AT13387

Modify Date: 2024-01-09 19:09:42

AT13387 structure	Common Name	AT13387
	CAS Number	912999-49-6	Molecular Weight	409.521
	Density	1.2±0.1 g/cm3	Boiling Point	605.7±55.0 °C at 760 mmHg
	Molecular Formula	C₂₄H₃₁N₃O₃	Melting Point	N/A
	MSDS	N/A	Flash Point	320.1±31.5 °C

Use of AT13387

Onalespib (AT13387) is a potent inhibitor of Hsp90, with a Kd of 0.71 nM.

Name	(2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone
Synonym	More Synonyms

Description	Onalespib (AT13387) is a potent inhibitor of Hsp90, with a Kd of 0.71 nM.
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> HSP Signaling Pathways >> Metabolic Enzyme/Protease >> HSP Research Areas >> Cancer
Target	HSP90:0.71 nM (Kd)
In Vitro	Onalespib (Compound 35) is a potent inhibitor of Hsp90, with Kd of 0.71 nM. Onalespib shows potent antiproliferative activity in HCT116 cells, with an IC50 of 31 nM. Onalespib also strongly inhibits the proliferation of a panel of human tumor cell lines, showing IC50 of < 100 nM[1]. Onalespib exhibits cytotoxic activity against many of the PPTP cell lines, with median IC50 of 41 nM[2].
In Vivo	Onalespib (60 mg/kg, ip 3 days on and 3 days off for four cycles) shows antitumor activity in nude BALB/c mice bearing early stage HCT116 human colon carcinoma xenografts[1]. Onalespib (40 or 60 mg/kg, i.p.) induces significant differences in EFS distribution compared to controls in 17% evaluable solid tumor xenografts, but in none of the ALL xenografts[2].
Cell Assay	In vitro testing is performed using DIMSCAN. Cells are incubated in the presence of Onalespib for 96 hours at concentrations from 1 nM to 10 μM[2].
Animal Admin	HCT116 cells are injected SC into the right hind flank of male nude BALB/c mice. Tumours are apparent 7 to 10 days later. Mice are arranged into matched groups of 12 according to tumour volume giving a group mean of approximately 100 mm[3] at initiation of dosing. Tumour volumes are measured every 2 days. Statistical significance between groups is assessed using nonparametric one-way ANOVA. Mice are given the lactate salt of Onalespib using a repeated cycle of dosing of once per day for three days, no dose for three days, once per day for three days etc., for four dosing cycles at 60 mg/kg/dose (as free base equivalents) dissolved in 17.5% hydroxypropyl-β-cyclodextrin via the IP route. Control mice receive dose vehicle only via the same route. Tolerability is assessed by recording body weight, clinical observations and survival[1].
References	[1]. Woodhead AJ, et al. 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. J Med Chem. 2010 Aug 26;53(16):5956-69. [2]. Kang MH, et al. Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Jul 15;59(1):185-8.

Density	1.2±0.1 g/cm3
Boiling Point	605.7±55.0 °C at 760 mmHg
Molecular Formula	C₂₄H₃₁N₃O₃
Molecular Weight	409.521
Flash Point	320.1±31.5 °C
Exact Mass	409.236542
PSA	67.25000
LogP	1.52
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.633
Storage condition	-20℃

Hazard Codes	Xi
HS Code	2933990090

2-(2,4-bis-benz...

CAS#:1019890-18-6

~92%

AT13387

CAS#:912999-49-6

Literature: ASTEX THERAPEUTICS LIMITED Patent: WO2008/44041 A1, 2008 ; Location in patent: Page/Page column 295-296 ;

N/A

CAS#:1019890-25-5

~92%

AT13387

CAS#:912999-49-6

Literature: ASTEX THERAPEUTICS LIMITED Patent: US2010/152184 A1, 2010 ; Location in patent: Page/Page column 119; 120 ;

(2,4-Bis-benzyl...

CAS#:913000-35-8

AT13387

CAS#:912999-49-6

Literature: WO2008/44045 A1, ; Page/Page column 319 ; WO 2008/044045 A1

2-(2,4-bis-benz...

CAS#:1019890-18-6

AT13387

CAS#:912999-49-6

N/A

CAS#:1019890-25-5

Literature: WO2008/44034 A1, ; Page/Page column 97-98 ;

5-Bromoisoindoline

CAS#:127168-84-7

AT13387

CAS#:912999-49-6