| Bioactivity | ISA-2011B is a PIP5K1α inhibitor with promising anticancer effects . | ||||||||||||
| Invitro | The proliferation rate of PC-3 cells after treatment with ISA-2011B at 10, 20, and 50 μM is significantly reduced to 58.77%, 48.65%, and 21.62% of vehicle-treated controls, respectively. ISA-2011B exhibits the highest binding affinity to PIP5K1α, and to MAP/microtubule affinity-regulating kinase 1 and 4 (MARK1 and MARK4) across 460 kinases. ISA-2011B treatment inhibits PIP5K1α expression by 78.6% in PC-3 cells[1]. ISA-2011B leads to a remarkable reduction in AR-V7 and CDK1 in both nucleus and cytoplasm of 22Rv1 cells. ISA-2011B treatment also abolishes AR expression in the nucleus, without depleting the cytoplasmic AR[2]. | ||||||||||||
| In Vivo | ISA-2011B significantly inhibits growth of tumor cells in xenograft mice, and is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways[1]. Overexpression of AR-V7 increases PIP5K1α, promotes rapid growth of PCa in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B suppresses the growth and invasiveness of xenograft tumors overexpressing AR-V7. ISA-2011B disrupts protein stabilization of AR-V7 which is dependent on PIP5K1α, leading to suppression of invasive growth of AR-V7-high tumors in xenograft mice[2]. | ||||||||||||
| Name | ISA-2011B | ||||||||||||
| CAS | 1395347-24-6 | ||||||||||||
| Formula | C22H18ClN3O4 | ||||||||||||
| Molar Mass | 423.85 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Semenas J, et al. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3689-98. [2]. Sarwar M, et al. Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes MDV3100 resistance in prostate cancer cells. Oncotarget. 2016 Sep 27;7(39):63065-63081. |