Aging or Senescence implies the gradual degenerative changes that occur in the organism as we age. Aging has been with humans since the beginning of life. It is the process of loss and degeneration of the organism from its constituent substances and tissue structure to its physiological functions. The aging process occurs continuously from the fertilized egg to death, and only at a particular stage do aging characteristics become more apparent. The physiological changes in the human body’s aging process are mainly reflected in the loss of tissue cells and constituent substances, the slowing down of the body’s metabolic rate, and the decreasing function of the body and organs.
Aging is inevitable, but delaying aging is possible. Proper diet and balanced nutrition are essential to delay aging and prolong life. In addition, scientists have recently discovered a new drug, Navitoclax, which has brought us new hope in anti-aging.
What is Navitoclax?
Navitoclax is an orally active synthetic small molecule that is an antagonist of a subset of B-cell leukemia 2 (Bcl-2) family with potential antitumor activity. Navitoclax selectively binds to the apoptosis-inhibiting proteins Bcl-2, Bcl-XL, and Bcl-w, which are frequently overexpressed in various cancers, including lymphatic, breast lung, prostate, and colon cancers, and is associated with tumor resistance. Inhibition of these apoptosis inhibitors prevents their binding to the apoptotic effectors Bax and Bak proteins, thereby triggering the apoptotic process in cells overexpressing Bcl-2, Bcl-XL, and Bcl-w. This ultimately reduces the proliferation of tumor cells.
In terms of chemical structure, Navitoclax is an N-sulfonylcarboxamide consisting of 4-{4-[(4′-chloro-4,4-dimethyl-3,4,5,6-tetrahydro[biphenyl]-2-yl]methyl]piperazin-1-yl}benzoic acid with 4-{[(2R)-4-(morpholin-4-yl)-1-(phenylthio)butan-2-yl]amino}-3-[(trifluoromethyl) sulfonyl]benzenesulfonamide is formally condensed by the amino group. It is a BH3 mimetic drug that targets anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins, including BCL-2, BCL-xL, and BCL-w, and induces apoptosis in cancer cells.
As a treatment for solid tumors and hematological malignancies, it has roles as a B-cell lymphoma two inhibitor, apoptosis inducer, and antineoplastic agent. It is a member of the piperazine group, a member of the monochlorobenzene group, a member of the morphine group, an aryl sulfide, an N-sulfonyl formamide, a sulfone, an organofluorine compound, a secondary amino compound, and a tertiary amino compound.
The action of Navitoclax on organisms
Navitoclax inhibits not only Bcl-2 but also Bcl-XL and Bcl-w proteins. Since Navitoclax inhibits Bcl-XL, it reduces the lifespan of platelets, leading to thrombocytopenia, which makes it dose-limiting.
Overall, Navitoclax (ABT-263) is a potent inhibitor of Bcl-xL, Bcl-2, and Bcl-w with Ki of ≤0.5 nM, ≤1 nM, and ≤1 nM in cell-free assays but binds weakly to Mcl-1 and A1. Navitoclax is not directly related to cancer but is used as a treatment for scleroderma. Navitoclax appears to reduce existing fibrosis by inducing apoptosis of myofibroblasts.
Research directions of Navitoclax in biology
Navitoclax has been used in therapeutic and essential science trials investigating solid tumors, non-Hodgkin’s lymphoma, epidermal growth factor receptor-activating mutations, chronic lymphatic leukemia, and hematological malignancies. Navitoclax is an orally available small molecule inhibitor of Bcl-2 family proteins. It is a substance being studied for the treatment of lymphoma and other types of cancer. It blocks some of the enzymes that keep cancer cells from dying.
Scientists at Benchchem have experimentally shown that Navitoclax is an anti-aging agent that induces apoptosis in senescent cells but not in non-senescent cells. Oral administration of Navitoclax to deeply irradiated or typically aged mice reduced senescent cells, including senescent bone marrow hematopoietic stem cells and senescent muscle stem cells. This depletion attenuated premature aging of the hematopoietic system induced by total body irradiation and rejuvenated aging hematopoietic stem cells and muscle stem cells in normal-aged mice.
Summary and outlook
Navitoclax, the latest anti-aging drug discovered by scientists, has gained widespread attention in the pharmaceutical industry due to its prominent role in anti-aging. As the research progresses, the understanding of Navitoclax will become more detailed and systematic, and the application of Navitoclax in the pharmaceutical industry will become more widespread. At the same time, many experts and scholars have researched and applied Navitoclax in the anti-tumor field. It is believed that shortly, Navitoclax will shine in different fields.