ONALESPIB

Investigational

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 Search

SMILES

CC(C)C1=C(O)C=C(O)C(=C1)C(=O)N2CC3=CC=C(CN4CCN(C)CC4)C=C3C2

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

Molecular Formula	C24H31N3O3
Molecular Weight	409.5212
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://astx.com/research-development/clinical-pipeline/onalespib-at13387-hsp90-inhibitor-solid-tumors/
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Heat shock protein HSP90 35 Target ID: CHEMBL2095165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22181674	Inhibitor 8504		0.7 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Prostate cancer 186 Sources: https://clinicaltrials.gov/ct2/show/NCT01685268	Primary		Phase II 1147	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: https://clinicaltrials.gov/ct2/show/NCT02535338	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
3790 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25336693/	310 mg/m² 1 times / week multiple, intravenous dose: 310 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
923 ng/mL EXPERIMENT https://www.dfhcc.harvard.edu/fileadmin/media/ETCTN/02_Developing_an_ETCTN_Study/PTMA_Requests/AT13387_03Feb2014.pdf	180 mg/m² single, intravenous dose: 180 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1790 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25336693	260 mg/m² 1 times / week multiple, intravenous dose: 260 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
7293 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25336693/	310 mg/m² 1 times / week multiple, intravenous dose: 310 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2376 ng × h/mL EXPERIMENT https://www.dfhcc.harvard.edu/fileadmin/media/ETCTN/02_Developing_an_ETCTN_Study/PTMA_Requests/AT13387_03Feb2014.pdf	180 mg/m² single, intravenous dose: 180 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
4905 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25336693	260 mg/m² 1 times / week multiple, intravenous dose: 260 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25336693/	310 mg/m² 1 times / week multiple, intravenous dose: 310 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7 h EXPERIMENT https://www.dfhcc.harvard.edu/fileadmin/media/ETCTN/02_Developing_an_ETCTN_Study/PTMA_Requests/AT13387_03Feb2014.pdf	180 mg/m² single, intravenous dose: 180 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
6.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25336693	260 mg/m² 1 times / week multiple, intravenous dose: 260 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ONALESPIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
16.3% EXPERIMENT https://www.dfhcc.harvard.edu/fileadmin/media/ETCTN/02_Developing_an_ETCTN_Study/PTMA_Requests/AT13387_03Feb2014.pdf	unknown		ONALESPIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34065	https://www.001chemical.com/chem/search?q=DY34065
001 Chemical	DY34066	https://www.001chemical.com/chem/search?q=DY34066
1PlusChem LLC	1P00GUHQ	https://www.1pchem.com/search?query=1P00GUHQ
AK Scientific	2232AH	https://aksci.com/item_detail.php?cat=2232AH
Angene	AGN-PC-0VS14J	http://www.angenechemical.com/productshow/AGN-PC-0VS14J.html
ApexBio Technology	A4056	https://www.apexbt.com/catalogsearch/result/?q=A4056
AstaTech	31408	http://astatechinc.com/CPSResult.php?CRNO=31408
BOC Sciences	912999-49-6	http://www.bocsci.com/description.asp?cas=912999-49-6
Cayman Chemical	10655	http://www.caymanchem.com/app/template/Product.vm/catalog/10655
ChemShuttle	141356	https://www.chemshuttle.com/catalogsearch/result/?q=141356
eMolecules	271447150	https://orderbb.emolecules.com/search/#?query=271447150
eMolecules	43366944	https://orderbb.emolecules.com/search/#?query=43366944
eNovation Chemicals	D501850	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501850&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A1798	http://www.excenen.com/searchresultlist.php?id=EX-A1798
KeyOrganics	AS-74503	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74503
mcule	MCULE-8215335849	https://mcule.com/MCULE-8215335849/
MedChem Express	HY-14463	https://www.medchemexpress.com/search.html?q=HY-14463&ft=&fa=&fp=
Molcore	MC34065	http://www.molcore.com/CatMC34065.html
Molcore	MC34066	http://www.molcore.com/CatMC34066.html
Molnova	M16557	https://www.molnova.com/en/serch-list.html?keywords=M16557
MolPort	MolPort-023-219-182	https://www.molport.com/shop/molecule-link/MolPort-023-219-182
MuseChem	I005444	https://www.musechem.com/product/I005444.html
MuseChem	I008450	https://www.musechem.com/product/I008450.html
ShangHai Biochempartner	BCP03601	http://www.biochempartner.com/search_BCP03601
TargetMol	T6284	https://www.targetmol.com/search?keyword=T6284

PubMed

Title	Date	PubMed
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.	2010-08-26	20662534

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:03:31 GMT 2025` Edited by `admin` on `Mon Mar 31 19:03:31 GMT 2025`
Record UNII	Q7Y33N57ZZ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ONALESPIB

Official Name

English

onalespib [INN]

Preferred 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

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