Technology

At Culnexin Therapeutics, we are developing small molecule therapeutics against a novel target (‘oncogenic’ ubiquitin ligase), with applications in targeted/precision oncology as well as in combination therapy. The intellectual property is derived from over 20 years of research carried out at the laboratory of Dr. Pengbo Zhou, considered a leading expert on ubiquitin ligase biology at Weill Cornell Medicine, New York. Agents targeting the oncogenic ubiquitin ligase have been shown to selectively kill tumor cells, or sensitize tumor cells to cytotoxic killing by chemotherapeutic agents, and may overcome patient resistance to chemotherapeutic drugs.

Pipeline

Culnexin inhibitors are currently being investigated in the following therapeutic areas and indications.

Research & Discovery
Pre-clinical
Phase-1
Phase-2
Colorectal Cancer
Triple Negative Breast Cancer
Mesothelioma
Small Cell Lung Cancer

Publications

  • Chen, X., Zhang, Y., Douglas, L. and Zhou, P. (2001) UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. J. Biol. Chem. 276, 48175-48182.
  • Li, T., Chen, X., Garbutt, K. C., Zhou, P., and Zheng, N. (2006) Crystal Structure of DDB1 In Complex with Simian Virus 5 V Protein: Viral Hijack of A Propeller Cluster in Ubiquitin Ligase. Cell 124(1), 105-117.
  • Chen, X., Zhang, J., Lee, J., Lin, P., Ford, J. M., Zheng, N., and Zhou, P. (2006) A kinase-independent function of c-Abl in promoting proteolytic removal of UV-DDB on damaged DNA. Mol. Cell 22, 489-499.
  • Lee, J. and Zhou, P. (2007) DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Mol. Cell 26, 775-780.
  • Hannah, J. and Zhou, P. (2009) Regulation of DNA damage response pathways by the cullin-RING ubiquitin ligases. DNA Repair 8, 536-543.
  • Liu, L., Lee, S., Zhang, J., Peters, S. B., Hannah, J., Zhang, Y., Yin, Y., Koff, A., Ma, L., and Zhou, P. (2009) CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis. Mol. Cell 34, 451-460.
  • Li, W., You, L., Cooper, J., Schiavon, G., Pepe-Caprio, A., Zhou, L., Ishii, R., Giovannini, M., Hanemann, C. O., Long, S. B., Erdjument-Bromage, H., Zhou, P., Tempst, P., Giancotti, P. G. (2010) Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4DCAF1 in the nucleus. Cell 140, 477-490.
  • Lee, J. and Zhou, P. (2010) Cullins and Cancer. Genes & Cancer 1(7), 690-699.
  • Cooper, J., Li, W., You, L., Schiavon, G., Pepe-Caprio, A., Zhou, L., Ishii, R., Giovannini, M., Hanemann, C. O., Long, S. B., Erdjument-Bromage, H., Zhou, P., Tempst, P., Giancotti, F. G. (2011) Merlin/NF2 functions upstream of the nuclear E3 ubiquitin ligase CRL4DCAF1 to suppress oncogenic gene expression. Sci. Signal. 4, 6.
  • Lee, J. and Zhou, P. (2012) Pathogenic role of the CRL4 ubiquitin ligase in human disease. Front. Oncol. 2:21. doi: 10.3389/fonc.2012.00021.
  • Lee, J. and Zhou, P. (2010) Cullins and Cancer. Genes & Cancer 1(7), 690-699.
  • Cooper, J., Li, W., You, L., Schiavon, G., Pepe-Caprio, A., Zhou, L., Ishii, R., Giovannini, M., Hanemann, C. O., Long, S. B., Erdjument-Bromage, H., Zhou, P., Tempst, P., Giancotti, F. G. (2011) Merlin/NF2 functions upstream of the nuclear E3 ubiquitin ligase CRL4DCAF1 to suppress oncogenic gene expression. Sci. Signal. 4, 6.
  • Lee, J. and Zhou, P. (2012) Pathogenic role of the CRL4 ubiquitin ligase in human disease. Front. Oncol. 2:21. doi: 10.3389/fonc.2012.00021.
  • Li, W., Cooper, J., Zhou, L., Yang, C., Erdjument-Bromage, H., Zagzag, D., Snuderl, M., Ladanyi, M., Hanemann, C. O., Zhou, P., Karajannis, M., and Giancotti, F. G. (2014) CRL4DCAF1-Mediated Inhibition of Lats1/2 Promotes YAP-dependent Oncogenesis in NF2 Mutant Tumor Cells. Cancer Cell 26 (1), 48-60.
  • Wang Y, Yan F, Nasar A, Chen Z-S, Altorki NK, Stiles B, Narula N, and Zhou P. CUL4high lung adenocarcinomas are dependent on the CUL4-p21 ubiquitin signaling for proliferation and survival. Am. J. Pathol. 2021 191(9): 1638-50. PubMed PMID: 34119472; PMCID: PMC8420861.

 

Leadership Team

Culnexin Therapeutics is led by a team with expertise in world-class research, technology commercialization & drug development.

Pengbo Zhou, PhD

FOUNDER & CHAIR OF SAB

Pengbo Zhou, PhD

CHIEF EXECUTIVE OFFICER

Suman Lal, MD, PhD, MBA

William Chin, MD

BOARD DIRECTOR

William Chin, MD

Eliasof Photo

ADVISOR

Scott Eliasof, PhD

Pengbo Zhou, PhD

FOUNDING SCIENTIST & CHAIR OF SAB

Dr Pengbo Zhou is currently a Faculty Member at the Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, and is considered a world-leading expert on ubiquitin ligase biology. Research in the Zhou lab focuses on dissecting the physiological and pathological functions of ubiquitin- dependent proteolysis, and developing chemical inhibitors of ubiquitin ligases as novel therapeutic agents. The Zhou laboratory employs a combination of chemical biology, biochemistry, cell and molecular biology, mouse genetics, and human pathobiology approaches to interrogate the ubiquitin ligases as potential targets for therapeutic intervention. Dr. Zhou is also a faculty member in the Tri-Institutional (Weill Cornell Medicine, Rockefeller University and Memorial Sloan Kettering Cancer Center) PhD program in Chemical Biology.

Suman Lal, MD, PhD, MBA

CHIEF EXECUTIVE OFFICER

Dr. Suman Lal is an entrepreneur with background and interests in the area of technology commercialization. He was previously the founding CEO at DeckTherapeutics (acute omega-3 therapeutics), and Mirakel Technologies (dynamic electrochemistry-based applications in cosmetics), and co-founded Scientific Innovations, a start-up studio between Singapore and New York. Suman has an MD in clinical medicine, MSc in human genetics, and did his PhD on personalizing chemotherapy regimens in breast cancer patients based on their genetic constitution. He attended MIT as a Sloan Fellow, receiving his MBA with a focus on innovation and global leadership.

William Chin, MD

BOARD DIRECTOR

Dr. William Chin is the Bertarelli Professor of Translational Medical Science and Professor of Medicine Emeritus at Harvard Medical School (HMS). Dr. Chin is formerly EVP for Science and Regulatory Advocacy and CMO at Pharmaceutical Research and Manufacturers of America (PhRMA). He was the Executive Dean for Research at HMS and worked at Eli Lilly and Company last as Senior Vice President for Discovery Research and Clinical Investigation where he oversaw development of >130 drug candidates. Dr. Chin is a Harvard-trained endocrinologist and longstanding faculty member. He was Chief of the Genetics Division in the Department of Medicine at Brigham and Women’s Hospital, a Howard Hughes Medical Institute Investigator and Professor of Medicine at HMS. He has been honored with numerous awards for research, mentorship and leadership. Bill received his A.B. in Chemistry from Columbia University and his M.D. from HMS.

Scott Eliasof, PhD

ADVISOR

Dr. Scott Eliasof is an expert in early-stage drug development, having worked on multiple early and mid-stage drug candidates. Previously, Scott was Senior Vice President of Research at Frequency Therapeutics, a clinical stage regenerative medicine company focused on hearing loss and multiple sclerosis. Before that, Scott was Chief Scientific Officer of Cerulean Pharma, a clinical stage oncology-focused nanomedicine company, where he led all stages of research from discovery through clinical development, including platform development, discovery chemistry, analytical chemistry, DMPK, pharmacology, non-clinical toxicology and translational research. Prior to joining Cerulean, Scott was the director of the Chemical Biology Platform at the Broad Institute, directing a multi-disciplinary team of professional scientists and technicians in the fields of synthetic chemistry, analytical chemistry, high-throughput screening, computational science, and software engineering. Scott also worked as a senior scientist at Millennium Pharmaceuticals and Neurocrine Biosciences. Scott received his Ph.D. in neuroscience at UC Berkeley, and his B.S in electrical engineering at MIT.

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