Stereochemistry | ACHIRAL |
Molecular Formula | C6H10O4 |
Molecular Weight | 146.1412 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]1(CO1)[C@H](O)[C@H](O)[C@]2([H])CO2
InChI
InChIKey=AAFJXZWCNVJTMK-GUCUJZIJSA-N
InChI=1S/C6H10O4/c7-5(3-1-9-3)6(8)4-2-10-4/h3-8H,1-2H2/t3-,4+,5+,6-
Dianhydrogalactitol (VAL-083 or NSC-132313) a cytostatic sugar derivative, is alpha,omega-substituted hexitol acting as bifunctional alkylating agent. It induces interstrand crosslinks at N7 guanines leading to doublestrand breaks and HR activation independent of MGMT, and mediating cell cycle arrest through p53-dependent and p53-independent pathways. Dianhydrogalactitol is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer. The drug has not been approved for any indication outside of China. DelMar Pharmaceuticals is developing dianhydrogalactitol for the treatment of intracranial tumors.
CNS Activity
Originator
Approval Year
PubMed
Patents
Sample Use Guides
In a Phase 3 clinical trial a total of up to 180 eligible patients with recurrent/progressive patients with glioblastoma multiforme (GBM) or gliosarcoma (GS) will be randomized to receive either dianhydrogalactitol (VAL-083) or "Investigator's choice of salvage therapy" as a contemporaneous control, in a 2:1 fashion. Up to 120 eligible patients will be randomized to receive VAL-083 at 40 mg/m2 IV on days 1, 2, and 3 of a 21-day treatment-cycle, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation.
Route of Administration:
Intravenous
Treatment with 1,2:5,6-dianhydrogalactitol (DAG) (120 μmol/L) dose-dependently inhibited the proliferation and colony formation in human glioma cell lines LN229, U251, and U87MG in vitro. DAG (1, 2, 5 μmol/L) induced cell cycle arrest at G2/M phase in the 3 glioma cell lines in a dose-dependent manner.