Abstract Iso-oxazole fludelone (Iso-flu) is a 16-member ring epothilone analog obtained via total synthesis with chemical structure unrelated to Taxol® but share the mechanism of microtubule stabilization (Chou et al. PNAS 105: 13157-13162, 2008). Iso-flu is 20-fold and 1,000-fold more potent than Taxol against CCRF-CEM and CCRF-CEM/Taxol cell growth, respectively, and has the improved water solubility without using Cremophor that induces allergic reactions in human. At 1/10 therapeutic dose in nude mice, Iso-flu penetrated and accumulated in tumor tissue with over 1,000-fold IC50 concentration in tumor at 21hrs post administration, and with a tumor/brain ratio of 13. Using 6hr-i.v. infusion via tail vein, 20-30mg/kg every 12-14 days for 3-4 times, Iso-flu achieved complete tumor remission (CR) against breast MX-1, colon HCT-116, leukemia CCRF-CEM, CCRF-CEM/Taxol, ovarian SK-OV-3 xenograft tumors without any relapse for 100-200 days (or with >10-log tumor cell-kill) which is defined as the “therapeutic cure”. Remarkably, oral administration of Iso-flu 45mg/kg, Q8Dx7 also resulted in “cure” against MX-1 xenograft. Via 6hr-i.v. infusion, MX-1 tumor size as large as 7.8% of body-weight can be shrunken, disappeared and without any relapse for >150 days (i.e., “cured”). At optimal dose, schedule, and route (6hr-i.v. infusion), the therapeutic effect of Iso-flu (as indicated by the %-tumor suppression in parenthesis) for the refractor-tumors are: lung A549 (99%), neuroblastoma SK-NAS, s.c. (CR, >55 days), liver Hep (99%) [Taxol (10%)]; Pancreatic Bx PC-3 (99%) [Taxol (90%)]. For drug-resistant tumors are: CCRF-CEM/Taxol (cure), [Taxol (0%)]; lung A549/Taxol (80%) [Taxol (42%)], breast MCF-7/Adriamycin (99%) [Taxol (3.7%)]. For intracranially inoculated neuroblastoma SK-NAS, the median survival time (in days) in the Kaplan-Meier plot are: Control (16.8), BCNU (17.8), Taxol (18.8), Temodar (19.2), and Iso-flu (26.8). In conclusion, side-by-side comparison of Iso-flu with Taxol and many other cancer therapeutic agents (such as taxotere, capecitabine, gemcitabine, Temodar, cyclophosphamide, BCNU) consistently showed Iso-flu's remarkable, superior therapeutic efficacy with low toxicity as indicated by rapid recovery of the body-weight loss and devoid of neurotoxicity. The determinant factors for the extraordinary therapeutic results of Iso-flu are the unique optimal treatment conditions as indicated by slow, long infusion (e.g., 6hr or longer), the sufficient separation between doses (e.g., 14 days) and long follow-up (e.g., >100 days). It is concluded that Iso-flu is a wonder compound that warrants clinical developments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3527. doi:10.1158/1538-7445.AM2011-3527