Business Process Reengineering and Flexibility: A Case for Unification

Business process reengineering (BPR) offers a radical approach to improving the performance of an organization. However, although there have been successes BPR is recognized as a high-risk activity, prone to failure. There are a variety of reasons for this and this paper highlights one which is argued to be the lack of attention that BPR pays to flexibility and its inability to cope with a changing environment. The purpose of this article is to raise the issue of flexibility within BPR and an approach is taken that examines flexibility in other business functional areas, such as manufacturing, architecture, information systems, and organizational strategy, where there is an extensive literature that indicates the importance of flexibility. The lessons from these other areas are identified and some of the implications for BPR are highlighted. A number of proposals are made including the suggestion that a form of “flexibility analysis” be adopted as a stage in BPR projects. It is argued that this would help to move the focus of a BPR project away from the current requirements toward a longer term, more flexible, enduring set of requirements. Flexibility analysis also ensures analysis of the kinds of changes that might be required over time, and how such change could be accommodated in the reengineered processes.     

The Applications of Flexible Manufacturing Technologies in Business Process Reengineering

Through radical redesign of business processes and systems, policies, and organizational structures, the business process reengineering (BPR) effort was initiated in the manufacturing industry to seek performance breakthroughs. This paper describes a novel approach to the BPR, which applies flexible manufacturing systems (FMSs) design and analysis technologies, such as simulation, multicriteria decision support, and artificial intelligence (AI). These technologies are integrated to design and analyze specific FMS models related to the proposed technical and managerial changes in an industrial case. First, the literature is reviewed to obtain an understanding of the BPR concept and the role of FMS design and analysis in BPR. Second, a decision-making support system is developed to illustrate how the FMS design and analysis would affect BPR. Finally, a summary of the integrated approach practice in industry and conclusions are presented. The paper shows that the key to a successful BPR approach is the identification and analysis of specific proposed models. It also demonstrates that the integrated approach enables engineers to improve the efficiency of BPR.     

Enabling BPR in Maintenance Through a Performance Measurement System Framework

With ever-increasing importance, plant maintenance is no more regarded as second line or non-productive activity. It is about time maintenance received due attention from various business improvement initiatives such as total quality management or business process reengineering (BPR). This paper builds on previous work by the authors that examines the role of performance measurement systems (PMS) in maintenance, with particular reference to developing a new PMS framework using the quality function deployment (QFD) technique. In the light of the fact that there is only limited evidence of BPR applications pertinent to equipment maintenance, this paper explores the use of the PMS framework to enable and guide sound BPR endeavors in maintenance. Condensed literature on BPR is presented followed by an outline of the PMS framework. The benefits of utilizing such a framework are examined with reference to BPR in maintenance. The practical implications of the findings are discussed based on a case study conducted in a local company.     

Creating a Fit Between BPR and IT Infrastructure: A Proposed Framework for Effective Implementation

As business imperatives change and new high-capability information technologies (IT) appear, organizations recognize the need to remain at the forefront of change by reengineering their business processes and implementing enabling responsive IT infrastructures. However, experience in this context indicates a lack of comprehension of essential elements and their mutual relationships that can contribute to the success of business-process change-implementation efforts. This article proposes a framework for managing IT for effective business-process redesign (BPR) implementation. After establishing BPR principles, components, and the relationship of BPR to some organizational and technological approaches, it presents the role and benefits of IT in BPR. The article then discusses in detail the core elements of the framework. Its theme is that an IT infrastructure that covers issues of BPR strategy development, IT strategic alignment, IT infrastructure development, IT sourcing, legacy systems reengineering, IS integration, and IS function competence is essential and critical for effective implementation.     

Minimal aerobic sludge retention time in biological phosphorus removal systems

The methodology for determination of the minimally required aerobic sludge retention time (SRTminaer) in biological phosphorus removal (BPR) systems is presented in this article. Contrary to normal biological conversions, the BPR process is not limited by a SRTmin resulting from the maximum growth rate of the organisms. This is because the aerobic SRT should be long enough to oxidize the amount of poly-hydroxy-alkanoates (PHA) stored in the anaerobic phase. This means that the SRTminaer will primarily depend on the PHA conversion kinetics and the maximal achievable PHA content in the cell (storage capacity). The model for the prediction of the minimally required aerobic SRT as a function of kinetic and process parameters was developed and compared with experimental data used to evaluate several operational aspects of BPR in a sequencing batch reactor (SBR) system. The model was proved as capable of describing them satisfactorily.Copyright 1998 John Wiley & Sons, Inc.     

Reengineering an Information System: A Case Study in Risk Reduction

Business-process reengineering (BPR), like computer information systems development (ISD), deals primarily with process and contains only weak facilities for addressing structure and culture. Manufacturing and ISD have strong roots in the functionalist traditions of natural science, and in a cultural environment their engineering stance deals poorly with obstacles to change. While the structured, or “hard,” engineering approaches have given rise to successful developments, they have not always proved effective. In ISD, the hard engineering methods have a tendency to redefine information systems problems as problems of technical development, and similarly in engineering contexts, BPR risks becoming too focused on technical processes. However, failure to gain commitment and a sense of ownership in new processes is a cause of failure in both BPR and ISD. This article explores a case study where both technical and human issues must be addressed—the extension of student record processing within a university. In this study, the BPR requirement is seen to arise from the users of the information system rather than as an imposed managerial imperative. The use of total systems intervention (TSI) and interactive planning (IP) enabled the immediate technical problems to be separated from underlying BPR requirements and from the need to gain commitment to change. Thus, unnecessary technical effort and the risks of failure from resistance to change were avoided. From the findings of this intervention, it is argued that the wider application of TSI provides a framework within which managerially perceived needs can be translated into a grassroots commitment.     

Data management in the cell therapy production facility: the batch process record (BPR)

The activities of cell therapy establishments are associated with substantial amounts of information. For reasons of best practice, regulation and adherence to prevailing standards, the data generated in the course of cell therapy product processing must be recorded and retained in an organized manner. Because cell therapy products are functionally pharmaceuticals, the paradigm of the pharmaceutical manufacturing batch process record (BPR) is proposed as a unit for collecting the data resulting from processing. Considerations for cell-processing facilities for the design of BPR and possible selection of electronic data-recording tools are reviewed, including data to collect in response to regulatory or accreditation mandates and different types of electronic data management tools that may be employed. Additionally, considerations for selection, qualification and validation of computer software for maintenance of the BPR are addressed.     

How Radical Was IT-Enabled BPR? Evidence on Financial and Business Impacts

Many large claims have been made about the payoffs that can and must be made from business process reengineering (BPR). Information technology is usually ascribed a critical role in BPR success. There is still a shortage of detailed information on the BPR phenomenon in terms of costs and results. This paper uses data from 168 UK-based organizations surveyed in the BPR heyday (1994–1996 period) to establish the size of expenditure, types of costs, and the types and size of benefits anticipated and experienced among these organizations. The majority were found to be “aiming low and hitting low,” though there was evidence of a small minority of organizations achieving something approaching what could be described as “breakthrough” results. The reasons for these results are discussed in detail and are related to the wider literature.     

Engineering the Virtual Enterprise: An Architecture-Driven Modeling Approach

The managerial and organization practices required by an increasingly dynamic competitive manufacturing, business, and industrial environment include the formation of “virtual enterprises.” A major concern in the management of virtual enterprises is the integration and coordination of business processes contributed by partner enterprises. The traditional methods of process modeling currently used for the design of business processes do not fully support the needs of the virtual enterprise. The design of these virtual enterprises imposes requirements that make it more complex than conventional intraorganizational business process design. This paper first describes an architecture that assists in the design of the virtual enterprise. Then it discusses business process reengineering (BPR) as a methodology for modeling and designing virtual organizations. While BPR presents many useful tools, the approach itself and the modeling tools commonly used for redesign have fundamental shortcomings when dealing with the virtual enterprise. However, several innovative modeling approaches provide promise for this problem. The paper discusses some of these innovative modeling approaches, such as object-oriented modeling of business processes, agent modeling of organizational players, and the use of ontological modeling to capture and manipulate knowledge about the players and processes. The paper concludes with a conceptual modeling methodology that combines these approaches under the enterprise architecture for the design of virtual enterprises.     

Comparative analysis of biological phosphate removal (BPR) and non-BPR activated sludge bacterial communities with particular reference to Acinetobacter

The bacterial community of a biological phosphate removal (BPR) activated sludge process was studied and compared to that of a non-BPR process treating the same municipal waste water. Bacterial isolates from the BPR process, as characterized by whole cell fatty acids, belonged to more than twenty genera, with Micrococcus, Staphylococcus and Acidovorax scoring highest. Acinetobacter spp represented 4% of cultured bacteria, ≤3% as estimated by fluorescence in situ hybridization, and well under 10% on the basis of the proportion of ubiquinone Q9 in the sludge. The mole proportions of ubiquinones, Q8 : Q10 : Q9 in the sludge were maintained fairly stable at approximately 9:4:1. The spectra of the isolated strains and the proportions of ubiquinones in the processes (BPR vs non-BPR) were otherwise similar, but a significant number of isolates related to actinomycetes were obtained from the BPR sludge only. The BPR process did not enrich Acinetobacter. Pure cultures of Acinetobacter isolated from the sludge stained for polyphosphate, but Acinetobacter cells responding to the ACA probe in native sludge from the BPR process did not. Instead, the bulk of the polyphosphate in the BPR sludge was located in a distinct morphotype of large, coccoid, highly clustered cells. Received 3 August 1998/ Accepted in revised form 29 October 1998     

Bacillus strains isolated from rhizosphere showed plant growth promoting and antagonistic activity against phytopathogens

Seven bacterial isolates screened from rhizosphere of common bean growing at Uttarakhand Himalaya showed potential plant growth promoting (PGP) and antagonistic activities. Based on 16S rRNA gene sequence the isolate BPR7 was identified as Bacillus sp. BPR7. The strain BPR7 produced IAA, siderophore, phytase, organic acid, ACC deaminase, cyanogens, lytic enzymes, oxalate oxidase, and solubilized various sources of organic and inorganic phosphates as well as potassium and zinc. Strain BPR7 strongly inhibited the growth of several phytopathogens such as Macrophomina phaseolina, Fusarium oxysporum, F. solani, Sclerotinia sclerotiorum, Rhizoctonia solani and Colletotricum sp. in vitro. Cell-free culture filtrate of strain BPR7 also caused colony growth inhibition of all test pathogens. PGP and antifungal activities of Bacillus sp. BPR7 suggest that it may be exploited as a potential bioinoculant agent for P. vulgaris.     

Should Deceased Donation be Morally Preferred in Uterine Transplantation Trials?

In recent years much research has been undertaken regarding the feasibility of the human uterine transplant (UTx) as a treatment for absolute uterine factor infertility (AUFI). Should it reach clinical application this procedure would allow such individuals what is often a much‐desired opportunity to become not only social mothers (via adoption or traditional surrogacy arrangements), or genetic and social mothers (through gestational surrogacy) but mothers in a social, genetic and gestational sense. Like many experimental transplantation procedures such as face, hand, corneal and larynx transplants, UTx as a therapeutic option falls firmly into the camp of the quality of life (QOL) transplant, undertaken with the aim, not to save a life, but to enrich one. However, unlike most of these novel procedures – where one would be unlikely to find a willing living donor or an ethics committee that would sanction such a donation – the organs to be transplanted in UTx are potentially available from both living and deceased donors. In this article, in the light of the recent nine‐case research trial in Sweden which used uteri obtained from living donors, and the assertions on the part of a number of other research teams currently preparing trials that they will only be using deceased donors, I explore the question of whether, in the case of UTx, there exist compelling moral reasons to prefer the use of deceased donors despite the benefits that may be associated with the use of organs obtained from the living.     

ADAM10 is expressed in human podocytes and found in urinary vesicles of patients with glomerular kidney diseases

Background

Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals.

Methods

We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle.

Results

The 50% effective inhibitory concentration (IC₅₀) of BPR1P0034 was 0.42 ± 0.11 μM, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus.

Conclusions

To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-μM) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent.     

Spectroscopic and photochemical characterization of a deep ocean proteorhodopsin

A second group of proteorhodopsin-encoding genes (blue-absorbing proteorhodopsin, BPR) differing by 20-30% in predicted primary structure from the first-discovered green-absorbing (GPR) group has been detected in picoplankton from Hawaiian deep sea water. Here we compare BPR and GPR absorption spectra, photochemical reactions, and proton transport activity. The photochemical reaction cycle of Hawaiian deep ocean BPR in cells is 10-fold slower than that of GPR with very low accumulation of a deprotonated Schiff base intermediate in cells and exhibits mechanistic differences, some of which are due to its glutamine residue rather than leucine at position 105. In contrast to GPR and other characterized microbial rhodopsins, spectral titrations of BPR indicate that a second titratable group, in addition to the retinylidene Schiff base counterion Asp-97, modulates the absorption spectrum near neutral pH. Mutant analysis confirms that Asp-97 and Glu-108 are proton acceptor and proton donor, respectively, in retinylidene Schiff base proton transfer reactions during the BPR photocycle as previously shown for GPR, but BPR contains an alternative acceptor evident in its D97N mutant, possibly the same as the second titratable group modulating the absorption spectrum. BPR, similar to GPR, carries out outward light-driven proton transport in Escherichia coli vesicles but with a reduced translocation rate attributable to its slower photocycle. In energized E. coli cells at physiological pH, the net effect of BPR photocycling is to generate proton currents dominated by a triggered proton influx, rather than efflux as observed with GPR-containing cells. Reversal of the proton current with the K+-ionophore valinomycin supports that the influx is because of voltage-gated channels in the E. coli cell membrane. These observations demonstrate diversity in photochemistry and mechanism among proteorhodopsins. Calculations of photon fluence rates at different ocean depths show that the difference in photocycle rates between GPR and BPR as well as their different absorption maxima may be explained as an adaptation to the different light intensities available in their respective marine environments. Finally, the results raise the possibility of regulatory (i.e. sensory) rather than energy harvesting functions of some members of the proteorhodopsin family.     

Different structural changes occur in blue- and green-proteorhodopsins during the primary photoreaction

We examine the structural changes during the primary photoreaction in blue-absorbing proteorhodopsin (BPR), a light-driven retinylidene proton pump, using low-temperature FTIR difference spectroscopy. Comparison of the light-induced BPR difference spectrum recorded at 80 K to that of green-absorbing proteorhodopsin (GPR) reveals that there are several differences in the BPR and GPR primary photoreactions despite the similar structure of the retinal chromophore and all-trans --> 13-cis isomerization. Strong bands near 1700 cm(-1) assigned previously to a change in hydrogen bonding of Asn230 in GPR are still present in BPR. However, additional bands in the same region are assigned on the basis of site-directed mutagenesis to changes occurring in Gln105. In the amide II region, bands are assigned on the basis of total (15)N labeling to structural changes of the protein backbone, although no such bands were previously observed for GPR. A band at 3642 cm(-1) in BPR, assigned to the OH stretching mode of a water molecule on the basis of H2(18)O substitution, appears at a different frequency than a band at 3626 cm(-1) previously assigned to a water molecule in GPR. However, the substitution of Gln105 for Leu105 in BPR leads to the appearance of both bands at 3642 and 3626 cm(-1), indicating the waters assigned in BPR and GPR exist in separate distinct locations and can coexist in the GPR-like Q105L mutant of BPR. These results indicate that there exist significant differences in the conformational changes occurring in these two types proteorhodopsin during the initial photoreaction despite their similar chromophore structures, which might reflect a different arrangement of water in the active site as well as substitution of a hydrophilic for hydrophobic residue at residue 105.     

Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity

Background

Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals.

Methods

We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle.

Results

The 50% effective inhibitory concentration (IC₅₀) of BPR1P0034 was 0.42 ± 0.11 μM, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus.

Conclusions

To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-μM) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent.     

Premature Avian Melanocyte Death Due to Low Antioxidant Levels of Protection: Fowl Model for Vitiligo

Feather melanocytes in the Barred Plymouth Rock (BPR) and White Leghorn (WL) chickens die prematurely in vivo when compared to the wild type Jungle Fowl (JF) chicken. Since these mutant melanocytes live in vitro, an environmental factor in the feather must precipitate their death. Results show that the addition of selected antioxidants, glutathione (GSH) and superoxide dismutase (SOD), can rescue these mutant melanocytes in vitro that have been placed under stress conditions that cause their premature cell death. Measurements of in vivo levels of GSH, catalase, and SOD show no significant difference in catalase activity between the JF, BPR, and WL feathers but do show a significant reduction in GSH activity in both the BPR and WL feathers to approximately 66% of the GSH concentration found in JF feathers. SOD activity in the BPR tissue is reduced significantly to approximately 50% of the JF activity and the WL SOD activity is reduced significantly to approximately 50% of the BPR SOD activity. Preliminary results of measurements of glutathione peroxidase activity indicate there is no difference in the levels of this enzyme in JF, BPR and WL feathers. A working hypothesis, based on current results, is proposed for premature cell death in BPR and WL feather melanocytes. The BPR melanocytes are genetically sensitive due to a defect in their SOD and GSH levels caused by the barring gene (B) and their death, due to reactive species of oxygen radicals, is precipitated in the poorly vascularized feather by the accumulation of oxygen radicals due to the low turnover of tissue fluids. The WL chicken carries the dominant white gene (I) in addition to the B gene. This gene directs the further reduction of the level of SOD and, when combined with the cell death mechanism already present in the BPR chicken, causes the WL feather melanocytes to die much earlier than the BPR feather melanocytes which in turn die much earlier than the wild type JF melanocytes. This same mechanistic hypothesis could apply as a cause of premature melanocyte cell death in human vitiligo wherein the vitiliginous melanocytes may have a genetic defect in their oxygen radical protection system.     

Securin enhances the anti-cancer effects of 6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole (BPR0L075) in human colorectal cancer cells

BPR0L075 [6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole] is a novel anti-microtubule drug with anti-tumor and anti-angiogenic activities in vitro and in vivo. Securin is required for genome stability, and is expressed abundantly in most cancer cells, promoting cell proliferation and tumorigenesis. In this study, we found that BPR0L075 efficiently induced cell death of HCT116 human colorectal cancer cells that have higher expression levels of securin. The cytotoxicity of BPR0L075 was attenuated in isogenic securin-null HCT116 cells. BPR0L075 induced DNA damage response, G(2)/M arrest, and activation of the spindle assembly checkpoint in HCT116 cells. Interestingly, BPR0L075 induced phosphorylation of securin. BPR0L075 withdrawal resulted in degradation of securin, mitotic exit, and mitotic catastrophe, which were attenuated in securin-null cells. Inhibition of cdc2 decreased securin phosphorylation, G(2)/M arrest and cell death induced by BPR0L075. Moreover, BPR0L075 caused cell death through a caspase-independent mechanism and activation of JNK and p38 MAPK pathways. These findings provided evidence for the first time that BPR0L075 treatment is beneficial for the treatment of human colorectal tumors with higher levels of securin. Thus, we suggest that the expression levels of securin may be a predictive factor for application in anti-cancer therapy with BPR0L075 in human cancer cells.     

Biological phosphorus removal in sequencing batch reactor with single-stage oxic process

The performance of biological phosphorus removal (BPR) in a sequencing batch reactor (SBR) with single-stage oxic process was investigated using simulated municipal wastewater. The experimental results showed that BPR could be achieved in a SBR without anaerobic phase, which was conventionally considered as a key phase for BPR. Phosphorus (P) concentration 0.22–1.79 mg L⁻¹ in effluent can be obtained after 4 h aeration when P concentration in influent was about 15–20 mg L⁻¹, the dissolved oxygen (DO) was controlled at 3 ± 0.2 mg L⁻¹ during aerobic phase and pH was maintained 7 ± 0.1, which indicated the efficiencies of P removal were achieved 90% above. Experimental results also showed that P was mainly stored in the form of intracellular storage of polyphosphate (poly-P), and about 207.235 mg phosphates have been removed by the discharge of rich-phosphorus sludge for each SBR cycle. However, the energy storage poly-β-hydroxyalkanoates (PHA) was almost kept constant at a low level (5–6 mg L⁻¹) during the process. Those results showed that phosphate could be transformed to poly-P with single-stage oxic process without PHA accumulation, and BPR could be realized in net phosphate removal.     

An Antimitotic and Antivascular Agent BPR0L075 Overcomes Multidrug Resistance and Induces Mitotic Catastrophe in Paclitaxel-Resistant Ovarian Cancer Cells

Paclitaxel plays a major role in the treatment of ovarian cancer; however, resistance to paclitaxel is frequently observed. Thus, new therapy that can overcome paclitaxel resistance will be of significant clinical importance. We evaluated antiproliferative effects of an antimitotic and antivascular agent BPR0L075 in paclitaxel-resistant ovarian cancer cells. BPR0L075 displays potent and broad-spectrum cytotoxicity at low nanomolar concentrations (IC₅₀ = 2–7 nM) against both parental ovarian cancer cells (OVCAR-3, SKOV-3, and A2780-1A9) and paclitaxel-resistant sublines (OVCAR-3-TR, SKOV-3-TR, 1A9-PTX10), regardless of the expression levels of the multidrug resistance transporter P-gp and class III β-tubulin or mutation of β-tubulin. BPR0L075 blocks cell cycle at the G2/M phase in paclitaxel-resistant cells while equal concentration of paclitaxel treatment was ineffective. BPR0L075 induces cell death by a dual mechanism in parental and paclitaxel-resistant ovarian cancer cells. In the parental cells (OVCAR-3 and SKOV-3), BPR0L075 induced apoptosis, evidenced by poly(ADP-ribose) polymerase (PARP) cleavage and DNA ladder formation. BPR0L075 induced cell death in paclitaxel-resistant ovarian cancer cells (OVCAR-3-TR and SKOV-3-TR) is primarily due to mitotic catastrophe, evidenced by formation of giant, multinucleated cells and absence of PARP cleavage. Immunoblotting analysis shows that BPR0L075 treatment induced up-regulation of cyclin B1, BubR1, MPM-2, and survivin protein levels and Bcl-XL phosphorylation in parental cells; however, in resistant cells, the endogenous expressions of BubR1 and survivin were depleted, BPR0L075 treatment failed to induce MPM-2 expression and phosphorylation of Bcl-XL. BPR0L075 induced cell death in both parental and paclitaxel-resistant ovarian cancer cells proceed through caspase-3 independent mechanisms. In conclusion, BPR0L075 displays potent cytotoxic effects in ovarian cancer cells with a potential to overcome paclitaxel resistance by bypassing efflux transporters and inducing mitotic catastrophe. BPR0L075 represents a novel microtubule therapeutic to overcome multidrug resistance and trigger alternative cell death by mitotic catastrophe in ovarian cancer cells that are apoptosis-resistant.