U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of DARINAPARSIN

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

Molecular Formula C12H22AsN3O6S
Molecular Weight 411.306
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Approval Year

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse 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: 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: 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: 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: 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: 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: 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: Page: p.4772
DLT: Ataxia, Dizziness...
Dose limiting toxicities:
Ataxia (25%)
Dizziness (25%)
Confusion (12.5%)
Fatigue (grade 2-3, 12.5%)
Sources: 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: 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: 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: Page: p.4772
AEs

AEs

AESignificanceDosePopulation
Slurred speech 25%
DLT
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: 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: Page: p.4772
Agitation grade 1, 25%
DLT
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: 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: Page: p.4772
Fever grade 1, 25%
DLT
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: 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: Page: p.4772
Trembling grade 1, 25%
DLT
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: 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: Page: p.4772
Hallucinations grade 2, 25%
DLT
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: 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: Page: p.4772
Ataxia grade 3, 50%
DLT
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: 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: Page: p.4772
Mental status changes grade 3, 50%
DLT
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: 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: Page: p.4772
Confusion 12.5%
DLT
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: 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: Page: p.4772
Ataxia 25%
DLT
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: 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: Page: p.4772
Dizziness 25%
DLT
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: 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: Page: p.4772
Fatigue grade 2-3, 12.5%
DLT
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: 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: Page: p.4772
Memory impairment grade 1, 25%
DLT
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: 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: Page: p.4772
Dizziness grade 2, 25%
DLT
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: 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: Page: p.4772
Fatigue grade 2, 25%
DLT
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: 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: Page: p.4772
Mental status changes grade 2, 25%
DLT
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: 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: Page: p.4772
PubMed

PubMed

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

Patents

Sample Use Guides

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
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:47:46 GMT 2023
Edited
by admin
on Fri Dec 15 15:47:46 GMT 2023
Record UNII
9XX54M675G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DARINAPARSIN
INN   MI   USAN   WHO-DD  
USAN   INN  
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
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
NCI_THESAURUS C274
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
FDA ORPHAN DRUG 313810
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
Code System Code Type Description
INN
8931
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
EPA CompTox
DTXSID80220108
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
MERCK INDEX
m4097
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C61490
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
PUBCHEM
11683005
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
FDA UNII
9XX54M675G
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
USAN
TT-23
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
SMS_ID
100000177149
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
DRUG BANK
DB06179
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
MESH
C515055
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
CAS
69819-86-9
Created by admin on Fri Dec 15 15:47:46 GMT 2023 , Edited by admin on Fri Dec 15 15:47:46 GMT 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY