912999-49-6
912999-49-6 structure
- Name: AT13387
- Chemical Name: (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone
- CAS Number: 912999-49-6
- Molecular Formula: C24H31N3O3
- Molecular Weight: 409.521
- Catalog: Biochemical Inhibitor Cytoskeletal Signaling HSP eg HSP90 inhibitor
- Create Date: 2018-06-03 08:00:00
- Modify Date: 2024-01-09 19:09:42
-
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 |
|---|---|
| Synonyms |
UNII-Q7Y33N57ZZ
(2,4-dihydroxy-5-isopropyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl]-methanone AT-13387 Methanone, [1,3-dihydro-5-[(4-methyl-1-piperazinyl)methyl]-2H-isoindol-2-yl][2,4-dihydroxy-5-(1-methylethyl)phenyl]- AT13387 2-(2,4-dihydroxy-5-isopropylbenzoyl)-5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindole CS-0969 N-(2,4-dihydroxy-5-iso-propylbenzoyl)(5-(4-methylpiperazin-1-yl)methyl)-iso-indoline (2,4-Dihydroxy-5-isopropylphenyl){5-[(4-methyl-1-piperazinyl)methyl]-1,3-dihydro-2H-isoindol-2-yl}methanone Onalespib |
| Description | Onalespib (AT13387) is a potent inhibitor of Hsp90, with a Kd of 0.71 nM. |
|---|---|
| Related Catalog | |
| 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 |
| 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 |
|
~92%
912999-49-6 |
| Literature: ASTEX THERAPEUTICS LIMITED Patent: WO2008/44041 A1, 2008 ; Location in patent: Page/Page column 295-296 ; |
|
~92%
912999-49-6 |
| Literature: ASTEX THERAPEUTICS LIMITED Patent: US2010/152184 A1, 2010 ; Location in patent: Page/Page column 119; 120 ; |
|
~%
912999-49-6 |
| Literature: WO2008/44045 A1, ; Page/Page column 319 ; WO 2008/044045 A1 |
|
~%
912999-49-6 |
| Literature: WO2008/44034 A1, ; Page/Page column 97-98 ; |
|
~%
912999-49-6 |
| Literature: Journal of Organic Chemistry, , vol. 77, # 24 p. 11296 - 11301 |
|
~%
912999-49-6 |
| Literature: Journal of Organic Chemistry, , vol. 77, # 24 p. 11296 - 11301 |
|
~%
912999-49-6 |
| Literature: Journal of Organic Chemistry, , vol. 77, # 24 p. 11296 - 11301 |
|
~%
912999-49-6 |
| Literature: Journal of Organic Chemistry, , vol. 77, # 24 p. 11296 - 11301 |
|
~%
912999-49-6 |
| Literature: Journal of Organic Chemistry, , vol. 77, # 24 p. 11296 - 11301 |
| Precursor 5 | |
|---|---|
| DownStream 0 | |
| HS Code | 2933990090 |
|---|---|
| Summary | 2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |