| Identification | Back Directory | [Name]
(2,4-dihydroxy-5-isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)isoindolin-2-yl)Methanone | [CAS]
912999-49-6 | [Synonyms]
CS-1866
AT-13387
Onalespib
ATI13387X
ATI-13387
AT13387, >=98%
Onalespib Lactate
AT13387(Onalespib)
ONALESPIB;ATI-13387
Onalespib (AT13387)
(2,4-dihydroxy-5-isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)isoindolin-2-yl)Methanone
(2,4-dihydroxy-5-isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)isoindolin-2-yl)Methanone USP/EP/BP
(2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone
4-({5-[(4-Methylpiperazin-1-yl)Methyl]-2,3-dihydro-1H-isoindol-2-yl}carbonyl)-6-(propan-2-yl)benzene-1,3-diol
[1,3-Dihydro-5-[(4-methyl-1-piperazinyl)methyl]-2H-isoindol-2-yl][2,4-dihydroxy-5-(1-methylethyl)phenyl]methanone
Methanone, [1,3-dihydro-5-[(4-methyl-1-piperazinyl)methyl]-2H-isoindol-2-yl][2,4-dihydroxy-5-(1-methylethyl)phenyl]-
[1,3-Dihydro-5-[(4-methyl-1-piperazinyl)methyl]-2H-isoindol-2-yl][2,4-dihydroxy-5-(1-methylethyl)phenyl]methanone AT13387 | [Molecular Formula]
C24H31N3O3 | [MDL Number]
MFCD18633198 | [MOL File]
912999-49-6.mol | [Molecular Weight]
409.52 |
| Chemical Properties | Back Directory | [Boiling point ]
605.7±55.0 °C(Predicted) | [density ]
1.237 | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in H2O; ≥13.25 mg/mL in DMSO; ≥47.7 mg/mL in EtOH with ultrasonic | [form ]
solid | [pka]
8.50±0.48(Predicted) | [color ]
White to off-white | [InChI]
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 | [InChIKey]
IFRGXKKQHBVPCQ-UHFFFAOYSA-N | [SMILES]
C(N1CC2=C(C1)C=CC(CN1CCN(C)CC1)=C2)(C1=CC(C(C)C)=C(O)C=C1O)=O |
| Hazard Information | Back Directory | [Description]
Onalespib, also known as AT13387 or 912999-49-6, is a selective inhibitor of Hsp90 (IC50 = 18 nM). It induces the degradation of specific Hsp90 client proteins, including mutant EGFR, for up to seven days in tumor cell lines in vitro and up to three days in vivo. Onalespib is retained in tumor xenografts and is efficacious in a range of xenograft models. It differs from other HSP90 inhibitors in its longer duration of target inhibition and its favorable toxicity profile in phase I studies in patients with refractory solid tumors. | [Definition]
ChEBI: Onalespib is a member of the class of isoindoles that is isoindole in which the amino group has been acylated by a 2,4-dihydroxy-5-isopropylbenzoyl group and in which position 5 of the isoidole moiety has been substituted by a (4-methylpiperazin-1-yl)methyl group. A second-generation Hsp90 inhibitor. It has a role as a Hsp90 inhibitor and an antineoplastic agent. It is a member of resorcinols, a member of benzamides, a tertiary carboxamide, a member of isoindoles and a N-alkylpiperazine. | [Synthesis]
The product of step 11 (0.9 kg, 1.53 mol) was dissolved in a solvent mixture of isopropanol (6.8 L) and water (1.04 L). 10% Pd/C catalyst (90 g) and potassium carbonate (0.212 kg, 1.53 mol) were added to the solution under nitrogen protection. Subsequently, the suspension was hydrogenated for 60 to 70 min under hydrogen pressure of 3 bar. After completion of the reaction, the reaction mixture was diluted with water (0.5 L) and filtered. A 30% aqueous hydrochloric acid solution (0.85 kg, diluted with 5.42 kg of water) was added to the filtrate and then concentrated under vacuum at 60 °C to remove 10 L of isopropanol. Water (0.45 L) was added to the concentrated solution and concentration was continued until another 10 L of isopropanol was removed. The organic phase was extracted with water (4.61 L) and then diluted with acetonitrile (4.06 L). The pH was adjusted to 7.5-8.5 by dropwise addition of concentrated aqueous ammonia solution (0.35 kg). the resulting suspension was stirred for 2.5 h, followed by filtration to remove the solids. The residue was washed with acetonitrile (2 x 0.8 L) and dried to constant weight at 40 °C to give a final product of (2,4-dihydroxy-5-isopropylphenyl)(5-((4-methylpiperazin-1-yl)methyl)isoindolin-2-yl)methanone 588 g in 94% yield. | [target]
Hsp90 | [storage]
Store at -20°C | [Mode of action]
Onalespib selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability and degradation of many oncogenic signaling proteins and has been used as a biomarker of HSP90 inhibition. | [References]
Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas
https://pubchem.ncbi.nlm.nih.gov/compound/Onalespib |
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