Small Molecule Makes Heart Cells Out of Stem Cells

San Diego>, Calif., November 14, 2012 – Researchers at the Human BioMolecular Research Institute, Sanford-Burnham Medical Research Institute (Sanford-Burnham), and ChemRegen, Inc. have created a small molecule that convert stem cells to heart cells. Writing November 6th   in the Journal of Medicinal Chemistry, the team describes how they synthesized and tested ITD-1, a man-made, drug-like chemical that can be used to generate unlimited numbers of new heart cells from stem cells.

“Because heart disease is the leading cause of death in this country, we need to effectively replace lost heart muscle cells—called cardiomyocytes,” said Mark Mercola, Ph.D., director of Sanford-Burnham’s Muscle Development and Regeneration Program and co-author of the study. “Using a small molecule to create new heart muscle cells from stem cells is very appealing.”

Medicinal chemistry makes prototype heart drug

In an earlier study, the team screened a large collection of small molecules to find one that might one day become to a drug therapy to regenerate heart cells. Now, a team of medicinal chemists at the Human BioMolecular Research Institute, led by John Cashman, Ph.D., refined the lead compound—called ITD-1—with dynamic medicinal chemistry. They also used sophisticated enantioselective chemical synthesis to further optimize ITD-1. When added to stem cells, ITD-1 stimulates cardiomyocyte formation.

“At some point, this molecule could become the basis for a new therapeutic drug for cardiovascular disease,” explained Dennis Schade, Ph.D., a researcher in Cashman’s lab and lead author of the paper.

Mercola, Cashman, and Schade are now working with San Diego biotech company ChemRegen, Inc. to further develop ITD-1 into a therapeutic drug.

 How ITD-1 works

Stem cells are important because they do two novel things—self-renew, producing more stem cells and differentiate, becoming other cell types. To obtain a large number of a certain cell type, such as heart cells, the hard part is figuring out the cellular signals that direct them to become the desired cell type.

ITD-1 works by blocking a cellular process known as TGFβ signaling. TGFβ (transforming growth factor-b) is a protein produced by one cell type to influence others’ behaviors, such as proliferation and differentiation. TGFβ binds to a receptor on the outer surface of a responding cell to initiate an intracellular signaling cascade that causes genes to be switched on or off, ultimately altering cellular behavior—in this case making heart muscle.

ITD-1 triggers degradation of the TGFβ receptor, thus inhibiting the whole process. With TGFβ signaling turned off, stem cells are set on a course toward cardiogenesis. ITD-1 is the first selective inhibitor of TGFb, meaning that it might also have applications in many other processes controlled by TGFb.

This research was funded by the California Institute for Regenerative Medicine (grants T2-00004, RS-00169-1, RC1-000132), the National Heart, Lung, and Blood Institute of the U.S. National Institutes of Health (grants HL059502, STTR R41-HL108714), the Human BioMolecular Research Institute, the American Heart Association, the German Research Foundation, and the T Foundation.

The study was co-authored by Dennis Schade, Human BioMolecular Research Institute and ChemRegen Inc.; Marion Lanier, Human BioMolecular Research Institute and ChemRegen Inc.; Erik Willems, Sanford-Burnham and ChemRegen Inc.; Karl Okolotowicz, Human BioMolecular Research Institute; Paul J. Bushway, Sanford-Burnham; Christine Wahlquist, Sanford-Burnham; Cynthia Gilley, Human BioMolecular Research Institute; Mark Mercola, Sanford-Burnham and ChemRegen Inc., and John Cashman, Human BioMolecular Research Institute and ChemRegen Inc.

About Human BioMolecular Research Institute

The Human BioMolecular Research Institute is a <non-profit> research institute conducting basic research focused on unlocking biological and chemical principles related to diseases of the human brain, cardiovascular disease and cancer. The Institute conducts fundamental studies of central nervous system disorders, heart disease and cancer including stem cell approaches and translates findings into new drug development to address human illness. In addition, the institute promotes scientific learning through community service and public access by disseminating information and sharing research with collaborators, colleagues and the public. For more information, visit us at

About Sanford-Burnham Medical Research Institute

Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. The Institute consistently ranks among the top five organizations worldwide for its scientific impact in the fields of biology and biochemistry (defined by citations per publication) and currently ranks third in the nation in NIH funding among all laboratory-based research institutes. Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a U.S.-based, <non-profit> public benefit corporation, with operations in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, news, and events, please visit us at

About ChemRegen Inc.

ChemRegen is a for-profit company doing research directed at identifying small molecules of use for addressing human diseases. The approach is to develop regenerative medicines to work in conjunction with human embryonic stem cells to cure major human diseases including heart disease, cancer and other diseases. For more information, visit


Media contacts: To arrange on-site, phone, or Skype interviews with the researchers involved in this study, please contact John Cashman at (858) 458-9305 /