Pomalidomide

From Infogalactic: the planetary knowledge core
Jump to: navigation, search
Pomalidomide
200px
200px
Systematic (IUPAC) name
(RS)-4-Amino-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
Clinical data
Trade names Imnovid, Pomalyst
Licence data EMA:Link, US FDA:link
Pregnancy
category
  • US: X (Contraindicated)
Legal status
Routes of
administration		 Oral
Pharmacokinetic data
Protein binding 12–44%
Metabolism Hepatic (mostly CYP1A2 and CYP3A4 mediated; some minor contributions by CYP2C19 and CYP2D6)
Biological half-life 7.5 hours
Excretion Urine (73%), faeces (15%)
Identifiers
CAS Number 19171-19-8 YesY
ATC code L04AX06 (WHO)
PubChem CID: 134780
IUPHAR/BPS 7348
ChemSpider 118785 N
UNII D2UX06XLB5 N
ChEMBL CHEMBL43452 N
Chemical data
Formula C13H11N3O4
Molecular mass 273.24 g/mol
  • C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)N
  • InChI=1S/C13H11N3O4/c14-7-3-1-2-6-10(7)13(20)16(12(6)19)8-4-5-9(17)15-11(8)18/h1-3,8H,4-5,14H2,(H,15,17,18) N
  • Key:UVSMNLNDYGZFPF-UHFFFAOYSA-N N
 NYesY (what is this?)  (verify)

Pomalidomide (INN, originally CC-4047 or 3-amino-thalidomide, trade name Pomalyst[1] in the US and Imnovid in Europe) is a derivative of thalidomide marketed by Celgene. It is anti-angiogenic and also acts as an immunomodulator. Pomalidomide was approved in February 2013 by the U.S. Food and Drug Administration (FDA) as a treatment for relapsed and refractory multiple myeloma.[2] It received a similar approval from the European Commission in August 2013.[3]

Origin and development

The parent compound of pomalidomide, thalidomide, was originally discovered to inhibit angiogenesis in 1994.[4] Based upon this discovery, thalidomide was taken into clinical trials for cancer, leading to its ultimate FDA approval for multiple myeloma.[5] Structure-activity studies revealed that amino substituted thalidomide had improved antitumor activity, which was due to its ability to directly inhibit both the tumor cell and vascular compartments of myeloma cancers.[6] This dual activity of pomalidomide makes it more efficacious than thalidomide in vitro and in vivo.[7]

Clinical trials

Phase I trial results showed tolerable side effects.[8]

Phase II clinical trials for multiple myeloma and myelofibrosis reported 'promising results'.[9][10]

Phase III results showed significant extension of progression-free survival, and overall survival (median 11.9 months vs. 7.8 months; p = 0.0002) in patients taking pomalidomide and dexamethasone vs. dexamethasone alone.[11]

Mechanism

Pomalidomide directly inhibits angiogenesis and myeloma cell growth. This dual effect is central to its activity in myeloma, rather than other pathways such as TNF alpha inhibition, since potent TNF alpha inhibitors including rolipram and pentoxifylline do not inhibit myeloma cell growth or angiogenesis.[6] Up regulation of Interferon gamma, IL-2 and IL-10 as well as down regulation of IL-6 have been reported for pomalidomide. These changes may contribute to pomalidomide's anti-angiogenic and anti-myeloma activities.

Pregnancy and sexual contact warnings

Because pomalidomide can cause harm to unborn babies when administered during pregnancy, women taking pomalidomide must not become pregnant. Women must produce two negative pregnancy tests and use contraception methods before beginning pomalidomide. Women must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of pomalidomide therapy. Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for up to 28 days after discontinuing pomalidomide, even if they have undergone a successful vasectomy. Male patients taking pomalidomide must not donate sperm.[12]

See also

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ http://vectorblog.org/2013/04/from-thalidomide-to-pomalyst-better-living-through-chemistry/
  6. ↑ 6.0 6.1 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

Retrieved from "https://infogalactic.com/w/index.php?title=Pomalidomide&oldid=722455259"