Avadomide

Last updated
Avadomide
Avadomide.svg
Legal status
Legal status
  • Investigational
Identifiers
  • 3-(5-Amino-2-methyl-4-oxoquinazolin-3-yl)piperidine-2,6-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C14H14N4O3
Molar mass 286.291 g·mol−1
3D model (JSmol)
  • CC1=NC2=CC=CC(=C2C(=O)N1C3CCC(=O)NC3=O)N
  • InChI=1S/C14H14N4O3/c1-7-16-9-4-2-3-8(15)12(9)14(21)18(7)10-5-6-11(19)17-13(10)20/h2-4,10H,5-6,15H2,1H3,(H,17,19,20)
  • Key:RSNPAKAFCAAMBH-UHFFFAOYSA-N

Avadomide is an experimental cereblon E3 ligase modulator, or thalidomide analog studied to see if it is effective against cancer. [1] [2] [3] [4] [5] [6]

Related Research Articles

<span class="mw-page-title-main">Rituximab</span> Biopharmaceutical drug

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion. Biosimilars of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza, Rixathon, Ruxience, and Truxima.

<span class="mw-page-title-main">Ibritumomab tiuxetan</span> Radioimmunotherapy treatment

Ibritumomab tiuxetan, sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for non-Hodgkin's lymphoma. The drug uses the monoclonal mouse IgG1 antibody ibritumomab in conjunction with the chelator tiuxetan, to which a radioactive isotope is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a methyl group.

<span class="mw-page-title-main">Follicular lymphoma</span> Medical condition

Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells normally occupy the follicles (nodular swirls of various types of lymphocytes) in the germinal centers of lymphoid tissues such as lymph nodes. The cancerous cells in FL typically form follicular or follicle-like structures (see adjacent Figure) in the tissues they invade. These structures are usually the dominant histological feature of this cancer.

<span class="mw-page-title-main">Diffuse large B-cell lymphoma</span> Type of blood cancer

Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, weight loss, and night sweats.

Lumiliximab is an IgG1k monoclonal antibody that targets CD23. It acts as an immunomodulator and was awarded orphan drug status and fast track designation by the FDA.

<span class="mw-page-title-main">Pixantrone</span> Chemical compound

Pixantrone is an experimental antineoplastic (anti-cancer) drug, an analogue of mitoxantrone with fewer toxic effects on cardiac tissue. It acts as a topoisomerase II poison and intercalating agent. The code name BBR 2778 refers to pixantrone dimaleate, the actual substance commonly used in clinical trials.

<span class="mw-page-title-main">Mantle cell lymphoma</span> Type of blood cancer

Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma, comprising about 6% of cases. It is named for the mantle zone of the lymph nodes where it develops. The term 'mantle cell lymphoma' was first adopted by Raffeld and Jaffe in 1991.

<span class="mw-page-title-main">Bendamustine</span> Chemical compound

Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin's lymphoma. It is given by injection into a vein.

Obinutuzumab, sold under the brand name Gazyva among others, is a humanized anti-CD20 monoclonal antibody used as a treatment for cancer. It was originated by GlycArt Biotechnology AG and developed by Roche.

<span class="mw-page-title-main">Nodular lymphocyte predominant Hodgkin lymphoma</span> Medical condition

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a slow-growing CD20 positive form of Hodgkin lymphoma, a cancer of the immune system's B cells.

<span class="mw-page-title-main">Phosphoinositide 3-kinase inhibitor</span>

Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.

Urelumab is a fully human, non‐ligand binding, CD137 agonist immunoglobulin‐γ 4 (IgG4) monoclonal antibody. It was developed utilizing Medarex's UltiMAb(R) technology by Bristol-Myers Squibb for the treatment of cancer and solid tumors. Urelumab promotes anti-tumor immunity, or an immune response against tumor cells, via CD137 activation. The application of Urelumab has been limited due to the fact that it can cause severe liver toxicity.

<span class="mw-page-title-main">Ibrutinib</span> Medication used in cancer treatment

Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. Ibrutinib is therefore used to treat such cancers, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia. Ibrutinib also binds to C-terminal Src Kinases. These are off-target receptors for the BTK inhibitor. Ibrutinib binds to these receptors and inhibits the kinase from promoting cell differentiation and growth. This leads to many different side effects like left atrial enlargement and atrial fibrillation during the treatment of Chronic Lymphocytic Leukemia.

Pidilizumab is a monoclonal antibody being developed by Medivation for the treatment of cancer and infectious diseases. Pidilizumab was originally thought to bind to the PD-1 immune checkpoint molecule, however, recent evidence suggests that Delta-like 1 (DLL1) is its primary binding target while binding to PD-1 is secondary and restricted to non-glycosylated and hypoglycosylated forms of this molecule. Pidilizumab causes in the attenuation of apoptotic processes in lymphocytes, primarily effector/memory T cells.

<span class="mw-page-title-main">Idelalisib</span> Chemical compound

Idelalisib, sold under the brand name Zydelig, is a medication used to treat certain blood cancers.

<span class="mw-page-title-main">Copanlisib</span> Chemical compound

Copanlisib, sold under the brand name Aliqopa, is a medication used for the treatment of adults experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies.

Polatuzumab vedotin, sold under the brand name Polivy, is a CD79b-directed antibody-drug conjugate medication used for the treatment of diffuse large B-cell lymphoma (cancer). It was developed by the Genentech subsidiary of Roche.

<span class="mw-page-title-main">Indolent lymphoma</span> Medical condition

Indolent lymphoma, also known as low-grade lymphoma, is a group of slow-growing non-Hodgkin lymphomas (NHLs). Because they spread slowly, they tend to have fewer signs and symptoms when first diagnosed and may not require immediate treatment. Symptoms can include swollen but painless lymph nodes, unexplained fever, and unintended weight loss.

Iberdomide is an experimental thalidomide analog that works as an cereblon E3 ligase modulator; it has a higher binding affinity than lenalidomide or pomalidomide. It is developed by Bristol Myers Squibb for various cancers and was also tested in people with lupus.

Mezigdomide is a cereblon E3 ligase modulator developed by Bristol Myers Squibb to treat multiple myeloma.

References

  1. Nishi, Hidemi; Gotoh, Kunihito; Tomimaru, Yoshito; Kobayashi, Shogo; Sasaki, Kazuki; Iwagami, Yoshifumi; Yamada, Daisaku; Akita, Hirofumi; Asaoka, Tadafumi; Noda, Takehiro; Takahashi, Hidenori; Tanemura, Masahiro; Doki, Yuichiro; Eguchi, Hidetoshi (October 2023). "Anti-tumor effect of avadomide in gemcitabine-resistant pancreatic ductal adenocarcinoma". Cancer Chemotherapy and Pharmacology. 92 (4): 303–314. doi:10.1007/s00280-023-04531-w. PMC   10435408 . PMID   37491611.
  2. Nastoupil, Loretta J.; Kuruvilla, John; Chavez, Julio C.; Bijou, Fontanet; Witzig, Thomas E.; Santoro, Armando; Flinn, Ian W.; Boccomini, Carola; Kenkre, Vaishalee P.; Corradini, Paolo; Isufi, Iris; Andorsky, David J.; Klein, Leonard M.; Greenwald, Daniel R.; Sangha, Randeep; Shen, Frank; Hagner, Patrick; Li, Yan; Dobmeyer, Juergen; Gong, Nian; Uttamsingh, Shailaja; Pourdehnad, Michael; Ribrag, Vincent (May 2022). "Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma". EJHaem. 3 (2): 394–405. doi:10.1002/jha2.394. PMC   9175947 . PMID   35846031.
  3. Heim, Christopher; Hartmann, Marcus D. (1 March 2022). "High-resolution structures of the bound effectors avadomide (CC-122) and iberdomide (CC-220) highlight advantages and limitations of the MsCI4 soaking system". Acta Crystallographica Section D Structural Biology. 78 (3): 290–298. Bibcode:2022AcCrD..78..290H. doi:10.1107/S2059798322000092. PMC   8900816 . PMID   35234143.
  4. Hagner, Patrick R.; Chiu, Hsiling; Chopra, Vivek S.; Colombo, Martino; Patel, Nisha; Estevez, Maria Ortiz; Waldman, Michelle F.; Loos, Remco; Towfic, Fadi; Gandhi, Anita K. (2 August 2022). "Interactome of Aiolos/Ikaros Reveals Combination Rationale of Cereblon Modulators with HDAC Inhibitors in DLBCL". Clinical Cancer Research. 28 (15): 3367–3377. doi:10.1158/1078-0432.CCR-21-3347. PMC   9662945 . PMID   35583604.
  5. Santiesteban, Daniela Y; Duncan, Aundrietta D; Mirza, Nadeem Q; Jacques, Vincent; DeWitt, Sheila; Iyer, Swami P. (15 November 2022). "SP-3164, a Novel Cereblon-Binding Protein Degrader, Shows Activity in Preclinical Lymphoma Models". Blood. 140 (Supplement 1): 8865–8866. doi:10.1182/blood-2022-167495. S2CID   254268049.
  6. Ribrag, Vincent; Chavez, Julio C.; Boccomini, Carola; Kaplan, Jason; Chandler, Jason C.; Santoro, Armando; Corradini, Paolo; Flinn, Ian W.; Advani, Ranjana; Cassier, Philippe A.; Sangha, Randeep; Kenkre, Vaishalee P.; Isufi, Iris; Uttamsingh, Shailaja; Hagner, Patrick R.; Gandhi, Anita K.; Shen, Frank; Michelliza, Sophie; Haeske, Harald; Hege, Kristen; Pourdehnad, Michael; Kuruvilla, John (February 2022). "Phase Ib study of combinations of avadomide (CC‐122), CC‐223, CC‐292, and rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma". EJHaem. 3 (1): 139–153. doi:10.1002/jha2.375. PMC   9176062 . PMID   35846221.