336113-53-2 Usage
Description
Ispinesib is a potent and highly specific small-molecule inhibitor of kinesin-like spindle protein (KSP), which plays a crucial role in the formation of bipolar spindles during mitosis in both normal and tumor cells. It is an anticancer agent that has been tested for the treatment of human diseases.
Uses
Used in Anticancer Applications:
Ispinesib is used as an anticancer agent for its ability to inhibit the motor protein Eg5 (kinesin-5), which is essential for establishing a bipolar spindle during mitosis in both normal and tumor cells. By inhibiting Eg5, Ispinesib induces a monopolar spindle phenotype, leading to the activation of a spindle assembly checkpoint, mitotic arrest, and subsequent cell death. This makes it effective against various types of cancer, including colon, pancreas, prostate, and lung cancer cells in vitro.
Additionally, Ispinesib is used to halt the growth of treatment-resistant glioblastoma tumor-initiating cells, preventing tumor initiation and self-renewal of a cancer stem cell population. It is also effective in reducing glioma cell invasion.
Used in Preclinical Studies:
Ispinesib is used in preclinical studies for its potential to produce tumor regression in breast cancer cell xenografts in mice at a dosage of 10 mg/kg. This application helps researchers understand the drug's effectiveness and potential side effects before moving on to clinical trials.
Biological Activity
ispinesib (sb-715992) is a selective inhibitor of ksp with ic50 value of 0.5 nm [1].kinesin spindle protein (ksp) is a kinesin motor protein and plays an important role in the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. it has been shown that abnormal expression of ksp is correlated with a variety of human cancers and its inhibitors may be a promising anticancer agent [2] [3].ispinesib (sb-715992) is a potent ksp inhibitor and often combines with chemotherapy drugs to tumor treatment. when tested with a panel of 23 tumor cell lines, ispinesib (sb-715992) treatment showed high activity to inhibit ksp in most of the cell lines while only rh18 having an ic50 value greater than 1 μm (median ic50=4.1 nm, maximum ic50=0.5 nm) by using pptp method [1]. in a panel of 53 breast cell lines, ispinesib (sb-715992) exhibits broad antiproliferative activity and up-regulated the expression of both mitotic and apoptotic markers in mda-mb-468 cell line [2]. when tested with pc-3 cells, ispinesib (sb-715992) treatment inhibits cell proliferation, inducs cell apoptosis and up-regulated the expressions of genes that related to the control of cell proliferation, cell cycle, cell signaling pathways and apoptosis [3].in mouse model with 26 tumor cells subcutaneous xenograft, administration of ispinesib (sb-715992) inducs markedly tumor growth delay with the percent of 88% (23/26) and maintained completed response (cr) in the rhaboid tumor, wilms tumor and ewing sarcoma xenograft mouse model [1].
references
[1]. carol, h., et al., initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program. pediatr blood cancer, 2009. 53(7): p. 1255-63.[2]. purcell, j.w., et al., activity of the kinesin spindle protein inhibitor ispinesib (sb-715992) in models of breast cancer. clin cancer res, 2010. 16(2): p. 566-76.[3]. davis, d.a., et al., increased therapeutic potential of an experimental anti-mitotic inhibitor sb715992 by genistein in pc-3 human prostate cancer cell line. bmc cancer, 2006. 6: p. 22.
Check Digit Verification of cas no
The CAS Registry Mumber 336113-53-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,3,6,1,1 and 3 respectively; the second part has 2 digits, 5 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 336113-53:
(8*3)+(7*3)+(6*6)+(5*1)+(4*1)+(3*3)+(2*5)+(1*3)=112
112 % 10 = 2
So 336113-53-2 is a valid CAS Registry Number.
InChI:InChI=1/C30H33ClN4O2/c1-20(2)27(34(17-7-16-32)29(36)23-12-10-21(3)11-13-23)28-33-26-18-24(31)14-15-25(26)30(37)35(28)19-22-8-5-4-6-9-22/h4-6,8-15,18,20,27H,7,16-17,19,32H2,1-3H3/t27-/m1/s1
336113-53-2Relevant articles and documents
Fluorinated quinazolinones as potential radiotracers for imaging kinesin spindle protein expression
Holland, Jason P.,Jones, Michael W.,Cohrs, Susan,Schibli, Roger,Fischer, Eliane
supporting information, p. 496 - 507 (2013/03/13)
Anti-mitotic anti-cancer drugs offer a potential platform for developing new radiotracers for imaging proliferation markers associated with the mitosis-phase of the cell-cycle. One interesting target is kinesin spindle protein (KSP) - an ATP-dependent motor protein that plays a vital role in bipolar spindle formation. In this work we synthesised a range of new fluorinated-quinazolinone compounds based on the structure of the clinical candidate KSP inhibitor, ispinesib, and investigated their properties in vitro as potential anti-mitotic agents targeting KSP expression. Anti-proliferation (MTT and BrdU) assays combined with additional studies including fluorescence-assisted cell sorting (FACS) analysis of cell-cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Additional studies using confocal fluorescence microscopy showed that these compounds induce M-phase arrest via monoaster spindle formation. Structural studies revealed that compound 20-(R) is the most potent fluorinated-quinazolinone inhibitor of KSP and represents a suitable lead candidate for further studies on designing 18F-radiolabelled agents for positron-emission tomography (PET).
