What is the difference between “DILIsym®” and “DILI-sim”?

“DILIsym” is a registered trademark for computer modeling software (DILIsym software) and for consulting services.

“DILI-sim” refers to the DILI-sim Initiative, a consortium of life science companies led by DILIsym Services, Inc., that is charged with developing the DILIsym software.

DILIsym Software
  • 1. What inputs do I need to run DILIsym for my compound?

    DILIsym facilitates predictions of hepatotoxicity based on inputs from mechanistic in vitro toxicity assays and information necessary to build PBPK models for predicting liver concentrations. The assays currently used for DILIsym inputs include transporter vesicle assays that yield IC50 and/or Ki values for a drug’s inhibition of bile acid transporters, mitochondrial assays that detail a drug’s effect on oxygen consumption rate of the in vitro cell system, and oxidative stress assays that determine a drug’s ability to initiate oxidative stress in the cell.

    DILIsym publications on tolvaptan, tolcapone/entacapone, and troglitazone showing the use of in vitro transporter, mitochondrial function, and oxidative stress data for simulations, as well as reactive metabolite focused data (methapyrilene, acetaminophen), are available.

  • 2. How is the model validated?

    In 2012, the first version of the DILIsym software was released (v1A). The released model focused on DILI mediated through the depletion of ATP levels in hepatocytes, with emphasis on oxidative stress induced by reactive metabolites. Since that time, DILIsym have evolved considerably.  DILIsym version X (DSX) was released in 2021, and includes additional DILI mechanisms related to cholestatic injury, bile acid homeostasis disruption and mitochondrial dysfunction. Resources utilized to optimize and validate the model include scientific literature, novel experiments, clinical trials and reports, expert opinions, and basic biological principles. To facilitate review of the quantitative data sets utilized to build the software, each DILIsym version includes a Data Comparisons feature that displays comparisons of simulation results with data sets used to optimize, validate, or test the model. In addition, the DILI-sim Initiative consortium routinely discusses and reviews the DILIsym Performance Review, a comprehensive assessment of software predictivity that is constantly updated. The DILIsym Performance Review has shown that DILIsym predicts the overall liver safety correctly in 80% of the use cases thus far, in addition to the investigative toxicology benefits of the software.

  • 3. On what software platform is DILIsym based?

    DILIsym version X (DSX) has been developed in C++ and released as an executable application with a graphical user interface (GUI), as well as a command-line-only option.

  • 4. Is the DILIsym software available publicly?

    The DILI-sim Initiative is currently open to new members. Please contact us for more information on joining. Through membership, corporate entities can receive access to DILIsym. Academic and non-profit researchers are also encouraged to apply for academic teaching or research licenses.

The DILI-sim Initiative