Onalespib (AT13387) - 10mM in DMSO , Heat shock protein HSP90 inhibitor, CAS No.912999-49-6, Heat shock protein HSP90 inhibitor

CAS: 912999-49-6 Cat. No.: O408776 Molecular Weight: 409.52

GRADE & PURITY 10mM in DMSO

Synonyms

(2,4-dihydroxy-5-isopropylphenyl)(5-((4-methylpiperazin-1-yl)methyl)isoindolin-2-yl)methanone

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

Onalespib (AT13387) Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.
In vitro

The K_d for AT13387 binding is 0.7 nM. This compares to a K_d of 6.7 nM for the binding of the ansamycin 17-AAG to the same site. The mean stoichio metry of binding for AT13387 is 1.03. The inhibition of a number of isolated kinases by AT13387 is also investigated including CDK 1, CDK 2, CDK4, FGFR3, PKB-b, JAK2, VEGFR2, PDGFRβ and Aurora B. None of the tested kinases are significantly inhibited at concentrations below 30 μM. AT13387 is a potent inhibitor of the proliferat ion and survival of many different cell lines (such as MES-SA cell line) from a variety of different tumor types. Across a panel of 30 tumor cell lines, AT13387 potently inhibits cell proliferation with GI50 values in the range 13-260 nM. AT13387 inhibits proliferation of the non-tumorigenic human prostate epithelial cell line PNT2 with a GI50 value of 480 nM.

In vivo

When given on an intermittent basis, AT13387 could be tolerated at doses of up to 70 mg/kg twice weekly or 90 mg/kg once weekly. Body weight loss in mice does not exceed 20% before recovering in all cases except one, and loss is highest following the second dose. Tumor growth inhibition is similar in NCI-H1975 for both dosing regimens. The maintenance of antitumor effects with such a prolonged off-treatment period is consistent with the extended pharmacodynamic action of AT13387 observed for mutant EGFR and other biomarkers in vitro and in vivo and the extended retention of AT13387 in tumors.
Cell Data

cell lines：B9 cells, MM cell lines

Concentrations：1 μM

Incubation Time：4 hours

Powder Purity:≥97%

Specifications

Synonyms

(2, 4-dihydroxy-5-isopropylphenyl)(5-((4-methylpiperazin-1-yl)methyl)isoindolin-2-yl)methanone

Specifications & Purity

10mM in DMSO

Biochemical and Physiological Mechanisms

Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Mechanism of action

Heat shock protein HSP90 inhibitor

Product Properties

• ALogP: 3.1

Names and Identifiers

• Isomeric SMILES: CC(C)C1=CC(=C(C=C1O)O)C(=O)N2CC3=C(C2)C=C(C=C3)CN4CCN(CC4)C
• Molecular Weight: 409.52
• Reaxy-Rn: 18536397
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=18536397&ln=

Associated Targets(Human)

HSP90B1 Tchem Endoplasmin (1 Activities)

Discover Target: HSP90B1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

HSP90AA1 Tchem Heat shock protein HSP 90-alpha (3 Activities)

Discover Target: HSP90AA1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

HSP90AB1 Tchem Heat shock protein HSP 90-beta (2 Activities)

Discover Target: HSP90AB1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro