| Identification | Back Directory | [Name]
ACY-1215 | [CAS]
1316214-52-4 | [Synonyms]
ACY 63
CS-583
ACY-1215
Rocilinostat
Ricolinostat
ACY-1215/ACY1215
Rocilinostat, >=99%
Rocilinostat (ACY-1215)
Ricolinostat (ACY-1215)
ACY-1215 (Rocilinostat)
Parathyroid hormone - Shire
RICOLINOSTAT;ACY1215;ACY 1215
1316214-52-4 ACY1215,ROCILINOSTAT
ROCILINOSTAT; ACY1215; ACY 1215;RICOLINOSTAT
7-{[2-(Diphenylamino)pyrimidin-5-yl]formamido}-N-hydroxyheptanamide
2-(Diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-5-pyrimidinecarboxamide
2-(DiphenylaMino)-N-(7-(hydroxyaMino)-7-oxoheptyl)pyriMidine-5-carboxaMide
5-Pyrimidinecarboxamide, 2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-
N-[7-(hydroxyamino)-7-oxoheptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide
2-(Diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-5-pyrimidinecarboxamide ACY 1215 | [Molecular Formula]
C24H27N5O3 | [MDL Number]
MFCD22666356 | [MOL File]
1316214-52-4.mol | [Molecular Weight]
433.5 |
| Chemical Properties | Back Directory | [Melting point ]
189 - 191°C | [density ]
1.239±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C Freezer | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
9.47±0.20(Predicted) | [color ]
White to Off-White |
| Hazard Information | Back Directory | [Description]
ACY-1215 is an inhibitor of histone deacetylase 6 (HDAC6; IC50 = 5 nM).1 It is at least 10-fold less active against other HDACs in enzymatic assays. ACY-1215 shows synergistic activity with the proteasome inhibitor bortezomib (Item No. 10008822) against multiple myeloma (MM) cells, inducing protracted endoplasmic reticulum stress and apoptosis.1,2 ACY-1215 combined with proteasome inhibitors suppresses tumor growth and increases survival in mice with MM and mantle cell lymphoma xenografts.2,1,3 A multicenter phase I trial examining ACY-1215 combined with the E3 ligase inhibitor lenalidomide (Item No. 14643) and dexamethasone (Item No. 11015) in multiple myeloma found inhibition of HDAC6 in vivo.4 ACY-1215 also diminishes liver cyst development and fibrosis in a rat model of polycystic liver disease.5 | [Uses]
This compound acts as a selective HDAC-6 (histone deacetylase) inihibitor. HDAC is linked to the transcription of DNA in cancers, including multiple myeloma (MM). | [Definition]
ChEBI: N-[7-(hydroxyamino)-7-oxoheptyl]-2-(N-phenylanilino)-5-pyrimidinecarboxamide is a pyrimidinecarboxylic acid. | [Synthesis]
Compound 6 (CAS:1316216-07-5) (2.0 g, 4.6 mmol) was taken as raw material and stirred with sodium hydroxide (2N, 20 mL) in a solvent mixture of methanol (50 mL) and dichloromethane (25 mL) for 10 minutes at 0°C. Subsequently, hydroxylamine (50%, 10 mL) pre-cooled to 0°C was added to the above mixture. The reaction mixture was continued to be stirred at room temperature for 20 minutes. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure and the resulting mixture was neutralized with 1 M hydrochloric acid to produce a white precipitate. The crude product was filtered and purified by preparative high performance liquid chromatography (pre-HPLC) to give the final target product 2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]pyrimidine-5-carboxamide as a white solid (950 mg, 48% yield). | [in vivo]
Mice treated with Ricolinostat (ACY-1215), PS-341, or Ricolinostat plus PS-341 show a significant delay in tumor growth (P=0.01, P=0.006, and P<0.0001, respectively). Combined treatment with Ricolinostat and PS-341 shows significant suppression of tumor growth and significantly prolonged overall survival (OS) compare with the control group (17 days in the control vs 40 days in the combination-treated group, P<0.0001) and the Ricolinostat (ACY-1215)-treated group (22 days in the PS-341 group vs 40 days in the combination-treated group, P<0.0001). Weight loss in the combination-treated group is between 4% and 12% compare with the same-day control group values during treatment, with complete recovery after the last injection. As is observed in the plasmacytoma model, a significant therapeutic advantage is found by combining Ricolinostat with PS-341 compare with either agent alone[1]. | [target]
HDAC6 | [IC 50]
HDAC6: 4.7 nM (IC50); HDAC2: 48 nM (IC50); HDAC3: 51 nM (IC50); HDAC1: 58 nM (IC50); HDAC8: 100 nM (IC50); HDAC7: 1400 nM (IC50); HDAC5: 5000 nM (IC50); HDAC4: 7000 nM (IC50) | [References]
[1] Patent: WO2011/91213, 2011, A2. Location in patent: Page/Page column 73; 75-76
[2] Patent: WO2013/13113, 2013, A2. Location in patent: Page/Page column 70
[3] Patent: US2015/99744, 2015, A1. Location in patent: Paragraph 0237
[4] Patent: US2015/105384, 2015, A1. Location in patent: Paragraph 0406
[5] Patent: US2015/105358, 2015, A1. Location in patent: Paragraph 0396-0397 |
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