Triapine® (CAS: 236392-56-6)

Ribonucleotide Reductase Inhibitor

cGMP API - Type II DMF (US and Canada)

Oral Capsule - Phase 1 & 2 clinical studies (NCI and Northwestern)

The figure on the right shows the docked pose of Triapine®

coordinated to the diiron cluster of RNR2 (PDB ID: 1W68)

Triapine® is s synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity being studied in the treatment of neuroendocrine tumors (NET) and glioblastoma multiforme (GBM). 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

  • NCT06410248 Triapine in Combination With Temozolomide for the Treatment of Patients With Recurrent Glioblastoma

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)

Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892). Taylor SE, Behr S, Cooper KL, Mahdi H, Fabian D, Gallion H, Ueland F, Vargo J, Orr B, Girda E, Courtney-Brooks M, Olawaiye AB, Randall LM, Richardson DL, Sullivan SA, Huang M, Christner SM, Beriwal S, Lin Y, Chauhan A, Chu E, Kohn EC, Kunos C, Ivy SP, Beumer JH. Cancer Chemother Pharmacol. 2024 Dec 14;95(1):4. doi: 10.1007/s00280-024-04720-1. PMID: 39673591 Clinical Trial.

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.