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| Bortezomib (often abbreviated as BTZ) is a proteasome inhibitor that has been approved for the treatment of certain types of cancers, most notably multiple myeloma and mantle cell lymphoma. Mechanism of Action Proteasome Inhibition: Bortezomib targets the 26S proteasome, a complex responsible for degrading ubiquitinated proteins. By inhibiting the proteasome’s activity, bortezomib causes an accumulation of unwanted or misfolded proteins within the cell. Induction of Apoptosis: The buildup of these proteins leads to cellular stress and activation of the unfolded protein response (UPR). In cancer cells, which often have high levels of protein synthesis and turnover, this stress quickly tips the balance toward apoptosis (programmed cell death). Disruption of Cell Signaling Pathways: Proteasome inhibition affects several signaling pathways, including the nuclear factor-kappa B (NF-κB) pathway. NF-κB is a key regulator of cell survival, proliferation, and inflammation. Its inhibition contributes to decreased survival signals for cancer cells, enhancing the cytotoxic effects of the treatment. Bortezomib — Bortezomib is a dipeptidyl boronic acid small-molecule antineoplastic that functions as a reversible proteasome inhibitor, with highest functional relevance at the chymotrypsin-like catalytic activity of the 26S proteasome. It is a conventional cytotoxic/targeted hematologic oncology drug, marketed most prominently as Velcade, and commonly abbreviated BTZ. Clinically, it is an established systemic therapy for multiple myeloma and mantle cell lymphoma, with administration by subcutaneous or intravenous route rather than oral delivery. Its therapeutic niche is strongest in proteostasis-dependent malignancies, especially plasma-cell disorders, where high secretory load and unfolded-protein stress make malignant cells particularly vulnerable to proteasome blockade. Primary mechanisms (ranked):
Bioavailability / PK relevance: Bortezomib is not used orally in standard oncology practice because systemic delivery is by SC or IV administration. SC exposure is clinically comparable to IV for efficacy-relevant proteasome inhibition, with lower neuropathy risk. It is widely distributed, undergoes hepatic oxidative metabolism, and shows a long apparent terminal half-life after repeated dosing; hepatic impairment is more PK-relevant than renal impairment for dose adjustment. In-vitro vs systemic exposure relevance: Many mechanistic cell-culture studies use low-nanomolar to higher-nanomolar or submicromolar concentrations; the clinically relevant range is plausible for direct proteasome inhibition, but some exaggerated ROS, mitochondrial, or combination effects in vitro may require longer exposure or higher concentrations than are uniformly sustained in patients. Because bortezomib is target-engaged at the proteasome rather than simply concentration-driven bulk exposure, pharmacodynamic proteasome inhibition is more informative than plasma concentration alone. Clinical evidence status: Approved standard-of-care systemic anticancer drug with robust human evidence, including randomized phase III data and long-standing regulatory approval in multiple myeloma and mantle cell lymphoma. Evidence is strongest in hematologic malignancy regimens and weaker/inconsistent for solid tumors as single-agent therapy. Mechanistic profile
P: 0–30 min |
| Source: HalifaxProj(inhibit) |
| Type: |
| Cyclooxygenase-2 (COX-2) is an enzyme that plays a critical role in the conversion of arachidonic acid to prostaglandins, which are lipid compounds involved in various physiological processes, including inflammation, pain, and fever. COX-2 is an inducible enzyme, meaning its expression is typically low in normal tissues but can be upregulated in response to inflammatory stimuli, growth factors, and certain oncogenic signals. -Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis. -COX-2 is an inducible enzyme that is upregulated in response to pro-inflammatory signals, including cytokines (e.g., IL-1β, TNF-α) and growth factors. COX-2 is often overexpressed in various tumors, including colorectal, breast, lung, and prostate cancers. The prostaglandins produced by COX-2, particularly prostaglandin E2 (PGE2), have several effects that can facilitate cancer progression: Cell Proliferation: PGE2 can promote the proliferation of cancer cells by activating signaling pathways such as the PI3K/Akt and MAPK pathways. Nonselective NSAIDs, such as aspirin and ibuprofen, inhibit both COX-1 and COX-2. Epidemiological studies have suggested that regular use of NSAIDs may reduce the risk of certain cancers, particularly colorectal cancer. Drugs specifically targeting COX-2, such as celecoxib, have been developed. COX-2 and xanthine oxidase are ROS-producing pro-oxidant enzymes that contribute to inflammation. Elevated COX‑2 levels, often found in inflammatory conditions or certain types of cancers, can contribute to increased production of ROS. |
| 6967- | Form, | BTZ, | Formononetin Regulates Multiple Oncogenic Signaling Cascades and Enhances Sensitivity to Bortezomib in a Multiple Myeloma Mouse Model |
| - | in-vivo, | Melanoma, | U266 | - | in-vivo, | Melanoma, | RPMI-8226 |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:257 Target#:66 State#:% Dir#:1
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