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Details

Stereochemistry ACHIRAL
Molecular Formula C24H31N3O3
Molecular Weight 409.5212
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ONALESPIB

SMILES

CC(C)C1=CC(C(=O)N2CC3=C(C2)C=C(CN4CCN(C)CC4)C=C3)=C(O)C=C1O

InChI

InChIKey=IFRGXKKQHBVPCQ-UHFFFAOYSA-N
InChI=1S/C24H31N3O3/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/h4-5,10-12,16,28-29H,6-9,13-15H2,1-3H3

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=22181674

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.7 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design.
2010 Aug 26
Patents

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.
Name Type Language
ONALESPIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
Onalespib [WHO-DD]
Common Name English
ONALESPIB [USAN]
Common Name English
ATI-13387X
Code English
ATI13387X
Code English
AT-13387
Common Name English
(2,4-DIHYDROXY-5-ISOPROPYLPHENYL)-(5-(4-METHYLPIPERAZIN-1-YLMETHYL)-1,3-DIHYDROISOINDOL-2-YL)METHANONE
Systematic Name English
onalespib [INN]
Common Name English
METHANONE, (1,3-DIHYDRO-5-((4-METHYL-1-PIPERAZINYL)METHYL)-2H-ISOINDOL-2-YL)(2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL)-
Systematic Name English
AT13387
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C74526
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Code System Code Type Description
DRUG BANK
DB06306
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INN
10031
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CAS
912999-49-6
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USAN
BC-66
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NCI_THESAURUS
C85454
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EPA CompTox
DTXSID80238485
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ChEMBL
CHEMBL1214827
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FDA UNII
Q7Y33N57ZZ
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CHEBI
140592
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PUBCHEM
11955716
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SMS_ID
100000168610
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EVMPD
SUB182117
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