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TAS-114

Cat. No. M14781
TAS-114 Structure
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Biological Activity

TAS-114 is a dual dUTPase/dihydropyrimidine dehydrogenase (DPD) inhibitor, can improving the therapeutic efficacy of fluoropyrimidine.

Chemical Information
Molecular Weight 451.54
CAS Number 1198221-21-4
Solubility (25°C) DMSO 90 mg/mL
Storage 2-8°C, sealed
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Hikari Araki, et al. A semimechanistic population pharmacokinetic and pharmacodynamic model incorporating autoinduction for the dose justification of TAS-114

[2] Akihito Kawazoe, et al. A multicenter phase II study of TAS-114 in combination with S-1 in patients with pretreated advanced gastric cancer (EPOC1604)

[3] Nobuyuki Yamamoto, et al. A randomized, phase 2 study of deoxyuridine triphosphatase inhibitor, TAS-114, in combination with S-1 versus S-1 alone in patients with advanced non-small-cell lung cancer

[4] Toshihiko Doi, et al. First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors

[5] Wakako Yano, et al. TAS-114, a First-in-Class Dual dUTPase/DPD Inhibitor, Demonstrates Potential to Improve Therapeutic Efficacy of Fluoropyrimidine-Based Chemotherapy

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