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Rimiducid | CAS No: 195514-63-7 | GMP-certified suppliers
A medication that supports advanced cellular immunotherapies by controlling graft versus host disease and aiding bone marrow transplant outcomes through targeted elimination of activated T-cells.
Therapeutic categories
Primary indications
- Investigated for use/treatment in bone marrow transplant and graft versus host disease
Product Snapshot
- Rimiducid is an investigational oral small molecule formulation
- It is primarily investigated for use in bone marrow transplant conditioning and graft versus host disease management
- The compound currently holds investigational status without full regulatory approval
Clinical Overview
Pharmacodynamically, rimiducid is employed to activate an engineered inducible caspase-9 enzyme incorporated into some chimeric antigen receptor (CAR) T-cell therapies. Upon administration, rimiducid binds selectively to a modified drug binding domain derived from human FK506-binding protein present on inducible caspase-9 constructs. This binding induces dimerization and subsequent activation of caspase-9, prompting rapid and targeted apoptosis of the modified T-cells. Clinically, this translates to a significant reduction—over 90%—in circulating alloreactive T-cells responsible for GVHD symptoms, often observed within 24 hours of treatment initiation.
The mechanism represents a safety switch system engineered to manage T-cell activity post-infusion, selectively targeting activated pathogenic T-cells while sparing non-alloreactive populations. This specificity supports immune reconstitution and may reduce adverse immune responses without broadly suppressing the immune system.
Key absorption, distribution, metabolism, and excretion (ADME) parameters have not been extensively characterized in traditional pharmacokinetic terms, as rimiducid’s action is contextually dependent on intracellular binding within modified immune cells rather than systemic receptor targeting.
Safety and toxicity considerations focus on its role in inducing apoptosis selectively in genetically modified cells. The investigational nature of rimiducid implies ongoing evaluation of its safety profile, including potential off-target effects and impacts on immune homeostasis.
Rimiducid is categorized pharmacologically as a cross-linking reagent and remains investigational without global regulatory approval. Its use is primarily within controlled gene and cell therapy protocols addressing hematological malignancies and immune complications following transplantation.
For sourcing and quality control, procurement of rimiducid APIs demands rigorous characterization of purity, stereochemistry, and batch consistency due to its specialized application in cell-based therapies. Compliance with current good manufacturing practices (cGMP) and validated analytical methodologies is essential to ensure API suitability for investigational and clinical-grade uses.
Identification & chemistry
| Generic name | Rimiducid |
|---|---|
| Molecule type | Small molecule |
| CAS | 195514-63-7 |
| UNII | H564L1W5J2 |
| DrugBank ID | DB04974 |
Pharmacology
| Summary | Rimiducid selectively binds to a modified FK506-binding protein domain on engineered inducible caspase-9 within CAR T-cells, triggering caspase-9 dimerization and activation. This mechanism induces apoptosis specifically in activated T-cells, facilitating control of graft-versus-host disease while preserving non-alloreactive immune cells. The pharmacodynamic effect results in rapid reduction of pathogenic T-cell populations to support immune system reconstitution following bone marrow transplantation. |
|---|---|
| Mechanism of action | Rimiducid binds to a drug binding domain derived from human FK506-binding protein which is present on a modified form of inducible caspase-9. This binding results in dimerization and subsequent activation of caspase-9. This system was designed to function as a "safety switch" in CAR T-cell therapy used in hematological cancers. Retroviral vectors used in production of these modified cells preferentially integrate this gene nearby promoters associated with T-cell activation. This results in higher expression of the modified inducible caspase-9 product in activated T-cells. In practice, this allows for specific targeting of these active T-cells by rimiducid which results in a decrease in circulating cell numbers of over 90% in the setting of graft versus host disease. This specificity spares non-alloreactive T-cells and allows for successful reconstitution of the transplanted immune system from these cells.[24753538] Additionally, these non-alloreactive cells retain their sensitivity to rimiducid. |
| Pharmacodynamics | Rimiducis is used to activate inducible caspase-9 produced by a modified gene included in some CAR T-cell therapies. This activation produces rapid induction of apoptosis in activated modified T-cells and resolution of the signs and symptoms of graft versus host disease within 24 hours. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Serine/threonine-protein kinase mTOR | Humans | ligand |
Formulation & handling
- Rimiducid is a small molecule with very low water solubility, suggesting challenges for oral bioavailability and formulation.
- Due to its high molecular weight and lipophilicity (LogP 10.06), lipid-based formulations or solubilizing agents may be required.
- As an investigational solid compound, Rimiducid should be stored under conditions limiting moisture and light exposure to maintain stability.
Regulatory status
Rimiducid is a type of Anticancer drugs
Anticancer drugs belong to the pharmaceutical API (Active Pharmaceutical Ingredient) category designed specifically to combat cancer cells. These powerful medications play a crucial role in cancer treatment and are developed to target and destroy cancerous cells, preventing their growth and spread.
Anticancer drugs are classified based on their mode of action and can include various types such as chemotherapy drugs, targeted therapy drugs, immunotherapy drugs, and hormonal therapy drugs. Chemotherapy drugs work by interfering with the cell division process, thereby inhibiting the growth of cancer cells. Targeted therapy drugs, on the other hand, are designed to attack specific molecules or genes involved in cancer growth, minimizing damage to healthy cells. Immunotherapy drugs stimulate the body's immune system to recognize and destroy cancer cells. Hormonal therapy drugs are used in cancers that are hormone-dependent, such as breast or prostate cancer, to block the hormones that fuel cancer cell growth.
These APIs are typically synthesized through complex chemical processes in state-of-the-art manufacturing facilities. Stringent quality control measures ensure the purity, potency, and safety of these drugs. Anticancer APIs undergo rigorous testing and adhere to stringent regulatory guidelines before being approved for clinical use.
Due to their critical role in cancer treatment, anticancer drugs are in high demand worldwide. Researchers and pharmaceutical companies continually strive to develop new and more effective APIs in this category to enhance treatment outcomes and minimize side effects. The ongoing advancements in the field of anticancer drug development offer hope for improved cancer therapies and better patient outcomes.
