DARINAPARSIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C12H22AsN3O6S
Molecular Weight	411.306
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[As](C)SC[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)NCC(O)=O

InChI

InChIKey=JGDXFQORBMPJGR-YUMQZZPRSA-N

InChI=1S/C12H22AsN3O6S/c1-13(2)23-6-8(11(20)15-5-10(18)19)16-9(17)4-3-7(14)12(21)22/h7-8H,3-6,14H2,1-2H3,(H,15,20)(H,16,17)(H,18,19)(H,21,22)/t7-,8-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19780704

Darinaparsin is a novel mitochondrial-targeted agent being developed for the treatment of various hematologic and solid cancers. In a Phase II study in the US, intravenous darinaparsin demonstrated evidence of clinical activity in malignant lymphoma, and in particular peripheral T-cell lymphoma (PTCL). Darinaparsin was granted Orphan Drug Designation in the US and Europe as a treatment of PTCL. The oral formulation is also being tested in Phase I for the treatment of solid tumors. Darinaparsin induces G2/M cell cycle arrest and apoptosis in tumor cells, primarily through disruption of mitochondrial functions, increased reactive oxygen species (ROS) production and modulation of signal transduction pathways.

Originator

Approval Year

Conditions

Condition	Modality	Highest Phase	Product
Multiple myeloma 159 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00423644	Primary	Phase II 1132	Unknown Approved Use Unknown
Peripheral T-cell Lymphoma 1 Sources: https://www.clinicaltrials.gov/ct2/show/NCT02653976	Primary	Phase II 1132	Unknown Approved Use Unknown
Hepatocellular carcinoma 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19565187	Primary	Phase II 1132	Unknown Approved Use Unknown
Hodgkin's lymphoma 34 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22081459	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 79 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22081459	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
588 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 588 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 588 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772	DLT: Mental status changes, Ataxia... Dose limiting toxicities: Mental status changes (grade 3, 50%) Ataxia (grade 3, 50%) Fever (grade 1, 25%) Hallucinations (grade 2, 25%) Trembling (grade 1, 25%) Agitation (grade 1, 25%) Slurred speech (25%) Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772
300 mg/m2 1 times / day multiple, intravenous MTD Dose: 300 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772	Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772
420 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 420 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 420 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772	unhealthy, ADULT n = 8 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772	DLT: Ataxia, Dizziness... Dose limiting toxicities: Ataxia (25%) Dizziness (25%) Confusion (12.5%) Fatigue (grade 2-3, 12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772
500 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 500 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 500 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772	DLT: Mental status changes, Memory impairment... Dose limiting toxicities: Mental status changes (grade 2, 25%) Memory impairment (grade 1, 25%) Dizziness (grade 2, 25%) Fatigue (grade 2, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/19584162 Page: p.4772

AEs

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00FGIJ	https://www.aablocks.com/goods/Goods/detail?id=AA00FGIJ
AK Scientific, Inc. (AKSCI)	SYN5146	http://www.aksci.com/item_detail.php?cat=SYN5146
Achemtek	0102-013510	http://www.achemtek.com/69819-86-9
Aurum Pharmatech LLC	Z-3135	http://www.Aurumpharmatech.com/Product/ProductDetails/Z_3135
BioChemPartner	BCP15637	http://www.biochempartner.com/69819-86-9-BCP15637
DC Chemicals	DC31230	http://www.dcchemicals.com//product_show-ZIO_101.html
Lab Network	LN01279348	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01279348
MolPort	MolPort-039-138-757	https://www.molport.com/shop/molecule-link/MolPort-039-138-757
MuseChem	R015179	https://www.musechem.com/product/R015179.html
Smolecule	S525038	http://www.smolecule.com/products/s525038
THE BioTek	bt-264514	https://www.thebiotek.com/product/inhibitors/bt-264514
eNovation Chemicals	D672794	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672794

PubMed

Title	Date	PubMed
A novel arsenical has antitumor activity toward As2O3-resistant and MRP1/ABCC1-overexpressing cell lines.	2008 Oct	18633430
A phase I clinical trial of darinaparsin in patients with refractory solid tumors.	2009 Jul 15	19584162
Darinaparsin induces a unique cellular response and is active in an arsenic trioxide-resistant myeloma cell line.	2009 May	19417148
Darinaparsin: solid tumor hypoxic cytotoxin and radiosensitizer.	2012 Jun 15	22535156
The novel arsenical Darinaparsin circumvents BRG1-dependent, HO-1-mediated cytoprotection in leukemic cells.	2013 Nov	23426167

Patents

Sample Use Guides

In Vivo Use Guide

In the latest clinical trial, darinaparsin was given to patients with peripheral T-cell lymphoma at a dose of 300 mg/m2 once daily for 5 consecutive days every 21 days.

Route of Administration: Intravenous

In Vitro Use Guide

Du145, PC3, and LnCap prostate cancer cells and primary prostate cells were plated at a density of 3,500 cells/200 mL in 96-well plates. 24 hours after plating, darinaparsin was added at various concentrations (from 0.001 uM to 100 uM). 72 hours after treatment, the MTS reagent was added to the cells. The color change was monitored at 490 nm and data were acquired by SOFT max pro. IC50 concentrations of Du145, PC3, and LnCap cells ranged from approximately 5 to 10 uM. Primary prostate cancer cells isolated from five different patients were equally sensitive to darinaparsin with IC50 concentrations ranging from 2.5 to 20 uM.

Name

Type

Language

DARINAPARSIN

Official Name

English

darinaparsin [INN]

Common Name

English

Darinaparsin [WHO-DD]

Common Name

English

DARINAPARSIN [JAN]

Common Name

English

GLYCINE, L-.GAMMA.-GLUTAMYL-S-(DIMETHYLARSINO)-L-CYSTEINYL-

Systematic Name

English

ZIO-101

Code

English

DARINAPARSIN [USAN]

Common Name

English

DARINAPARSIN [MI]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/11/850