LP2, a stable lanthipeptide derived from cAng-(1-7), exerts myeloprotective action in mice

Area of Science:

• Hematology
• Pharmacology
• Oncology

Background:

• Linear unstable angiotensins are known to stimulate hematopoiesis.
• The myeloprotective and stability profiles of cyclic angiotensin-(1-7) and its derivatives require further investigation.

Purpose of the Study:

• To evaluate the myeloprotective capacity of cyclic angiotensin-(1-7) in mice.
• To assess the stability of cyclic angiotensin-(1-7) in rats.
• To determine if LP2, a modified cyclic angiotensin-(1-7), offers myeloprotection in tumor-bearing mice.

Main Methods:

• Cyclic angiotensin-(1-7) efficacy was tested in gemcitabine-treated mice for blood cell restoration.
• Stability of cyclic angiotensin-(1-7) was assessed in rat blood post-administration.
• LP2's ability to restore bone marrow cells after 5-fluorouracil treatment and counter anemia in erlotinib-treated tumor-bearing mice was measured.

Main Results:

• Cyclic angiotensin-(1-7) dose-dependently restored platelet levels but had limited effect on white blood cells.
• In vivo studies revealed breakdown of cyclic angiotensin-(1-7) into cyclic angiotensin-(2-7) and (3-7).
• LP2 significantly restored bone marrow cell counts and countered anemia in preclinical models.

Conclusions:

• LP2 demonstrates significant myeloprotective action.
• The findings support the continued clinical development of LP2 for hematological support.