Hypoxia-activated prodrug

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Hypoxia-activated prodrugs are prodrugs that target regions of tumor hypoxia within tumor cells. These types of drugs have the potential, alone and in combination with conventional chemotherapy, of improving cancer therapy. It is believed that tumor hypoxia contributes significantly to treatment failure and relapse among cancer patients because cells in the hypoxic zones of solid tumors resist traditional chemotherapy for at least two reasons: first, most antitumor agents cannot penetrate beyond 50-100 micrometers from capillaries,[1] thereby never reaching those cells in the hypoxic regions. Secondly, the lower nutrient and oxygen supply to cells in the hypoxic zones of tumors cause them to divide more slowly than their well oxygenated counterparts, so hypoxic tumor cells exhibit greater resistance to chemotherapies and radiation which target rapidly dividing cells or require oxygen for efficacy.

Hypoxia also contributes to the invasive and metastatic

phenotypes of aggressive cancers by promoting genetic instability and accelerating the accumulation of mutations that can ultimately give rise to drug resistance.[2][3]

Companies working on hypoxia-activated prodrugs

Several companies worked on developing hypoxia-activated prodrugs.

Defunct or not actively working on HAPs anymore:

Actively working on it:


These companies were/are involved in developing the following drug candidates:

TH-302 (evofosfamide), CP506 and TH-4000/tarloxotinib (Convert Pharmaceuticals).[8][9]

References

  1. S2CID 42818461
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  2. S2CID 2276912
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  3. S2CID 13457619
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  4. ^ "Novacea to be acquired by Transcept Pharmaceuticals". Reuters. 2008-09-02. Retrieved 2016-03-22.
  5. ^ "Paratek Pharmaceuticals Completes Merger With Transcept Pharmaceuticals". GlobeNewswire News Room (Press release). 30 October 2014. Retrieved 2016-03-22.
  6. ^ "DEF 14A". www.sec.gov. Retrieved 2025-02-26.
  7. ^ "Convert Pharmaceuticals Home". Convert Pharmaceuticals. Retrieved 2025-01-26.
  8. ^ "Our science: Hypoxia-Activated Prodrugs". Convert Pharmaceuticals. Retrieved 2025-01-26.
  9. ^ "Tarloxotinib bromide* (TH-4000): Combining molecular targeting and hypoxia targeting in a single drug candidate". Threshold Pharmaceuticals. Archived from the original on 5 April 2016. Retrieved 24 March 2016.
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