Darinaparsin

DRACPC ID  DRACPC0034

Active Ingredients   Darinaparsin

Description  A small-molecule organic arsenical with potential antineoplastic activity. Although the exact mechanism of action is unclear, darinaparsin, a highly toxic metabolic intermediate of inorganic arsenicals (iAs) that occurs in vivo, appears to generate volatile cytotoxic arsenic compounds when glutathione (GSH) concentrations are low. The arsenic compounds generated from darinaparsin disrupt mitochondrial bioenergetics, producing reactive oxygen species (ROS) and inducing ROS-mediated tumor cell apoptosis; in addition, this agent or its byproducts may initiate cell death by interrupting the G2/M phase of the cell cycle and may exhibit antiangiogenic effects. Compared to inorganic arsenic compounds such as arsenic trioxide (As2O3), darinaparsin appears to exhibit a wide therapeutic window.

Synonyms  DMAIII(SG); S-Dimethylarsino-Glutathione; ZIO-101; Darinaparsin

Type  Small Molecule

Disease  Cancer/Tumor

Classification

  

Peptide and derivative

Structure Information


Molecular Formula  C12H22AsN3O6S

Molecular Weight  411.31

Active Sequence  XXG

Sequence Length  3

Modification  X(1)=gGlu, X(2)=Cys(Unk)

Structure

 

Show IUPAC/InChI/SMILES

IUPAC Name  (2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-dimethylarsanylsulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid

InChI  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

InChI_Key JGDXFQORBMPJGR-YUMQZZPRSA-N

SMILES  O=C(O)[C@@H](N)CCC(N[C@@H](CS[As](C)C)C(NCC(O)=O)=O)=O

External Codes


PubChem CID  11683005

DrugBank Accession Number  DB06179

NCI Thesaurus Code  C61490  

UNII  9XX54M675G   GSRS

CAS  69819-86-9



Drug approval


Drug indication
    Investigated for use/treatment in blood (blood forming organ disorders, unspecified), cancer/tumors (unspecified), solid tumors, multiple myeloma, and liver cancer.

    The drug is not approved.

ClinicalTrials.gov Identifier Title Condition or disease Phase Purpose
NCT01139359 A Phase I Dose Escalation Study of Darinaparsin in Combination With CHOP in Previously Untreated Patients With Lymphomas Who Are Scheduled to Receive CHOP Alone Lymphoma Phase 1 Treatment
NCT01139346 Phase I Study of Oral Darinaparsin in Advanced Solid Tumors Advanced Solid Tumors Phase 1 Treatment
NCT00421213 Phase II Study of ZIO-101 in Advanced Blood and Bone Marrow Cancers Hematologic Neoplasms; Bone Marrow Neoplasms; Non-Hodgkin's Lymphoma Phase 2 Treatment
NCT00423306 A Phase-II Trial of ZIO 101 in Advanced Hepatocellular Carcinoma Hepatocellular Carcinoma Phase 2 Treatment
NCT00509782 Phase I Trial of ZIO-101 in Patients With Solid Tumors Solid Tumors Phase 1 Treatment

    More clinical information is obtained from ClinicalTrials.gov.





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