Stereochemistry | ABSOLUTE |
Molecular Formula | C24H31N3O3.C3H6O3 |
Molecular Weight | 499.5992 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H](O)C(O)=O.CC(C)C1=CC(C(=O)N2CC3=C(C2)C=C(CN4CCN(C)CC4)C=C3)=C(O)C=C1O
InChI
InChIKey=VYRWEWHOAMGLLW-WNQIDUERSA-N
InChI=1S/C24H31N3O3.C3H6O3/c1-16(2)20-11-21(23(29)12-22(20)28)24(30)27-14-18-5-4-17(10-19(18)15-27)13-26-8-6-25(3)7-9-26;1-2(4)3(5)6/h4-5,10-12,16,28-29H,6-9,13-15H2,1-3H3;2,4H,1H3,(H,5,6)/t;2-/m.0/s1
Onalespib (AT13387; (2,4-dihydroxy-5-isopropyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl] methanone, l-lactic acid salt), is wholly owned by Astex, a novel, high-affinity HSP90 inhibitor, which is currently being clinically tested, has shown activity against a wide array of tumor cell lines, including lung cancer cell lines. As a targeted inhibitor of Hsp90, onalespib has the potential to control the proliferation of multiple solid tumors and hematological malignancies where uncontrolled cell growth is dependent on the interaction between Hsp90 and its client proteins. Astex is pursuing an approach based on the observation that addition of onalespib to a molecularly targeted agent may delay the emergence of resistance to the agent, and hence prolong the window of therapeutic benefit. Onalespib is currently being evaluated via a CRADA with the National Cancer Institute (NCI) in various tumor types, and in a Phase 1/2 clinical study in combination with AT7519, Astex CDK inhibitor.
Originator
Approval Year
AUC
Sourcing
Sample Use Guides
At 13387 (ONALESPIB) administered as a 1-hr IV infusion at a starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle.
Route of Administration:
Intravenous
AT13387 (50 nM) ONALESPIB treatment resulted in G2/M-phase arrest and significantly reduced the migration capacity. The expression of selected proteins involved in DNA repair, cell-signaling and cell growth was downregulated in vitro, though the expression of most investigated proteins recurred after 8-24 h. AT13387 induces effective cytotoxic activity in all cancer cell lines (A431, HCT116, LS174T and H314) with an IC50 < 20 nM.