Pomalidomide

Overview

Pomalidomide, sold under the brand name Pomalyst among others, is an anti-cancer medication used for the treatment of multiple myeloma and AIDS-related Kaposi sarcoma. It inhibits angiogenesis, the formation of new blood vessels.[1] WP

Pomalidomide was approved for medical use in the United States in February 2013, and in the European Union in August 2013. It is available as a generic medication.[2][3][4] WP

Uses, dosage and effects

Medical uses

In the European Union, pomalidomide, in combination with bortezomib and dexamethasone, is indicated for the treatment of adults with multiple myeloma who have received at least one prior treatment regimen including lenalidomide; and in combination with dexamethasone for the treatment of adults with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy.[3] WP

In the United States, pomalidomide is indicated, in combination with dexamethasone, for the treatment of people with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy; and for the treatment of people with AIDS-related Kaposi sarcoma after failure of highly active antiretroviral therapy (HAART) or in people with Kaposi sarcoma who are HIV-negative.[5–8] WP

Risks and side effects

Side effects

Pomalidomide can cause harm to unborn babies when administered during pregnancy.[3] WP

Pomalidomide is present in the semen of people receiving the drug.[1][3] WP

Pharmacology

Mechanism of action

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 inhibitors including rolipram and pentoxifylline do not inhibit myeloma cell growth or angiogenesis.[9] WP

Pomalidomide works as a cereblon E3 ligase modulator.[10] WP

History

History

The parent compound of pomalidomide, thalidomide, was originally discovered to inhibit angiogenesis in 1994. Based upon this discovery, thalidomide was taken into clinical trials for cancer, leading to its ultimate FDA approval for multiple myeloma. 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. This dual activity of pomalidomide makes it more efficacious than thalidomide in vitro and in vivo.[9][11][12][13] WP

Clinical trials

Phase I trial results showed tolerable side effects.[14] WP

Phase II clinical trials for multiple myeloma and myelofibrosis reported promising results.[15][16] WP

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 people taking pomalidomide and dexamethasone versus dexamethasone alone.[17] WP

Chemistry

Formula

C13H11N3O4 PC

CAS number

19171-19-8 PC

Molar mass (g/mol)

273.24 PC

IUPAC name (computed by PubChem)

4-amino-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione PC

SMILES

C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)N PC

InChIKey

UVSMNLNDYGZFPF-UHFFFAOYSA-N PC

PubChem CID

134780

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Pomalyst- pomalidomide capsule. 7 December 2017
2. Journal / agency Drug Approval Package: Pomalyst (pomalidomide) Capsules NDA #204026. 8 February 2013
3. Journal / agency Imnovid EPAR
4. Journal / agency 2020 First Generic Drug Approvals. 23 February 2021
5. Other Pomalidomide. 13 February 2013
6. Journal / agency FDA grants accelerated approval to pomalidomide for Kaposi sarcoma. 15 May 2020
7. Other FDA approves pomalidomide for AIDS-related Kaposi sarcoma. 15 May 2020
8. Journal / agency Cancer Accelerated Approvals. 1 May 2023
9. Journal / agency D'Amato RJ, Lentzsch S, Anderson KC, Rogers MS. Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma. Seminars in Oncology. December 2001. doi:10.1016/S0093-7754(01)90031-4 · PMID 11740816
10. Journal / agency Asatsuma-Okumura T, Ito T, Handa H. Molecular mechanisms of cereblon-based drugs. Pharmacology & Therapeutics. October 2019. doi:10.1016/j.pharmthera.2019.06.004 · PMID 31202702
11. Journal / agency D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proceedings of the National Academy of Sciences of the United States of America. April 1994. doi:10.1073/pnas.91.9.4082 · PMID 7513432 · PMC43727
12. Other Altman D. From Thalidomide to Pomalyst: Better Living Through Chemistry
13. Journal / agency Lentzsch S, Rogers MS, LeBlanc R, Birsner AE, Shah JH, Treston AM, Anderson KC, D'Amato RJ. S-3-Amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice. Cancer Research. April 2002. PMID 11956087
14. Journal / agency Streetly MJ, Gyertson K, Daniel Y, Zeldis JB, Kazmi M, Schey SA. Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. British Journal of Haematology. April 2008. doi:10.1111/j.1365-2141.2008.07013.x · PMID 18324965
15. Other Promising Results From 2 Trials Highlighting Pomalidomide Presented At ASH. 11 December 2008
16. Other Tefferi A. Pomalidomide Therapy in Anemic Patients with Myelofibrosis: Results from a Phase-2 Randomized Multicenter Study. 8 December 2008
17. Journal / agency Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. The Lancet. Oncology. September 2013. doi:10.1016/s1470-2045(13)70380-2 · PMID 24007748

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