Triapine® (CAS: 236392-56-6)
Ribonucleotide Reductase Inhibitor
cGMP API - Type II DMF (US and Canada)
Oral Capsule - Phase 1 & 2 clinical studies (NCI)
Triapine® is s synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity being studied in the treatment of cancer. It is a type of ribonucleotide reductase inhibitor. Also called 3-aminopyridine-2-carboxaldehyde thiosemicarbazone and 3-AP, Triapine® inhibits the enzyme ribonucleotide reductase, resulting in the inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleotides necessary for DNA synthesis.
Clinical Studies (Active)
NCT04494113 Testing the Response to the Anti-cancer Drug, Triapine, in Uterine Cancers Using Markers From the Tissue at the Time of Hysterectomy
NCT04234568 Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors
NCT02595879 Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vaginal Cancer
NCT02466971 Testing the Addition of a New Anti-Cancer Drug, Triapine, to the Usual Chemotherapy Treatment (Cisplatin) During Radiation Therapy for Advanced-stage Cervical and Vaginal Cancers
NCT05724108 Testing the Effectiveness of an Anti-cancer Drug, Triapine, When Used With Targeted Radiation-based Treatment (Lutetium Lu 177 Dotatate), Compared to Lutetium Lu 177 Dotatate Alone for Metastatic Neuroendocrine Tumors
Clinical Studies (Completed)
NCT00075504 Triapine and Gemcitabine Hydrochloride in Gallbladder Cancer
NCT00390052 3-AP in Treating Patients With Advanced or Metastatic Solid Tumors
NCT00335998 Phase I Study of Intravenous Triapine (IND # 68338) in Combination With Pelvic Radiation Therapy With or Without Weekly Intravenous Cisplatin Chemotherapy for Locally Advanced Cervical, Vaginal, or Pelvic Gynecologic Malignancies
NCT00293345 3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma
NCT00085371 Triapine as First-Line or Second-Line Therapy in Treating Patients With Locally Advanced or Metastatic Cancer of the Pancreas
NCT00288093 3-AP and Radiation Therapy in Treating Patients With Stage III Pancreatic Cancer That Cannot Be Removed By Surgery
NCT00077350 A Phase II Trial of Triapine (NSC #663249) in Combination With Gemcitabine as Second Line Treatment of Non-Small Cell Lung Cancer
NCT00077181 3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies
NCT00941070 Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer
NCT00077545 3-AP Plus Cisplatin in Treating Patients With Recurrent or Metastatic Adenocarcinoma of the Esophagus or Gastroesophageal Junction
NCT00095888 3-AP and Gemcitabine in Treating Patients With Refractory Metastatic Breast Cancer
NCT00081276 3-AP and Cisplatin in Treating Patients With Recurrent or Persistent Platinum-Resistant Ovarian Epithelial or Primary Peritoneal Cancer
NCT00079014 3-AP and Doxorubicin In Treating Patients With Metastatic or Refractory Solid Tumors
NCT00084877 Irinotecan and 3-AP in Treating Patients With Metastatic or Unresectable Solid Tumors
NCT00381550 3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia
NCT00078975 3-AP and Gemcitabine in Treating Patients With Recurrent, Unresectable, or Metastatic Pancreatic Cancer
NCT00075660 3-AP in Treating Patients With Previously Untreated Locally Recurrent or Metastatic Renal Cell Carcinoma
NCT00006218 3-AP in Treating Patients With Advanced Cancer
NCT00054015 3-AP in Treating Patients With Advanced Prostate Cancer
NCT00064090 3-AP and Cytarabine in Treating Patients With Hematologic Cancer
NCT00064051 3-AP and Gemcitabine in Treating Patients With Unresectable or Metastatic Pancreatic Cancer
NCT00064064 3-AP and Gemcitabine in Treating Patients With Metastatic Non-Small Cell Lung Cancer
NCT00077558 3-AP Followed By Fludarabine In Treating Patients With Relapsed or Refractory Acute or Chronic Leukemia or High-Risk Myelodysplastic Syndrome
NCT00077415 3-AP and Gemcitabine as Second-Line Therapy in Treating Patients With Stage III or Stage IV Recurrent Non-Small Cell Lung Cancer
NCT00004213 3-Aminopyridine-2-carboxaldehyde Thiosemicarbazone in Treating Patients With Solid Tumors
NCT00016874 3-AP Plus Cisplatin and Paclitaxel in Treating Patients With Advanced or Metastatic Cancer
NCT00024323 Combination Chemotherapy in Treating Patients With Advanced Cancer
Intellectual Property
Nanopharmaceutics holds world-wide exclusive rights to U.S. patents 5,869,676 and related foreign filings. A new composition-of-matter patent is in preparation.
References (over 160 total)
Ribonucleotide reductase regulatory subunit M2 drives glioblastoma TMZ resistance through modulation of dNTP production. Ella N Perrault, Jack M Shireman, Eunus S Ali, Peiyu Lin, Isabelle Preddy, Cheol Park, Shreya Budhiraja, Shivani Baisiwala, Karan Dixit, C David James, Dieter H Heiland, Issam Ben-Sahra, Sebastian Pott, Anindita Basu, Jason Miska, Atique U Ahmed. Sci Adv. 2023 May 19;9(20):eade7236. doi: 10.1126/sciadv.ade7236. Epub 2023 May 17. PMID: 37196077.
Co-administration of Inulin and Iron Fortificants improves Iron Deficiency Biomarkers in Female Sprague Dawley Rats. Rizwan Ahmad AM, Farooq U, Anees M, Anis RA, Rashid S, Ahmed W. Food Sci Nutr. 2022 May 7;10(7):2141-2148. doi: 10.1002/fsn3.2337. eCollection 2022 Jul. PMID: 35844906.
Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present. Huff SE, Winter JM, Dealwis CG. Biomolecules. 2022 Jun 10;12(6):815. doi: 10.3390/biom12060815. PMID: 35740940.
Replication stress induced by the ribonucleotide reductase inhibitor guanazole, triapine and gemcitabine in fission yeast. Alyahya MY, Khan S, Bhadra S, Samuel RE, Xu YJ. FEMS Yeast Res. 2022 Mar 24;22(1):foac014. doi: 10.1093/femsyr/foac014. PMID: 35262697.
Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine. Timoshnikov VA, Selyutina OY, Polyakov NE, Didichenko V, Kontoghiorghes GJ. Int J Mol Sci. 2022 Jan 23;23(3):1247. doi: 10.3390/ijms23031247. PMID: 35163169.