KPC34: An Orally Bioavailable Next Generation Multifunctional Drug to treat Acute Leukemia Orphan Diseases

KPC34 is the first multifunctional oncology drug that combines targeted therapy with chemotherapy. KPC34 can be taken orally and has been shown in animal models to cross the blood-brain-barrier more efficiently than currently approved drugs.


Hyperthermia-induced ablation is emerging as a less invasive and more efficient A major obstacle to long-term survival of patients with acute leukemia is relapse with the emergence of chemoresistant malignant cells. Recurrent disease is especially difficult to treat in elderly patients. The emergence of drug resistant clones also limits the success of systemic chemotherapy for most solid tumors.


KPC34 is the first multifunctional drug for treating acute leukemia. It contains a deoxycytidine nucleoside and a diacylglycerol mimetic that are designed both to overcome multiple mechanisms of resistance and to provide two complementary mechanisms of action by inhibiting Protein Kinase C (PKC), which is upregulated in most patients with Acute Myelogeneous Leukemia (AML), and by inhibiting DNA synthesis.

The phospholipid modification facilitates cellular uptake independent of equilibrative nucleoside transporter 1 (ENT-1). Moreover, cleavage of the diacylglycerol mimic by cellular enzymes liberates a monophosphate form of the nucleoside, thus bypassing the need for deoxycytidine kinase (dCK) to activate the nucleoside by phosphorylation. These features address the two major modes of cancer cell resistance to AraC. Furthermore, the lipid-modified diacylglycerol mimic released from KPC34 inhibits PKC, thus providing an additional (targeted) mechanism for anti-tumor activity.

Competitive Benefits

  • High activity in vitro against human acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) cells (IC50 values in the low nanomolar range)
  • Doubling of mean survival time vs AraC in murine ALL in vivo
  • Potential use in refractory solid tumors, including pancreatic cancer
  • Potential for single-agent salvage therapy in leukemias (ALL and AML) refractory to AraC
  • Oral activity in animal models of ALL; improved pharmacokinetics vs AraC
  • Efficacy as a salvage agent in ALL resistant to AraC in mouse model
  • Treatment of symptoms of central nervous system involvement in murine ALL model

Application Fields

Hematological cancers, solid tumors, in-/out-patient care of cancer patients

Stage of Development

Studies in animal models in ALL are complete. Studies in animal models in AML are underway. GMP-ready synthetic process is developed. Batch of drug for GLP toxicology is prepared.


Greg L. Kucera, PhD
Department of Hematology & Oncology

Timothy S. Pardee, MD, PhD,
Department of Hematology & Oncology


KPC34, oncology, cancer, acute leukemia, refractory leukemia, resistance, solid tumors, phospholipid conjugate, multifunctional.


US6670341, US7026469, US7309696, US7638528, US8138200


Pardee, et al.  Blood 122 (21) November 15, 2013.
Pardee, et al. PLOS ONE 12 (6) June 23, 2017.

Licensing Contact

Peter Golikov, MBA
Licensing Director
Center for Technology Innovation & Commercialization

Reference #: 14-24

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