In the G1 and S phases of the cell cycle lag, tizacitabine (0.01-10 µM; 24 hours; CCRF-SB, KG-1, Jurkat, COLO-205, MCF-7, and PC-3 cells) promotes leakage resistance[1]. Tezacitabine (0.01-10 µM; 24 hours; CCRF-SB, KG-1, Jurkat, COLO-205, MCF-7, and PC-3 cells) acts concentration-dependently on apoptotic modes by inhibiting the caspase 3/7 pathway [1]. Tizacitabine possesses potent cytotoxic and cytostatic effects. Tezacitabine's cytotoxic effects include modifications in protein metabolism in addition to apoptosis [1].

In HCT 116 tumor xenografts, tizacitabine treatment (100 mg/kg; i.p.; daily; female nude mice) suppresses tumor growth [2].

Cell cycle analysis[1]
Cell Types: CCRF-SB, KG-1, Jurkat, COLO-205, MCF-7 and PC-3 Cell
Tested Concentrations: 0.01 µM, 0.1 µM, 1.0 µM and 10 µM
Incubation Duration: 24 hrs (hours)
Experimental Results: Induces leakage block in G1 (concentrations above 10 nM) and S phase (low concentrations) of the cell cycle.

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Apoptosis analysis[1]
Cell Types: CCRF-SB, KG-1, Jurkat, COLO-205, MCF-7 and PC-3 Cell
Tested Concentrations: 0.01 µM, 0.1 µM, 1.0 µM and 10 µM
Incubation Duration: 24 hrs (hours)
Experimental Results: Apoptosis was induced through the caspase 3/7 pathway in a concentration-dependent manner.

Animal/Disease Models: Female nude mice (7-9 weeks old) injected with HCT 116 cells [2]
Doses: 100 mg/kg
Route of Administration: intraperitoneal (ip) injection; daily; 14 days
Experimental Results: Inhibition of tumors in HCT 116 tumor xenografts grow.

[1]. Tezacitabine Blocks Tumor Cells in G1 and S Phases of the Cell Cycle and Induces Apoptotic Cell Death. Acta Pol Pharm. May-Jun 2005;62(3):195-205.

[2]. Tezacitabine Enhances the DNA-directed Effects of Fluoropyrimidines in Human Colon Cancer Cells and Tumor Xenografts. Biochem Pharmacol. 2007 Jan 1;73(1):44-55.

Tezacitabine is a hydroxypyrimidine.
A synthetic purine nucleoside analogue with potential antineoplastic activity.
Tezacitabine is a synthetic pyrimidine nucleoside analogue with potential antineoplastic activity. Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, further compromising DNA replication. This agent is relatively resistant to metabolic deactivation by cytidine deaminase. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates necessary for DNA synthesis and is overexpressed in many tumor types.
Tezacitabine Anhydrous is the anhydrous form of tezacitabine, a synthetic pyrimidine nucleoside analogue with potential antineoplastic activity. Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and eventually tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, thereby further inhibiting DNA replication. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates, a necessary step for DNA synthesis, and is overexpressed in many tumor cell types.

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Drug Indication
Investigated for use/treatment in colorectal cancer, lung cancer, leukemia (unspecified), and gastric cancer.

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Mechanism of Action
Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, further compromising DNA replication. This agent is relatively resistant to metabolic deactivation by cytidine deaminase. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates necessary for DNA synthesis and is overexpressed in many tumor types.

C10H11FN2O4

242.2

275.091

130306-02-4

6435808

Off-white to light yellow solid powder

590.1ºC at 760 mmHg

310.7ºC

-2.3

3

5

2

18

448

3

C1=CN(C(=O)N=C1N)[C@H]2/C(=C/F)/[C@@H]([C@H](O2)CO)O

GFFXZLZWLOBBLO-ASKVSEFXSA-N

InChI=1S/C10H12FN3O4/c11-3-5-8(16)6(4-15)18-9(5)14-2-1-7(12)13-10(14)17/h1-3,6,8-9,15-16H,4H2,(H2,12,13,17)/b5-3+/t6-,8+,9-/m1/s1

4-amino-1-[(2R,3E,4S,5R)-3-(fluoromethylidene)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one

KW 2331; FMdC; MDL 101731

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~200 mg/mL (~777.54 mM)
DMSO : ~200 mg/mL (~777.54 mM)

Solubility in Formulation 1: ≥ 5 mg/mL (19.44 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 5 mg/mL (19.44 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 5 mg/mL (19.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (388.77 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)