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 >
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Autophagy >
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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
Neuronal Signaling >
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CDK12-IN-5

CDK12-IN-5, a pyrazolotriazine, is a potent CDK12 inhibitor with an IC50 of 23.9 nM at high ATP (2 mM). CDK12-IN-5 has no effect on CDK2/Cyclin E (IC50=173 μM) and CDK9/Cyclin T1 (IC50=127 μM) at high ATP (2 mM) (WO2021116178A1)[1].

  • CAS Number: 2651200-35-8
  • MF: C18H15F5N8O
  • MW: 454.36
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pioglitazone (potassium salt)

Pioglitazone (U 72107) potassium is an orally active and selective PPARγ (peroxisome proliferator-activated receptor) agonist with high affinity binding to the PPARγ ligand-binding domain with EC50 of 0.93 μM and 0.99 μM for human and mouse PPARγ, respectively. Pioglitazone potassium can be used in diabetes research[2][3][4].

  • CAS Number: 1266523-09-4
  • MF: C19H19KN2O3S
  • MW: 394.529
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Triapine

(E)-3-AP is the E configuration of 3-AP. 3-AP is a potent ribonucleotide reductase inhibitor. 3-AP shows anti-proliferative activity. 3-AP shows anticancer activity in L1210 leukemia model. 3-AP inhibits RR activity and DNA synthesis[1][2].

  • CAS Number: 200933-27-3
  • MF: C7H9N5S
  • MW: 195.245
  • Catalog: DNA/RNA Synthesis
  • Density: 1.46
  • Boiling Point: 436.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 217.5±31.5 °C

2’-Deoxy-2’-fluoro-3’,5’-bis-O-TBDMS-uridine

2’-Deoxy-2’-fluoro-3’,5’-bis-O-TBDMS-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: 139878-36-7
  • MF: C21H39FN2O5Si2
  • MW: 474.71
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-dimethylamino-2'-deoxyguanosine

2-Amino-2’-deoxy-N6,N6-dimethyl-2’-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: 83061-20-5
  • MF: C12H18N6O3
  • MW: 294.31
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 665.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 356.4±34.3 °C

Carbonic anhydrase inhibitor 14

Carbonic anhydrase inhibitor 14 (Compound 8b) is a carbonic anhydrase (CA) inhibitor with Ki values of 1203, 99.7, 9.4 and 27.7 nM against hCA I, hCA II, hCA IX and hCA XII, respectively. Carbonic anhydrase inhibitor 14 can also inhibit CDK2 with an IC50 of 20.3 μM. Carbonic anhydrase inhibitor 14 shows antitumor activity[1].

  • CAS Number: 2410402-75-2
  • MF: C18H17N7O2S
  • MW: 395.44
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAK-901-d3

TAK-901-d3 is the deuterium labeled TAK-901. TAK-901 is a multi-targeted aurora inhibitor with IC50s of 21 and 15 nM for aurora A and B, respectively[1][2].

  • CAS Number: 1346603-28-8
  • MF: C28H29D3N4O3S
  • MW: 507.66
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC618

CC618 is a selective peroxisome proliferator-activated receptor (PPARβ/δ) antagonist that exhibits antagonism by covalently binding to PPARβ/δ receptors[1].

  • CAS Number: 1680204-90-3
  • MF: C20H15F6N3O3S2
  • MW: 523.47
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OUL232

OUL232 is a potent inhibitor of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15. OUL232 is the most potent PARP10 inhibitor described to date (IC50=7.8 nM), as well as the first PARP12 inhibitor ever reported[1].

  • CAS Number: 943119-42-4
  • MF: C10H10N4O2S
  • MW: 250.28
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mitoxantrone-d8

Mitoxantrone-d8 (mitozantrone-d8) is the deuterium labeled Mitoxantrone. Mitoxantrone is a topoisomerase II inhibitor and also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM[1][2].

  • CAS Number: 1189974-82-0
  • MF: C22H20D8N4O6
  • MW: 452.53000
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 145 °C
  • Flash Point: N/A

Plocabulin

Plocabulin (PM060184) is a novel tubulin-binding agent binding to αβ-tubulin dimer with nanomolar affinity, inhibits a panel of 23 tumor cell lines with GI50 of 20 pM-5 nM; inhibits angiogenesis by modulation of microtubule dynamics in endothelial cells; also shows antifungal activity virtually abolishing growth of the filamentous fungus Aspergillus nidulans.

  • CAS Number: 960210-99-5
  • MF: C31H45N3O7
  • MW: 571.705
  • Catalog: Microtubule/Tubulin
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 862.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 475.4±34.3 °C

AZT triphosphate

AZT triphosphate (3'-Azido-3'-deoxythymidine-5'-triphosphate) is a active triphosphate metabolite of Zidovudine (AZT). AZT triphosphate exhibits antiretroviral activity and inhibits replication of HIV. AZT triphosphate also inhibits the DNA polymerase of HBV. AZT triphosphate activates the mitochondria-mediated apoptosis pathway[1][2][3].

  • CAS Number: 92586-35-1
  • MF: C10H16N5O13P3
  • MW: 507.18100
  • Catalog: HBV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Amino-6-chloropurine-9-(2'-O-Methyl)riboside

6-Chloro-9-(2-O-methyl-beta-D-ribofuranosyl)-9H-purin-2-amine 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: 194034-59-8
  • MF: C11H14ClN5O4
  • MW: 315.71
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bersiporocin

Bersiporocin is a prolyl-tRNA synthetase inhibitor. Bersiporocin has an IC50 of ≤100 nM for phosphoribosylpyrophosphate synthetase (PRS). Bersiporocin can be used for the research of antifibrotic[1][2].

  • CAS Number: 2241808-52-4
  • MF: C15H19Cl2N3O
  • MW: 328.24
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MLN8054

MLN8054 is a potent, selective and orally available aurora A kinase inhibitor with an IC50 of 4 nM.

  • CAS Number: 869363-13-3
  • MF: C25H15ClF2N4O2
  • MW: 476.86
  • Catalog: Aurora Kinase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 429.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 213.5±28.7 °C

ATR inhibitor 1

ATR inhibitor 1 is a ATR inhibitor extracted from patent WO2015187451A1, compound I-l, has a Ki value below 1 µΜ[1].

  • CAS Number: 1613200-51-3
  • MF: C16H12F2N8O
  • MW: 370.32
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Adenosine, 2-chloro-2'-C-Methyl-

2-Chloro-2′-β-C-methyladenosine is an adenosine analogue. Adenosine analogs mostly act as smooth muscle vasodilators and have also been shown to inhibit cancer progression. The popular products in this series are adenosine phosphate, Acadesine (HY-13417), Clofarabine (HY-A0005), Fludarabine phosphate (HY-B0028) and Vidarabine (HY-B0277)[1].

  • CAS Number: 205171-11-5
  • MF: C11H14ClN5O4
  • MW: 315.71
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.0±0.1 g/cm3
  • Boiling Point: 572.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 300.1±32.9 °C

Adenosine,2-(trifluoromethyl)- (7CI,8CI,9CI)

2-Trifluoromethyl adenosine 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: 4627-40-1
  • MF: C11H12F3N5O4
  • MW: 335.24
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.11g/cm3
  • Boiling Point: 462.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 233.4ºC

TH 588

TH588 is first-in-class nudix hydrolase family inhibitor that potently and selectively engage and inhibit the MTH1(IC50= 5 nM) in cells.IC50 value: 5 nM [1]Target: MTH1 inhibitorTH588 is highly selective towards MTH1, with no relevant inhibition of other members of the nudix protein family or a panel of 87 enzymes, GPCRs, kinases, ion channels and transporter. TH588 has been shown to selectively kill a variety of cancer cell lines and with in vivo activity shown for TH588 in SW480 colorectal and MCF7 breast tumour xenografts.

  • CAS Number: 1609960-31-7
  • MF: C13H12Cl2N4
  • MW: 295.167
  • Catalog: DNA/RNA Synthesis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 545.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 283.9±32.9 °C

Retinoic acid-d6

Retinoic acid-d6 is the deuterium labeled Retinoic acid[1]. Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha[2][3][4][5][6][7].

  • CAS Number: 2483831-72-5
  • MF: C20H22D6O2
  • MW: 306.47
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TLR7 agonist 13

TLR7 agonist 13 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: 2389988-70-7
  • MF: C17H19N5O6
  • MW: 389.36
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CP-868388 free base

CP-868388 free base is a potent, selective and orally active PPARα agonist with a Ki value of 10.8 nM. CP-868388 free base has little or no affinity for PPARβ (Ki of 3.47 μM) and PPARγ. CP-868388 free base has hypolipidemic and anti-inflammatory actions[1].

  • CAS Number: 702681-67-2
  • MF: C26H33NO5
  • MW: 439.54400
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6H-Purin-6-one,2-amino-1,9-dihydro-9-b-D-xylofuranosyl-

9-(β-D-Xylofuranosyl)guanine 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: 27462-39-1
  • MF: C10H13N5O5
  • MW: 283.24
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N2-iso-Butyroyl-5’-O-(4,4’-dimethoxytrityl)-3’-O-methylguanosine

N2-iso-Butyroyl-5’-O-(4,4’-dimethoxytrityl)-3’-O-methylguanosine 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: 103285-33-2
  • MF: C36H39N5O8
  • MW: 669.72
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rebeccamycin

Rebeccamycin, an antitumor antibiotic, inhibits DNA topoisomerase I. Rebeccamycin appears to exert its primary antineoplastic effect by poisoning topoisomerase I and has negligible effect on protein kinase C and topoisomerase II[1][2].

  • CAS Number: 93908-02-2
  • MF: C27H21Cl2N3O7
  • MW: 570.37800
  • Catalog: ADC Cytotoxin
  • Density: 1.87g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Psammaplin A

Psammaplin A, a marine metabolite, is a potent inhibitor of HDAC and DNA methyltransferases. Psammaplin A ia a highly potent and selective DAC1 inhibitor with an IC50 of 0.9 nM. Psammaplin A possess the antimicrobial effect on the Gram-positive bacteria and inhibits DNA synthesis and DNA gyrase activity. Antitumor Activity[1][2].

  • CAS Number: 110659-91-1
  • MF: C22H24Br2N4O6S2
  • MW: 664.38700
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4μ8C

4μ8C (IRE1 Inhibitor III) is a small-molecule inhibitor of IRE1α.

  • CAS Number: 14003-96-4
  • MF: C11H8O4
  • MW: 204.17900
  • Catalog: IRE1
  • Density: 1.406±0.06 g/cm3 (20 ºC 760 Torr)
  • Boiling Point: N/A
  • Melting Point: 189-190 ºC (ethanol )
  • Flash Point: N/A

Thymidine-5'-Triphosphoric Acid

Deoxythymidine-5'-triphosphate (dTTP), a deoxynucleotide, can be used in deoxyribonucleic acid synthesis[1].

  • CAS Number: 365-08-2
  • MF: C10H17N2O14P3
  • MW: 482.16800
  • Catalog: DNA/RNA Synthesis
  • Density: 1.922g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4’-Azido-3’-O-benzoyl-5’-O-(m-chlorobenzoyl)-2’-deoxy-2’-fluoro-beta-D-arabinouridine

4’-Azido-3’-O-benzoyl-5’-O-(m-chlorobenzoyl)-2’-deoxy-2’-fluoro-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: 1333126-30-9
  • MF: C23H17ClFN5O7
  • MW: 529.86
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(1-Oxopropyl)cytidine

N-(1-Oxopropyl)cytidine 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: 60107-04-2
  • MF: C12H17N3O6
  • MW: 299.28
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A