OCX-0191

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H9N5S
Molecular Weight	195.245
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=S)N\N=C\C1=NC=CC=C1N

InChI

InChIKey=XMYKNCNAZKMVQN-NYYWCZLTSA-N

InChI=1S/C7H9N5S/c8-5-2-1-3-10-6(5)4-11-12-7(9)13/h1-4H,8H2,(H3,9,12,13)/b11-4+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17393073 | https://www.ncbi.nlm.nih.gov/pubmed/28421163 | https://www.ncbi.nlm.nih.gov/pubmed/19238328

Triapine (3-aminopyridine-2-carboxaldehyde thiosemcirbazone, (3-AP; NTO-1151; OCX-0191) is a novel small molecule ribonucleotide reductase inhibitor that acts on the M2 (R2) subunit. Ribonucleotide reductase is an enzyme involved in the de novo synthesis of deoxyribonucleotides, which are critical for DNA replication and DNA repair. Triapine has been used in trials phase II studying the treatment of Lung Cancer, Kidney Cancer, Prostate Cancer Pancreatic Cancer, among others. Recently was published the article describing, that the triple combination triapine-cisplatin-paclitaxel was safe and provided a rational basis for a follow-up phase II trial to evaluate the efficacy and progression-free survival in women with metastatic or recurrent uterine cervix cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ribonucleotide reductase 8 Target ID: CHEMBL3301398 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28421163	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Kidney cancer 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17393073	Primary	Phase II 1132	Unknown Approved Use Unknown
Prostate Cancer 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19082825	Primary	Phase II 1132	Unknown Approved Use Unknown
Pancreatic cancer 97 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22818416	Primary	Phase II 1132	Unknown Approved Use Unknown
Recurrent non-small cell lung cancer 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19238328	Primary	Phase II 1132	Unknown Approved Use Unknown
Uterine cervix cancer 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28421163	Primary	Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP1A2 1524 MRP1 106	CYP1A2 1054 CYP2B6 664 NAT1 2 FMO 35 MAO-B 1 NAT2 2 AO 16 MAO-A 5 XO 1 UGT 192 CYP2C8 693 CYP2A6 543 CYP2C19 991 P-gp 1537 CYP2E1 667 MRP1 107	P-gp 257

Drug as perpetrator

Target	Modality	Activity
MRP1 172	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25749419/	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25749419/	no
CYP2C19 1553	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	yes [Activation 6 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	yes [Inhibition 6 uM]
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25749419/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	major
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	minor
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	minor
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	minor
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	minor
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	minor
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	minor
AO 16	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
FMO 35	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
MAO-A 5	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
MAO-B 1	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
NAT1 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
NAT2 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
XO 1	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32989483/	no
MRP1 107	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9310341/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9310341/	yes

Sourcing

Vendor/Aggregator	ID	URL
Chemspace	CSC016285099	https://chem-space.com/CSC016285099
Enamine	BBV-87875361	http://www.enaminestore.com/catalog/BBV-87875361
NCI Plated 2007	663249

PubMed

Title	Date	PubMed
The iron-chelating drug triapine causes pronounced mitochondrial thiol redox stress.	2011 Mar 5	21195754
Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes.	2014 Oct 1	25130544

Patents

Sample Use Guides

In Vivo Use Guide

Triapine was given at a schedule of 96 mg/m2 2-h infusion daily x 4 repeated every 2 weeks in patients with recurrent renal cell carcinoma (RCC)

Route of Administration: Intravenous

In Vitro Use Guide

For in vitro evaluations, DU145 and U251 cells were exposed to 5 μmol/L and PSN1 to 3 μmol/L Triapine, concentrations that after 16 hours reduced survival by ∼50%. To evaluate the effects of Triapine on tumor cell radiosensitivity when given before irradiation, cultures were exposed to Triapine for 16 hours, irradiated, rinsed, and fed Triapine-free media, colonies were counted 10 to 12 days later and survival curves generated after normalizing for the cytotoxicity induced by Triapine alone. The exposure to Triapine before irradiation resulted in a significant increase in the radiosensitivity of each of the tumor cell lines with dose enhancement factors at a surviving fraction of 0.10 of 1.8, 1.5, and 1.6 for DU145, U251, and PSN1, respectively.

Name

Type

Language

OCX-0191

Code

English

OCX 191 [WHO-DD]

Common Name

English

3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE

Common Name

English

PAN-811

Code

English

TRIAPINE

Common Name

English

HYDRAZINECARBOTHIOAMIDE, 2-((3-AMINO-2-PYRIDINYL)METHYLENE)-

Systematic Name

English

OCX-191

Code

English

NSC-663249

Code

English

3-AP

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

588817