{
    "title": "NOSH-Aspirin vs Cancer",
    "inventor_name": "Khosrow Kashfi",
    "publication_year": 2012,
    "device_name": "NOSH-Aspirin",
    "goal": "Treat and shrink tumors of various cancers while reducing side-effects compared with conventional aspirin.",
    "problem_addressed": "Cancer treatment efficacy and toxicity of long-term aspirin use (ulcers, kidney failure, bleeding).",
    "concept_summary": "NOSH-Aspirin is a hybrid aspirin derivative that simultaneously releases nitric oxide (NO) and hydrogen sulfide (H_2S). The NO moiety protects gastric mucosa, while the H_2S moiety enhances anti-cancer activity. The compound shows dramatically higher potency than aspirin alone in vitro and reduces tumor growth in mice without observable toxicity.",
    "detailed_description": "The invention describes synthesis of four NOSH compounds (NOSH-1 to NOSH-4) by coupling aspirin with a nitrate-based NO-donor and an H_2S-donor (e.g., ADT-OH, TBZ, lipoic acid). In cell-culture assays across 11 human cancer lines, the most potent, NOSH-1, exhibited an IC_5_0 of ~48 nM in HT-29 colon cancer cells and caused 85 % tumor-cell shrinkage in mouse xenograft models. Toxicity assays (LDH release) showed no damage to normal cells. The drug is intended for oral administration at lower doses than aspirin, aiming to provide anti-inflammatory and chemopreventive effects with minimal gastrointestinal toxicity.",
    "category": "Medical & Dental Technologies",
    "principles": [
        "Hybrid drug design",
        "Nitric oxide release",
        "Hydrogen sulfide release",
        "Anti-inflammatory action",
        "Antineoplastic activity"
    ],
    "scientific_domains": [
        "Pharmacology",
        "Medicinal Chemistry",
        "Oncology"
    ],
    "mechanisms_of_action": [
        "Release of NO to protect gastric lining",
        "Release of H_2S to induce cancer-cell apoptosis",
        "Inhibition of cyclooxygenase pathways",
        "Modulation of cell-growth signaling"
    ],
    "materials": [
        "Aspirin (acetylsalicylic acid)",
        "Nitrooxy group (NO donor)",
        "5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH, H_2S donor)",
        "4-hydroxy-thiobenzamide (TBZ, H_2S donor)",
        "Lipoic acid (H_2S donor)",
        "Salicylaldehyde",
        "Succinic anhydride",
        "Dicyclohexylcarbodiimide (DCC)",
        "4-Dimethylaminopyridine (DMAP)",
        "Silver nitrate (AgNO_3)",
        "Potassium permanganate (KMnO_4)",
        "Dichloromethane (solvent)",
        "Acetone"
    ],
    "energy_sources": [],
    "inputs": [
        "Oral dose of NOSH-Aspirin compound",
        "Patient (human or animal) body"
    ],
    "outputs": [
        "Reduced tumor size",
        "Cancer-cell apoptosis",
        "Anti-inflammatory effect",
        "Minimal gastrointestinal toxicity"
    ],
    "claimed_performance": "In mice, NOSH-Aspirin reduced tumor growth by up to 85 % and showed 100 000- to 250 000-fold greater potency than aspirin in vitro; IC_5_0 of 48 +/- 3 nM in colon-cancer cells; no observable toxicity in animal studies.",
    "experimental_evidence": "Mouse xenograft studies showed tumor shrinkage without toxicity; in-vitro assays on 11 human cancer cell lines demonstrated nanomolar IC_5_0 values; LDH release assays indicated lack of cytotoxicity to normal cells.",
    "replication_status": null,
    "keywords": [
        "NOSH-Aspirin",
        "Nitric oxide donor",
        "Hydrogen sulfide donor",
        "Hybrid NSAID",
        "Cancer chemoprevention",
        "Anti-inflammatory",
        "Aspirin derivative"
    ],
    "related_technologies": [
        "NO-NSAIDs",
        "HS-NSAIDs",
        "Traditional aspirin",
        "Coxibs"
    ],
    "controversy_level": "low",
    "confidence_score": 0.9,
    "practicability_score": 0.8,
    "fringe_score": 0.2,
    "evidence_strength": 0.6,
    "risk_score": 0.3,
    "trl_estimate": 4,
    "source_urls": [
        "http://www.express.co.uk/posts/view/307217/New-aspirin-fights-cancer",
        "http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/ml300002m"
    ],
    "organizations": [
        "Sophie Davis School of Biomedical Education, City College of New York",
        "American Association for Cancer Research"
    ],
    "applications": [
        "Cancer therapy (adjuvant or primary)",
        "Anti-inflammatory medication with reduced GI toxicity"
    ],
    "limitations": [
        "Data limited to in-vitro and animal models",
        "Human safety and efficacy not yet demonstrated",
        "Potential unknown metabolic interactions"
    ],
    "open_questions": [
        "Will the potency translate to humans?",
        "What are the pharmacokinetics and long-term safety profile?",
        "Can the compound be manufactured at scale cost-effectively?"
    ],
    "red_flags": [],
    "evidence_quotes": [
        "In tests on mice, it has been shown to shrink cancer cells by 85 per cent.",
        "Only 24 hours after treating a culture of cancer cells, the NOSH aspirin demonstrated 100,000 times greater potency than aspirin alone.",
        "NOSH-1 was the most potent, with an IC50 of 48 +/- 3 nM in HT-29 colon cancer cells.",
        "The compound caused cancer cells to self-destruct, inhibited the proliferation of the cells and significantly reduced tumour growth without any signs of toxicity.",
        "Writing in the journal ACS Medicinal Chemistry Letters, Professor Kashfi said any working therapy for humans was still years away."
    ]
}