Product Information
| Molecular Weight: |
433.50 |
| Formula: |
C24H27N5O3 |
| Purity: |
≥ 98% |
| CAS#: |
1316214-52-4 |
| Storage: |
Powder: 4oC 1 year
DMSO: 4oC 3 month
-20oC 1 year |
| Chemical Name: |
2-(diphenylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide |
| Solubility: |
DMSO up to 100 mM |
Biological Activity:
ACY-1215 (Rocilinostat) is a highly potent, selective, and orally
bioavailable inhibitor of histone deacetylase 6 (HDAC6). It inhibits
HDAC6 with an enzymatic IC50 ~ 5nM, and has about 10 fold selectivity against HDAC1, HDAC2, and HDAC3 (58 nM, 48 nM, 51 nM). It has minimal activity (IC50 >1 µM) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2, and has slight activity against HDAC8 (IC50 ~0.1
µM). ACY-1215 selectively targets and binds to HDAC6, thereby
disrupting the Hsp90 protein chaperone system through hyperacetylation
of Hsp90 and preventing the subsequent aggresome protein degradation.
This leads to an accumulation of unfolded and misfolded ubiquitinated
proteins and may eventually induce cancer cell apoptosis, and inhibition
of cancer cell growth. Low doses of ACY-1215 combined with bortezomib
triggered synergistic anti- multiple myeloma (anti-MM) activity,
resulting in protracted endoplasmic reticulum stress and apoptosis via
activation of caspase-3, caspase-8, and caspase-9 and poly (ADP)
ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in
combination with bortezomib was confirmed using 2 different xenograft
SCID mouse models. Currently ACY-1215 is in phase I clinical trials in
combination with Lenalidomide and Dexamethasone for patients with
multiple myeloma.
How to Use:
In vitro: ACY-1215 was used at 1 µM final concentration in vitro and in cellular assays.
In vivo: ACY-1215 was intraperitoneally dosed to
mice consecutively for 5 days a week at 50 mg/kg dissolved in 5%
dextrose in water with 10% DMSO or in combination with bortezomib
(biweekly IV) 0.5 mg/kg dissolved in 0.9% saline solution.
Reference:
- 1. Santo L, et al. Preclinical activity, pharmacodynamic, and
pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in
combination with bortezomib in multiple myeloma. (2012) Blood.
119(11):2579-89.
- 2. http://ash.confex.com/ash/2012/webprogram/Paper52013.html
Products are for research use only. Not for human use.
