Difference between revisions of "Ricolinostat (ACY-1215)"

Latest revision as of 12:45, 27 July 2023

General information

Class/mechanism from the NCI Drug Dictionary: An orally bioavailable, specific inhibitor of histone deacetylase 6 (HDAC6) with potential antineoplastic activity. Ricolinostat selectively targets and binds to HDAC6, thereby disrupting the Hsp90 protein chaperone system through hyperacetylation of Hsp90 and preventing the subsequent aggresomal 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.^[1]^[2]^[3]
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Preliminary data

Multiple myeloma

Vogl DT, Raje N, Jagannath S, Richardson P, Hari P, Orlowski R, Supko JG, Tamang D, Yang M, Jones SS, Wheeler C, Markelewicz RJ, Lonial S. Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma. Clin Cancer Res. 2017 Jul 1;23(13):3307-3315. Epub 2017 Jan 4. link to original article link to PMC article PubMed

Also known as

Code name: ACY-1215
Generic name: rocilinostat

References

↑ Ricolinostat in Multiple Myeloma, Acetylon Pharmaceuticals
↑ Andrew J Yee, MD, Peter M. Voorhees, MD, William Bensinger, Jesus G. Berdeja, MD, Jeffrey G Supko, PhD, Paul G. Richardson, David Tamang, PhD, Simon S Jones, PhD, Gretchen Patrick, Catherine Wheeler, MD and Noopur Raje, MD. Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma. 2014 ASH Annual Meeting abstract 4772. link to abstract
↑ Noopur Raje, MD, Parameswaran N Hari, MD, MRCP, MS, Dan T. Vogl, MD, MSCE, Sundar Jagannath, MD, Robert Z. Orlowski, M.D., Ph.D., Jeffrey G Supko, PhD, Patricia Stephenson, ScD, Simon S Jones8, Catherine Wheeler, MD and Sagar Lonial, MD. Rocilinostat (ACY-1215), a Selective HDAC6 Inhibitor, Alone and in Combination with Bortezomib in Multiple Myeloma: Preliminary Results From the First-in-Humans Phase I/II Study. 2012 ASH Annual Meeting abstract 4061. link to abstract

[1] Ricolinostat in Multiple Myeloma, Acetylon Pharmaceuticals

[2] Andrew J Yee, MD, Peter M. Voorhees, MD, William Bensinger, Jesus G. Berdeja, MD, Jeffrey G Supko, PhD, Paul G. Richardson, David Tamang, PhD, Simon S Jones, PhD, Gretchen Patrick, Catherine Wheeler, MD and Noopur Raje, MD. Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma. 2014 ASH Annual Meeting abstract 4772. link to abstract

[3] Noopur Raje, MD, Parameswaran N Hari, MD, MRCP, MS, Dan T. Vogl, MD, MSCE, Sundar Jagannath, MD, Robert Z. Orlowski, M.D., Ph.D., Jeffrey G Supko, PhD, Patricia Stephenson, ScD, Simon S Jones8, Catherine Wheeler, MD and Sagar Lonial, MD. Rocilinostat (ACY-1215), a Selective HDAC6 Inhibitor, Alone and in Combination with Bortezomib in Multiple Myeloma: Preliminary Results From the First-in-Humans Phase I/II Study. 2012 ASH Annual Meeting abstract 4061. link to abstract

[1]

[2]

[3]

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+{{TOC limit|limit=4}}
 ==General information==
-Class/mechanism: Selective HDAC6 inhibitor.  Histone deacetylase (HDAC) inhibitors result in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes.  This modulation may result in decreased expression of oncogenes, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.  It is hypothesized that selectively inhibiting HDAC6 rather than additional members of the HDAC family may be able to maintain efficacy while resulting in fewer side effects associated with pan-HDAC inhibitors, such as myelosuppression, fatigue, nausea, vomiting, and diarrhea.<ref>[http://www.acetylon.com/ricolinostat_in_multiple_myeloma.php Ricolinostat in Multiple Myeloma, Acetylon Pharmaceuticals]</ref><ref name=YeeASH2014>Andrew J Yee, MD, Peter M. Voorhees, MD, William Bensinger, Jesus G. Berdeja, MD, Jeffrey G Supko, PhD, Paul G. Richardson, David Tamang, PhD, Simon S Jones, PhD, Gretchen Patrick, Catherine Wheeler, MD and Noopur Raje, MD. Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma. 2014 ASH Annual Meeting abstract 4772. [https://ash.confex.com/ash/2014/webprogram/Paper75422.html link to abstract]</ref><ref name=RajeASH2012>Noopur Raje, MD, Parameswaran N Hari, MD, MRCP, MS, Dan T. Vogl, MD, MSCE, Sundar Jagannath, MD, Robert Z. Orlowski, M.D., Ph.D., Jeffrey G Supko, PhD, Patricia Stephenson, ScD, Simon S Jones8, Catherine Wheeler, MD and Sagar Lonial, MD. Rocilinostat (ACY-1215), a Selective HDAC6 Inhibitor, Alone and in Combination with Bortezomib in Multiple Myeloma:  Preliminary Results From the First-in-Humans Phase I/II Study. 2012 ASH Annual Meeting abstract 4061. [https://ash.confex.com/ash/2012/webprogram/Paper52013.html link to abstract]</ref>
+Class/mechanism from the [https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=698408 NCI Drug Dictionary]: An orally bioavailable, specific inhibitor of histone deacetylase 6 (HDAC6) with potential antineoplastic activity. Ricolinostat selectively targets and binds to HDAC6, thereby disrupting the Hsp90 protein chaperone system through hyperacetylation of Hsp90 and preventing the subsequent aggresomal 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.<ref>[http://www.acetylon.com/ricolinostat_in_multiple_myeloma.php Ricolinostat in Multiple Myeloma, Acetylon Pharmaceuticals]</ref><ref>Andrew J Yee, MD, Peter M. Voorhees, MD, William Bensinger, Jesus G. Berdeja, MD, Jeffrey G Supko, PhD, Paul G. Richardson, David Tamang, PhD, Simon S Jones, PhD, Gretchen Patrick, Catherine Wheeler, MD and Noopur Raje, MD. Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma. 2014 ASH Annual Meeting abstract 4772. [https://ash.confex.com/ash/2014/webprogram/Paper75422.html link to abstract]</ref><ref>Noopur Raje, MD, Parameswaran N Hari, MD, MRCP, MS, Dan T. Vogl, MD, MSCE, Sundar Jagannath, MD, Robert Z. Orlowski, M.D., Ph.D., Jeffrey G Supko, PhD, Patricia Stephenson, ScD, Simon S Jones8, Catherine Wheeler, MD and Sagar Lonial, MD. Rocilinostat (ACY-1215), a Selective HDAC6 Inhibitor, Alone and in Combination with Bortezomib in Multiple Myeloma:  Preliminary Results From the First-in-Humans Phase I/II Study. 2012 ASH Annual Meeting abstract 4061. [https://ash.confex.com/ash/2012/webprogram/Paper52013.html link to abstract]</ref>
 <br>Route: PO
 <br>Extravasation: n/a
-For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer.  Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.
+For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.
-==Diseases for which it is used==
+==Preliminary data==
-*[[Multiple myeloma]]
-==Preliminary data==
 ===[[Multiple myeloma]]===
-====Lenalidomide, Dexamethasone, Ricolinostat====
+# Vogl DT, Raje N, Jagannath S, Richardson P, Hari P, Orlowski R, Supko JG, Tamang D, Yang M, Jones SS, Wheeler C, Markelewicz RJ, Lonial S. Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma. Clin Cancer Res. 2017 Jul 1;23(13):3307-3315. Epub 2017 Jan 4. [https://doi.org/10.1158/1078-0432.ccr-16-2526 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5496796/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28053023/ PubMed]
-=====Regimen, Yee et al. 2014=====
-''Doses & schedule of Ricolinostat varied at different points in the study. The regimen below is based on "Part B" as described in Yee et al. 2014''
-*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
-*[[Dexamethasone (Decadron)]] 40 mg PO once per week
-*[[Ricolinostat (ACY-1215, Rocilinostat)]] 160 mg PO BID once per day on days 1 to 21
-'''28-day cycles'''
-=====References=====
-# Andrew J Yee, MD, Peter M. Voorhees, MD, William Bensinger, Jesus G. Berdeja, MD, Jeffrey G Supko, PhD, Paul G. Richardson, David Tamang, PhD, Simon S Jones, PhD, Gretchen Patrick, Catherine Wheeler, MD and Noopur Raje, MD. Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma. 2014 ASH Annual Meeting abstract 4772. [https://ash.confex.com/ash/2014/webprogram/Paper75422.html link to abstract]
-====Bortezomib, Dexamethasone, Rocilinostat====
-=====Regimen, Raje et al. 2012=====
-''Different doses & schedule of Rocilinostat were used at different points in this Phase I/II Study. Please refer to Raje et al. 2012 regarding the various doses of Rocilinostat used in the monotherapy part.''
-*[[Bortezomib (Velcade)]] 1.0 mg/m2 (route not specified) once per day on days 1, 4, 8, 11
-*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
-*[[Ricolinostat (ACY-1215, Rocilinostat)]] 40 mg PO (40 mg was the "starting dose."  Schedule was not clearly specified; during the monotherapy "Part 1" of the study, it was given on days 1 to 5 and days 8 to 12)
-'''21-day cycles x "up to 6 cycles of therapy, or more if experiencing clinical benefit"'''
-=====References=====
-# Noopur Raje, MD, Parameswaran N Hari, MD, MRCP, MS, Dan T. Vogl, MD, MSCE, Sundar Jagannath, MD, Robert Z. Orlowski, M.D., Ph.D., Jeffrey G Supko, PhD, Patricia Stephenson, ScD, Simon S Jones8, Catherine Wheeler, MD and Sagar Lonial, MD. Rocilinostat (ACY-1215), a Selective HDAC6 Inhibitor, Alone and in Combination with Bortezomib in Multiple Myeloma:  Preliminary Results From the First-in-Humans Phase I/II Study. 2012 ASH Annual Meeting abstract 4061. [https://ash.confex.com/ash/2012/webprogram/Paper52013.html link to abstract]
 ==Also known as==
-ACY-1215, Rocilinostat
+*'''Code name:''' ACY-1215
+*'''Generic name:''' rocilinostat
 ==References==
 <references/>
-[[Category:Drug index]]
+[[Category:Drugs]]
-[[Category:Chemotherapy]]
+[[Category:Oral medications]]
-[[Category:Oral chemotherapy]]
 [[Category:HDAC inhibitors]]
-[[Category:Multiple myeloma medications]]
+[[Category:Multiple myeloma medications (investigational)]]
-[[Category:Investigational]]
+[[Category:Investigational drugs]]