Mechanism of Action: Multidrug and Toxin Extrusion Transporter 1 Inhibitors

Drugs with Mechanism of Action: Multidrug and Toxin Extrusion Transporter 1 Inhibitors

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Gilead Sciences Inc	TYBOST	cobicistat	TABLET;ORAL	203094-001	Sep 24, 2014		RX	Yes	Yes	8,148,374*PED				Y
Gilead Sciences Inc	TYBOST	cobicistat	TABLET;ORAL	203094-001	Sep 24, 2014		RX	Yes	Yes	10,039,718*PED				Y
Gilead Sciences Inc	TYBOST	cobicistat	TABLET;ORAL	203094-001	Sep 24, 2014		RX	Yes	Yes
Viiv Hlthcare	TRIUMEQ	abacavir sulfate; dolutegravir sodium; lamivudine	TABLET;ORAL	205551-001	Aug 22, 2014		RX	Yes	Yes	9,242,986*PED				Y
Viiv Hlthcare	TRIUMEQ	abacavir sulfate; dolutegravir sodium; lamivudine	TABLET;ORAL	205551-001	Aug 22, 2014		RX	Yes	Yes

Multidrug and Toxin Extrusion Transporter 1 Inhibitors Market Analysis and Financial Projection

The market dynamics and patent landscape for Multidrug and Toxin Extrusion Transporter 1 (MATE1/SLC47A1) inhibitors reflect a growing focus on drug safety, pharmacokinetic optimization, and therapeutic innovation. Here's an analysis of key developments:

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Market Dynamics

1. Clinical Relevance and Regulatory Drivers

   • MATE1 inhibitors are critical in managing drug-drug interactions (DDIs), particularly for cationic drugs like metformin and chemotherapeutics such as oxaliplatin[3][16]. Regulatory agencies now recommend MATE1 interaction studies during preclinical trials, spurring demand for in vitro testing kits (e.g., ReadyCell’s PreadyTake-MATE1)[10].
   • Over 30 drugs are identified as MATE1 substrates or inhibitors[3], with tyrosine kinase inhibitors (TKIs) like nilotinib and imatinib showing potent non-competitive inhibition, raising concerns about unintended DDIs in cancer treatment[5][17].

2. Emerging Therapeutic Opportunities

   • Recent studies highlight MATE1’s role in glioma stem cell viability, where its inhibition enhances temozolomide efficacy[14]. This positions MATE1 as a potential target for glioblastoma therapy.
   • Selective MATE1 inhibitors like prazosin and granisetron are being explored for clinical utility, though challenges remain in achieving specificity over related transporters (e.g., OCT2)[3][7].

3. Competitive Landscape

   • Roche dominates biologics patent filings (e.g., HER2 inhibitors)[2], but MATE1-focused innovation is led by academic consortia and biotech firms. For example, computational QSAR models and combinatorial pharmacophore approaches are enabling high-throughput inhibitor discovery[1][7][16].
   • Over 900 prescription drugs have been screened for MATE1 inhibition, with 84 identified as potential inhibitors, including FDA-approved drugs like cimetidine[3][7].

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Patent Landscape

Key Innovations and Holders

Patent Focus	Examples	Key Players
Screening Methods	HEK293/MDCKII cells overexpressing MATE1 for in vitro DDI assays[10]	ReadyCell, academic institutions
Computational Models	QSAR and machine learning models predicting MATE1 inhibition[1][16]	University research teams, pharma R&D
Therapeutic Inhibitors	Tyrosine kinase inhibitors (e.g., nilotinib) with dual MATE1/OCT2 inhibition[5][17]	Novartis, academic-industry collaborations
Biological Sequence Analysis	HER2 mAbs with optimized CDR regions for enhanced binding[2]	Roche, Sun Yat-sen University

Trends and Challenges

• Growth in ADC and Cell Therapy Patents: While HER2 biologics dominate, MATE1 patents focus on small molecules and transporter modulation[2][6].
• Species-Specific Challenges: Mouse MATE1 shows 100-fold lower sensitivity to inhibitors like nilotinib than human MATE1, complicating preclinical studies[17].
• Litigation Risks: 28% of drug products with active patents face generic competition despite exclusivity[15], emphasizing the need for robust patent strategies around novel mechanisms.

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Strategic Implications

• R&D Prioritization: Computational tools like ECFP4 fingerprints and MM–GB/SA scoring are reducing reliance on wet-lab screening[1][16].
• Regulatory Compliance: MATE1 is now prioritized in FDA/EMA DDI guidelines, necessitating early-stage transporter studies[10][16].
• Market Entry Barriers: Dominance of established players like Roche in biologics contrasts with fragmented small-molecule innovation, creating opportunities for niche developers[2][7].

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"The field of HER2 biologics is dominated by Roche with 1092 patent applications, but MATE1 inhibitor patents reflect a shift toward transporter-mediated drug optimization." [2][7]

As MATE1's role in drug disposition becomes clearer, the intersection of computational modeling, targeted therapy, and regulatory compliance will define its commercial trajectory.

References

1. https://pubs.acs.org/doi/10.1021/acs.jcim.4c00921
2. https://sklqrcm.um.edu.mo/202308301n/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC4068829/
4. https://go.drugbank.com/articles/A18359
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC8707461/
6. https://patents.google.com/patent/WO2021000855A1/en
7. https://pubs.acs.org/doi/10.1021/jm301302s
8. https://pmc.ncbi.nlm.nih.gov/articles/PMC11464068/
9. https://www.danubia.com/who-we-are/mate-molnar/
10. https://readycell.com/preadytake-mate1-screening-renal-drug-interactions/
11. https://patents.google.com/patent/WO2014184265A1/en
12. https://patents.justia.com/inventor/mate-hidvegi
13. https://www.mdpi.com/1422-0067/22/12/6439
14. https://pmc.ncbi.nlm.nih.gov/articles/PMC10560943/
15. https://www.fdli.org/wp-content/uploads/2022/08/7-Darrow-and-Mai.pdf
16. https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65eeac0a66c1381729b9206e/original/prediction-of-inhibitory-activity-against-the-mate1-transporter-via-combined-fingerprint-and-physics-based-machine-learning-models.pdf
17. https://www.mdpi.com/1999-4923/13/12/2004

Last updated: 2025-03-23