Evofosfamide

918633-87-1

C9H16Br2N5O4P

DMSO : 94 mg/mL (209.34 mM; Need ultrasonic and warming)

Others

Evofosfamide (TH-302) is a hypoxia-activated prodrug with IC₅₀ of 10 uM and 1000 uM in hypoxia (N₂) and normoxia (21% O₂), respectively. IC50 & Target: Hypoxia-activated prodrug^[1] In Vitro: Evofosfamide (TH-302) induces gammaH2AX and apoptosis. Evofosfamide displays hypoxia-selective and concentration-dependent cytotoxic activity that is comparable in both p53-proficient and -deficient cells. Treatment with Evofosfamide (TH-302) alone causes an accumulation of G₂/M cells. Inhibition of Chk1 by PF47736 in cells treated with Evofosfamide reduces Evofosfamide (TH-302)-mediated G₂/M arrest under both normoxia and hypoxia^[1]. In Vivo: Evofosfamide (TH-302) is a hypoxia-activated prodrug known to activate selectively under the hypoxic conditions commonly found in solid tumors. The mean values of normalized K^trans decrease 69.2% for Evofosfamide (TH-302)-treated mice in Hs766t tumors, decrease 46.1% for Mia PaCa-2 tumors and increase 4.9% in SU.86.86 tumors. Both changes for Hs766t and Mia PaCa-2 treatment groups are statistically significant (P<0.01) when compare to their own control group^[2]. A significant reduction in the hypoxic fraction (HF) to 2.1%+/-4.7% is seen after 95% oxygen breathing (P<0.001), whereas 7% oxygen breathing significantly increase the HF to 29.5%+/-14.7% (P=0.029). Exposing rhabdomyosarcoma-bearing rats to increasing oxygen conditions abolish the effect of TH-302 and reduce the T4xSV from 20.4+/-3.5 to 15.3+/-2.5 days (P=0.007), whereas control animals have an increased T4xSV. Upon combination with radiotherapy, the T4xSV of TH-302-treated tumors decrease from 30.8+/-5.9 (Evofosfamide (TH-302)+radiotherapy) to 25.7+/-2.9 days (Evofosfamide (TH-302)+radiotherapy+95% O₂)^[3].