Obatoclax

Obatoclax mesylate, also known as GX15-070, is an experimental drug for the treatment of various types of cancer. It was discovered by Gemin X, which was acquired by Cephalon, which has since been acquired by Teva Pharmaceuticals.[1] Several Phase II clinical trials were completed that investigated use of Obatoclax in the treatment of leukemia, lymphoma, myelofibrosis, and mastocytosis.[2][3][4]

Obatoclax
Names
IUPAC name
2-(2-((3,5-Dimethyl-1H-pyrrol-2-yl)methylene)-3-methoxy-2H-pyrrol-5-yl)-1H-indole
Other names
GX15-070
Identifiers
3D model (JSmol)
ChemSpider
UNII
Properties
C20H19N3O
Molar mass 317.392 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Mechanism of action

Obatoclax is an inhibitor of the Bcl-2 family of proteins.[5] This inhibition induces apoptosis in cancer cells, preventing tumor growth. Solubility has been an issue in the development of the drug.[6]

Clinical trials

Clinical trial results have been published for treatment of acute myeloid leukemia,[7] small cell lung cancer,[8] Hodgkin's lymphoma,[9] myelodysplastic syndromes,[10]

Teva halted a phase III trial in patients with lung cancer before it had begun, citing "business decisions" as the reason.[11]

gollark: I use Arch Linux, which is rolling release (there are no fixed versions of the distro, you just update your packages whenever they get updated), very flexible (you install it manually, choosing partition layout, DE, extra software, etc), and has the AUR, a giant collection of user-packaged software.
gollark: Plus different stuff for managing services.
gollark: Many of them have different sets of available packages and stuff, or different package managers, or different desktop environments (you can usually swap them, though).
gollark: There are quite significant differences between distros, actually.
gollark: But I don't think it's the most common or easy distro.

See also

References
  1. Cephalon Announces Definitive Agreement to Acquire Gemin X, March 21, 2011
  2. Parikh, Sameer A.; Kantarjian, Hagop; Schimmer, Aaron; Walsh, William; Asatiani, Ekatherine; El-Shami, Khaled; Winton, Elliott; Verstovsek, Srdan (2010). "Phase II Study of Obatoclax Mesylate (GX15-070), a Small-Molecule BCL-2 Family Antagonist, for Patients with Myelofibrosis". Clinical Lymphoma, Myeloma & Leukemia. 10 (4): 285–9. doi:10.3816/CLML.2010.n.059. PMID 20709666.
  3. Gemin X Presents New Data on Obatoclax at the American Society of Hematology Meeting, Dec 9, 2008
  4. Obatoclax at ClinicalTrials.gov
  5. Konopleva, M.; Watt, J.; Contractor, R.; Tsao, T.; Harris, D.; Estrov, Z.; Bornmann, W.; Kantarjian, H.; Viallet, J.; Samudio, I.; Andreeff, M. (2008). "Mechanisms of Antileukemic Activity of the Novel Bcl-2 Homology Domain-3 Mimetic GX15-070 (Obatoclax)". Cancer Research. 68 (9): 3413–20. doi:10.1158/0008-5472.CAN-07-1919. PMC 4096127. PMID 18451169.
  6. Nguyen, Mai; Cencic, Regina; Ertel, Franziska; Bernier, Cynthia; Pelletier, Jerry; Roulston, Anne; Silvius, John R.; Shore, Gordon C. (2015). "Obatoclax is a direct and potent antagonist of membrane-restricted Mcl-1 and is synthetic lethal with treatment that induces Bim". BMC Cancer. 15. doi:10.1186/s12885-015-1582-5. PMC 4522062.
  7. Schimmer, Aaron D.; Raza, Azra; Carter, Thomas H.; Claxton, David; Erba, Harry; Deangelo, Daniel J.; Tallman, Martin S.; Goard, Carolyn; Borthakur, Gautam (2014). "A Multicenter Phase I/II Study of Obatoclax Mesylate Administered as a 3- or 24-Hour Infusion in Older Patients with Previously Untreated Acute Myeloid Leukemia". PLoS ONE. 9 (10): e108694. Bibcode:2014PLoSO...9j8694S. doi:10.1371/journal.pone.0108694. PMC 4186779. PMID 25285531.
  8. Langer, Corey J.; Albert, Istvan; Ross, Helen J.; Kovacs, Peter; Blakely, L. Johnetta; Pajkos, Gabor; Somfay, Attila; Zatloukal, Petr; Kazarnowicz, Andrzej; Moezi, Mehdi M.; Schreeder, Marshall T.; Schnyder, Judy; Ao-Baslock, Ada; Pathak, Ashutosh K.; Berger, Mark S. (2014). "Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer". Lung Cancer. 85 (3): 420–8. doi:10.1016/j.lungcan.2014.05.003. PMID 24997137.
  9. Oki, Y.; Copeland, A.; Hagemeister, F.; Fayad, L. E.; Fanale, M.; Romaguera, J.; Younes, A. (2012). "Experience with obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist in patients with relapsed or refractory classical Hodgkin lymphoma". Blood. 119 (9): 2171–2. doi:10.1182/blood-2011-11-391037. PMID 22383790.
  10. Arellano, Martha L.; Borthakur, Gautam; Berger, Mark; Luer, Jill; Raza, Azra (2014). "A Phase II, Multicenter, Open-Label Study of Obatoclax Mesylate in Patients with Previously Untreated Myelodysplastic Syndromes with Anemia or Thrombocytopenia". Clinical Lymphoma, Myeloma & Leukemia. 14 (6): 534–9. doi:10.1016/j.clml.2014.04.007. PMID 25052051.
  11. Clinical trial number NCT01563601 for "Efficacy and Safety of Obatoclax Mesylate in Combination With Carboplatin and Etoposide Compared With Carboplatin and Etoposide Alone in Chemotherapy-Naive Patients With Extensive-Stage Small Cell Lung Cancer" at ClinicalTrials.gov


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