Mipsagargin (G-202) | CAS No. 1245732-48-2

Description

Product Description

Mipsagargin (CAS No. 1245732-48-2), also known as G-202, represents an innovative approach to targeted cancer therapy research. It is a proagent that leverages the potency of Thapsigargin, a highly cytotoxic natural product, but controls its activity through tumor-selective activation. The molecule is constructed by coupling a prostate-specific membrane antigen (PSMA)-targeting peptide with an analog of Thapsigargin that inhibits the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump. This design enables selective delivery of cytotoxic activity to tumor cells expressing PSMA, while minimizing systemic toxicity.

Targeted Proagent Concept

The fundamental concept behind Mipsagargin is “tumor-selective activation.” Thapsigargin itself is an extremely potent inhibitor of calcium homeostasis within cells, leading to endoplasmic reticulum stress and apoptosis. However, its nonspecific activity precludes systemic administration. By masking its cytotoxic core with a peptide substrate that can be cleaved specifically by PSMA, researchers have created a compound that remains inert in circulation but becomes activated in the tumor microenvironment.

Tumor Relevance and Research Applications

PSMA is overexpressed in prostate cancer and in the vasculature of many solid tumors, including kidney, bladder, brain, and certain breast cancers. This broad tumor association makes Mipsagargin a valuable tool for preclinical and translational research in oncology, particularly in advanced or refractory disease models where conventional agents may fail.

Scientific Significance

Mipsagargin illustrates a new generation of proagents that use enzymatic activation within the tumor microenvironment to trigger cytotoxicity. The strategy of conjugating a potent natural product inhibitor with a tumor-selective activation mechanism is of significant interest for scientists exploring precision oncology, targeted prodrug design, and novel cancer therapeutics.

Product Specifications

• CAS Number: 1245732-48-2

• Product Name: Mipsagargin (G-202)

• Synonyms: G-202, Thapsigargin proagent, PSMA-activated thapsigargin analog

• Molecular Formula: C___H___N___O___ (exact formula available upon request)

• Molecular Weight: Available upon request

• Appearance: White to off-white solid (research grade)

• Purity: ≥ 98% (HPLC)

• Solubility: Soluble in DMSO, ethanol; limited aqueous solubility

• Storage: Store at -20°C, protected from light and moisture

• Stability: Stable under recommended storage conditions

• Applications: Research use only; not for human or veterinary use

Extended Technical Overview

The specifications of Mipsagargin highlight its role as a precision oncology research tool. With a well-defined peptide masking domain and a potent thapsigargin analog payload, its chemical stability and selective activation are crucial for preclinical studies. Researchers benefit from its consistent quality, enabling reproducibility in in vitro and in vivo tumor models.

Mechanism of Action & Research Applications

Mipsagargin works through a dual-component mechanism:

1. Masking with a PSMA-specific peptide – This ensures the compound remains inactive in circulation, reducing off-target toxicity.

2. Enzymatic cleavage at tumor sites – PSMA-expressing tumor cells or neovasculature cleave the masking peptide, releasing the active thapsigargin analog.

3. SERCA pump inhibition – The activated analog blocks SERCA, disrupting calcium homeostasis in the endoplasmic reticulum.

4. Apoptosis induction – Calcium dysregulation triggers ER stress, unfolded protein response, and programmed cell death.

Research Relevance

Mipsagargin has been studied in the context of:

• Prostate cancer research – Due to high PSMA expression.

• Solid tumor vasculature studies – Since PSMA is expressed in endothelial cells of tumor-associated vasculature.

• Drug resistance models – As a potential tool to overcome chemotherapy resistance by targeting calcium signaling pathways.

• Combination strategies – Mipsagargin may be combined with other therapeutic research agents to investigate synergistic antitumor effects.

Broader Implications

Mipsagargin represents a new paradigm of tumor-activated cytotoxic agents. Its modular design could inspire the development of other enzyme-activated prodrugs for oncology, expanding the arsenal of precision research tools for difficult-to-treat cancers.

Side Effects (For Research Reference)

In research models, Mipsagargin exhibits unique side effect profiles due to its mechanism:

• Selective Toxicity: Unlike conventional chemotherapy, systemic toxicity is minimized due to peptide masking.

• Potential Off-Target Activity: Residual activity may occur in tissues with low-level PSMA expression.

• Calcium Homeostasis Disruption: Activation leads to ER stress and cell death, which, while desirable in tumor cells, may affect non-target cells if specificity is incomplete.

• Model Observations: In preclinical studies, hepatotoxicity, fatigue-like behavior, and transient vascular effects have been noted.

Importance for Research

Understanding the side effect spectrum of Mipsagargin is crucial for translational research. Side effect profiles guide dosing strategies, toxicity monitoring, and the design of safer analogs.

Guidance

All information is for research purposes only. Mipsagargin is not approved for therapeutic or clinical use. Proper laboratory safety and CMGP (Customized Manufacturing Good Practice) handling standards are required.

Disclaimer

For research use only. Not for human or veterinary use. Handle under appropriate laboratory safety and CMGP standards.

Keywords

Mipsagargin G-202, CAS 1245732-48-2, Thapsigargin proagent, PSMA-targeted prodrug, SERCA inhibitor oncology research, tumor-selective cytotoxicity, precision cancer research compound, apoptosis via calcium signaling.CGMP peptide supply.