAK
Epigenetics >
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GPCR/G Protein >
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Membrane Transporter/Ion Channel >
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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 >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
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Vitamin D Related >
VD/VDR
Others >
Androgen Receptor Aromatase Estrogen Receptor/ERR Progesterone Receptor Thyroid Hormone Receptor Others

DMAT

DMAT is a potent and specific CK2 inhibitor with an IC50 value of 130 nM.

  • CAS Number: 749234-11-5
  • MF: C9H7Br4N3
  • MW: 476.78800
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Palmitic acid-d4-2

Palmitic acid-d4-2 is the deuterium labeled Palmitic acid. Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. PA can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells[1][2].

  • CAS Number: 75736-57-1
  • MF: C16H28D4O2
  • MW: 260.45
  • Catalog: HSP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

9-(2’-O-Acetyl-5’-O-benzoyl-3’-O-methyl-beta-D-ribofuranosyl)-2,6-dichloropurine

9-(2’-O-Acetyl-5’-O-benzoyl-3’-O-methyl-beta-D-ribofuranosyl)-2,6-dichloropurine 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: 2072145-40-3
  • MF: C20H18Cl2N4O6
  • MW: 481.29
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Merbarone

Merbarone (NSC 336628) is an orally active inhibitor of topoisomerase II. Merbarone acts primarily by blocking topoisomerase II-mediated DNA cleavage. Merbarone is an anticancer agent[1][2].

  • CAS Number: 97534-21-9
  • MF: C11H9N3O3S
  • MW: 263.27200
  • Catalog: Topoisomerase
  • Density: 1.51g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2,3,5-Tri-O-benzyl-D-ribonolactone

2,3,5-Tri-O-benzyl-D-ribono-1,4-lactone 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: 55094-52-5
  • MF: C26H26O5
  • MW: 418.48
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.21±0.1 g/cm3
  • Boiling Point: 576.8±50.0 °C
  • Melting Point: 54-55 °C
  • Flash Point: N/A

2'-Azido-2'-deoxyuridine

2'-Azido-2'-deoxyuridine (N3dUrd) is a ribonucleotide reductase inhibitor. 2'-Azido-2'-deoxyuridine has anti-cancer activity[1].

  • CAS Number: 26929-65-7
  • MF: C9H11N5O5
  • MW: 269.214
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 149-153ºC
  • Flash Point: N/A

DNA-PK-IN-7

DNA-PK-IN-7 is a potent DNA-PK inhibitor with an IC50 of 1 nM (WO2021104277A1, compound 5)[1].

  • CAS Number: 2646592-18-7
  • MF: C19H21N9O2
  • MW: 407.43
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1,3-DIMETHYLPSEUDOURIDINE

1,3-Dimethyl 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: 64272-68-0
  • MF: C11H16N2O6
  • MW: 272.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GO289

GO289 (GO-289, GO 289) is a potent and selective inhibitor of casein kinase 2 (CK2) with IC50 of 7 nM in in vitro kinase assays, shows minor effects on CKIδ and CKIα activity in vitro; GO289 showed only a moderate or minor effect on the activity of 59 kinases from a variety of classes, the second most affected kinase was PIM2 with an IC50 of 13 nM; caused dose-dependent lengthening of circadian period not only in Bmal1-dLuc reporter cells but also in Per2-dLuc reporter cells with a phase opposite to that of Bmal1-dLuc, inhibits phosphorylation of clock protein PER2 S693 in cells; strongly inhibits Caki-2, A498, and 769-P cancer cells, significantly reduces growth of mouse MLL-AF9 leukemia cells without effect on hematopoietic progenitor cells; shows effectivity on circadian period and reporter signal intensity in spleen explants of MLL-AF9 mice.

  • CAS Number: 694522-87-7
  • MF: C17H15BrN4O2S
  • MW: 419.297
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5'-ODMT cEt N-Bz A Phosphoramidite (Amidite)

5'-ODMT cEt N-Bz A Phosphoramidite Amidite is a locked nucleic acid (LNA) analogue. 5'-ODMT cEt N-Bz A Phosphoramidite Amidite possesses hybridization and mismatch discrimination attributes similar to those of LNA and shows resistance to exonuclease digestion[1].

  • CAS Number: 1197033-19-4
  • MF: C49H54N7O8P
  • MW: 899.96900
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2’-O-Methyl-5-hydroxymethyluridine

2’-O-Methyl-5-hydroxymethyluridine 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: 910050-95-2
  • MF: C11H16N2O7
  • MW: 288.25
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Herboxidiene

Herboxidiene (GEX1A) is a potent phytotoxic polyketide from Streptomyces sp. A7847 with a diverse range of activities, including herbicidal, anti-cholesterol, anti-tumor effects. Herboxidiene inhibits the pre-mRNA splicing process by binding to spliceosome-associated protein (SAP) 155, a subunit of SF3b, in the splicesome[1][2].

  • CAS Number: 142861-00-5
  • MF: C25H42O6
  • MW: 438.59700
  • Catalog: DNA/RNA Synthesis
  • Density: 1.056g/cm3
  • Boiling Point: 567.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 181.9ºC

KU-177

KU-177 is a potent inhibitor of Hsp90 ATPase homologue 1 (Aha1), ablates Aha1-driven enhancement of Hsp90-dependent tau aggregation. KU-177 also disrupts Aha1/Hsp90 interactions (IC50=4.08 μM) without inhibition of Hsp90’s ATPase activity. KU-177 can be used for tauopathies research[1][2].

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

N-(3-Chlorophenyl)-3-(1-oxo-4-phenylphthalazin-2(1H)-yl)propanamide

PARP1-IN-8 (compound 11c) is a potent and BBB-penetrated PARP1 inhibitor, with an IC50 of 97 nM. PARP1-IN-8 shows significantly potent anti-proliferative activity against Human lung adenocarcinoma epithelial cell line A549[1].

  • CAS Number: 836640-15-4
  • MF: C23H18ClN3O2
  • MW: 403.86
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY3143921

LY3143921 ((S)-Example 2) is an orally active CDC7 kinase inhibitor. LY3143921 shows broad in vitro anticancer activity[1].

  • CAS Number: 1627696-52-9
  • MF: C16H12FN5O
  • MW: 309.30
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

9-(3-Deoxy-3-fluoro-β-D-ribofuranosyl)-6-phenylpurine

9-(3-Deoxy-3-fluoro-β-D-ribofuranosyl)-6-phenylpurine 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: 1612191-91-9
  • MF:
  • MW:
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Exatecan Intermediate 7

Exatecan Intermediate 7 is the intermediate of Exatecan (HY-13631) And Exatecan (DX-8951) is a DNA topoisomerase I inhibitor with an IC50 value of 2.2 μM (0.975 μg/mL) that can be used in cancer research. Exatecan Intermediate 7 can be used to synthesize Antibody-Drug Conjugates (ADCs).

  • CAS Number: 182182-32-7
  • MF: C13H13FN2O3
  • MW: 264.25
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-(3-Phenoxybenzyl)amino-β-carboline

3-(3-Phenoxybenzyl)amino-β-carboline is a potent tubulin inhibitor. 3-(3-Phenoxybenzyl)amino-β-carboline promotes selective degradation of αβ-tubulin heterodimers. 3-(3-Phenoxybenzyl)amino-β-carboline induces G2/M phase cell cycle arrest and apoptosis. 3-(3-Phenoxybenzyl)amino-β-carboline exhibits anticancer activity[1].

  • CAS Number: 1327080-54-5
  • MF: C24H19N3O
  • MW: 365.43
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-[(1R)-1-Aminoethyl]-N-1H-pyrrolo[2,3-b]pyridin-4-ylbenzamide hydrochloride

Y-33075 hydrochloride (Y-39983) is a selective ROCK inhibitor derived from Y-27632, and is more potent than Y-27632, with an IC50 of 3.6 nM.

  • CAS Number: 471843-75-1
  • MF: C16H17ClN4O
  • MW: 316.79
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Quisinostat

Quisinostat (JNJ-26481585) is an orally available, potent HDAC inhibitor with an IC50 of 0.11 nM for HDAC1.

  • CAS Number: 875320-29-9
  • MF: C21H26N6O2
  • MW: 394.47000
  • Catalog: HDAC
  • Density: 1.358g/cm3
  • Boiling Point: 615.103ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 325.803ºC

VX-984

VX-984 (M9831) is a selective DNA-dependent protein kinase (DNA-PK) inhibitor with IC50 of 88±64 nM for A549 lung cancer cells.

  • CAS Number: 1562396-65-9
  • MF: C22H19D2N7O
  • MW: 401.46
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N6-(3-Trifluoromethylbenzyl)-2’-C-methyl adenosine

N6-(3-Trifluoromethylbenzyl)-2’-C-methyl 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: 2305415-78-3
  • MF: C19H20F3N5O4
  • MW: 439.39
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3’-O-Propargyladenosine

3’-O-Propargyladenosine 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: 2305416-10-6
  • MF: C13H15N5O4
  • MW: 305.29
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mps1-IN-2

Mps1-IN-2 is a potent, selective and ATP-competitive dual Mps1/Plk1 inhibitor, with an IC50 and a Kd of 145 nM and 12 nM for Mps1 and a Kd of 61 nM for Plk1.

  • CAS Number: 1228817-38-6
  • MF: C26H36N6O3
  • MW: 480.602
  • Catalog: Mps1
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 772.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 421.1±35.7 °C

Activity-Dependent Neuroprotective Protein Fragment 74-81, mouse, rat

Davunetide is an eight amino acid snippet derived from activity-dependent neuroprotective protein (ADNP), a neurotrophic factor that exists in the mammalian CNS. Davunetide possesses neuroprotective, neurotrophic and cognitive protective roperties. Davunetide, a microtubule-stabilizing peptide, interacts with and stabilises neuron-specific βIII-tubulin in vitro. Davunetide penetrates the blood-brain barrier and is non-toxic. Davunetide inhibits Aβ aggregation and Aβ-induced neurotoxicity[1][2][3].

  • CAS Number: 211439-12-2
  • MF: C36H60N10O12
  • MW: 824.921
  • Catalog: Microtubule/Tubulin
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1333.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 760.5±34.3 °C

Microtubule inhibitor 6

Microtubule inhibitor 6 (compound 17o) is a potent microtubule inhibitor. Microtubule inhibitor 6 shows cytotoxicity with IC50s of 14.0, 6.6, 7.0 nM for NCI-H460, BxPC-3, HT-29 cells, respectively. Microtubule inhibitor 6 efficiently inhibits microtubule polymerization[1].

  • CAS Number: 2416338-64-0
  • MF: C24H19FN2O5
  • MW: 434.42
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Casein kinase 1δ-IN-8

Casein kinase 1δ-IN-8 (compound 494) is an inhibitor of Casein kinase 1δ, Casein kinase 1δ-IN-8 can be used in the treatment of neurodegenerative disorders such as Alzheimer's disease[1].

  • CAS Number: 851396-73-1
  • MF: C19H14FN5OS
  • MW: 379.41
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Centrinone-B

Centrinone-B is a potent and highly selective PLK4 inhibitor, with a Ki of 0.59 nM.

  • CAS Number: 1798871-31-4
  • MF: C27H27F2N7O5S2
  • MW: 631.674
  • Catalog: Polo-like Kinase (PLK)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 904.9±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 501.1±37.1 °C

Deoxypodophyllotoxin

Deoxypodophyllotoxin (DPT), a derivative of podophyllotoxin, is a lignan with potent antimitotic, anti-inflammatory and antiviral properties isolated from rhizomes of Sinopodophullumhexandrum (Berberidaceae). Deoxypodophyllotoxin, targets the microtubule, has a major impact in oncology not only as anti-mitotics but also as potent inhibitors of angiogenesis[1]. Deoxypodophyllotoxin induces cell autophagy and apoptosis[2]. Deoxypodophyllotoxin evokes increase of intracellular Ca2+ concentrations in DRG neurons[3].

  • CAS Number: 19186-35-7
  • MF: C22H22O7
  • MW: 398.406
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 564.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 247.0±30.2 °C

CHIR-124

CHIR-124 is a potent and selective Chk1 inhibitor with IC50 of 0.3 nM, and also potently targets PDGFR and FLT3 with IC50s of 6.6 nM and 5.8 nM.

  • CAS Number: 405168-58-3
  • MF: C23H22ClN5O
  • MW: 419.907
  • Catalog: Checkpoint Kinase (Chk)
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A