{"id":6846,"date":"2024-12-06T13:00:13","date_gmt":"2024-12-06T12:00:13","guid":{"rendered":"https:\/\/beigen.vipdev.lndo.site\/us\/?post_type=compound&p=6846"},"modified":"2025-04-28T22:23:00","modified_gmt":"2025-04-28T20:23:00","slug":"sonrotoclax","status":"publish","type":"compound","link":"https:\/\/beonemedaffairs.com\/us\/compound\/6846\/sonrotoclax\/","title":{"rendered":"Sonrotoclax"},"content":{"rendered":"","protected":false},"template":"","meta":{"_acf_changed":false,"editor_notices":[]},"post-tag":[537],"class_list":["post-6846","compound","type-compound","status-publish","hentry","post-tag-sonrotoclax","disease_state-acute-myeloid-leukemia","disease_state-b-cell-malignancies","disease_state-chronic-lymphocytic-leukemia","disease_state-hematologic-malignancies","disease_state-mantle-cell-lymphoma","disease_state-multiple-myeloma","disease_state-small-lymphocytic-lymphoma","disease_state-waldenstroms-macroglobulinemia","molecule-sonrotoclax"],"acf":{"header_text":"Sonrotoclax is a potent and selective inhibitor of BCL2.","summary":"Sonrotoclax is an investigational potent and selective inhibitor of BCL2.","tags":[537],"text":"","approval_status_for_filter":"investigational","accordion_presentation":"expanded","overview":"Sonrotoclax is a potent and selective investigational inhibitor of B-cell lymphoma 2 (BCL2) with a differentiated profile. In preclinical tumor models, sonrotoclax demonstrated more potent antitumor activity compared to venetoclax.1<\/sup>\r\n\r\nIn ongoing Phase 1 studies, it was generally well tolerated and demonstrated preliminary antitumor activity in patients with B-cell malignancies, acute myeloid leukemia (AML), and multiple myeloma (MM).2-8<\/sup> Sonrotoclax has been granted Fast Track Designation by the FDA for relapsed\/refractory mantle cell lymphoma (MCL) and relapsed\/refractory Waldenstr\u00f6m\u2019s macroglobulinemia (WM).\r\n\r\nReferences<\/strong>\r\n
    \r\n \t
  1. Hu, N.\u00a0et al.<\/em>Abstract 3077: Preclinical characterization of BGB-11417, a potent and selective Bcl-2 inhibitor with superior antitumor activities in haematological tumor models.\u00a0Cancer Res\u00a0<\/em>2020;80:3077.<\/li>\r\n \t
  2. Li, C. et al.<\/em> A phase 1 study evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of Bcl-2 inhibitor BGB-11417 in adult patients with mature B-cell malignancies. Poster presentation at ASCO 2023; abstract 7558.<\/li>\r\n \t
  3. Soumerai, J. D. et al.<\/em> A phase 1 study with the novel B-cell lymphoma 2 inhibitor BGB-11417 as monotherapy or in combination with zanubrutinib in patients with non-Hodgkin lymphoma or Waldenstr\u00f6m macroglobulinemia: preliminary data. Poster presentation at ASH 2022; abstract 4201.<\/li>\r\n \t
  4. Shortt, J. et al.<\/em> Preliminary safety and efficacy of BGB-11417, a novel Bcl-2 inhibitor, in combination with azacitidine in patients with acute myeloid leukemia. Poster presentation at ASH 2022; abstract 1443.<\/li>\r\n \t
  5. Quach, H. et al.<\/em> Sonrotoclax (BGB-11417) in combination with dexamethasone for the treatment of relapsed\/refractory multiple myeloma with t(11;14): safety, efficacy, and determination of recommended phase 2 dose. Oral presentation at ASH 2023; abstract 1011.<\/li>\r\n \t
  6. Tedeschi, A. et al.<\/em> Monotherapy with second-generation BCL2 inhibitor sonrotoclax (BGB-11417) is well tolerated with high response rates in patients with relapsed\/refractory marginal zone lymphoma: data from an ongoing phase 1 study. Poster presentation at ASH 2023; abstract 3032.<\/li>\r\n \t
  7. Opat, S. et al.<\/em> A phase 1 study with the novel BCL2 Inhibitor BGB-11417 as monotherapy or in combination with zanubrutinib in patients with B-cell malignancies: preliminary data. Poster presentation at EHA 2022; abstract P687.<\/li>\r\n \t
  8. Cheah, C. Y. et al. <\/em>A phase 1 study with the novel B-cell lymphoma 2 (Bcl-2) inhibitor BGB-11417 as monotherapy or in combination with zanubrutinib in patients with CLL\/SLL: preliminary data. Oral presentation at ASH 2022; abstract 962.<\/li>\r\n<\/ol>","mechanism_of_action":"The B-cell lymphoma 2 (BCL2) gene family encodes more than 20 proteins that regulate the intrinsic apoptosis pathway, and are fundamental to the balance between cell survival and cell death.1<\/sup>\r\n\r\nAcquiring resistance to apoptosis is a highly regulated process, characteristic of both hematologic malignancies and solid tumors.1,2<\/sup>\u00a0Anti-apoptotic BCL2 has been shown to promote malignant cell survival by attenuating apoptosis. The dysregulation of\u00a0BCL2\u00a0<\/em>results in overexpression of the anti-apoptotic protein BCL2 which alters the balance of pro-apoptotic members of the BCL2 family. In normal cells, cell death signals trigger BID and BIM to activate BAX and BAK. Oligomerization of the pro-apoptotic proteins BAX and BAK, results in mitochondrial outer membrane permeabilization (MOMP), the release of cytochrome\u00a0c<\/em>\u00a0and second mitochondria-derived activator of caspase (SMAC) from the mitochondria and the subsequent activation of caspases resulting in cell death.1<\/sup>\r\n\r\nAnti-apoptotic BCL2 sequesters pro-apoptotic proteins such as BAX and BAK by binding to their BH3 motifs leading to inhibitions of the intrinsic apoptosis pathway.1<\/sup>\r\n\r\nSonrotoclax acts as a BH3 mimetic. By binding to BCL2, it induces BAX-BAK-dependent apoptosis. BCL2 is a well-validated target for B-cell malignancies. With long term treatment, recurrent mutation of G10V in BCL2 has been reported to mediate resistance to BCL2 inhibitors. In pre-clinical studies, sonrotoclax potently inhibited both wildtype and G10V-mutated BCL2.3<\/sup>\r\n\r\n\"\"\r\n\r\nReferences<\/strong>\r\n
      \r\n \t
    1. Ashkenazi, A., Fairbrother, W. J., Leverson, J. D. & Souers, A. J. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors.\u00a0 Rev. Drug Discov\u00a0<\/em>2017;16: 273\u2013284.<\/li>\r\n \t
    2. Montero, J. & Letai, A. Why do BCL-2 inhibitors work and where should we use them in the clinic?\u00a0Cell Death Differ\u00a0<\/em>2018;25:56\u201364.<\/li>\r\n \t
    3. Hu, N.\u00a0et al.<\/em>Abstract 3077: Preclinical characterization of BGB-11417, a potent and selective Bcl-2 inhibitor with superior antitumor activities in haematological tumor models.\u00a0Cancer Res\u00a0<\/em>2020;80:3077.<\/li>\r\n<\/ol>","approval_status":"Sonrotoclax\u00a0is an investigational compound for which safety and efficacy have not been established.\u00a0Because of the uncertainty of clinical trials, there is no guarantee that sonrotoclax will receive regulatory approval and become commercially available for the uses being investigated.<\/em>\r\n\r\nFor a complete list of sonrotoclax monotherapy and combination clinical trials, view the\u00a0pipeline<\/strong><\/a>.","other_resources":[6753]},"_links":{"self":[{"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/compound\/6846","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/compound"}],"about":[{"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/types\/compound"}],"acf:post":[{"embeddable":true,"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/posts\/6753"}],"acf:term":[{"embeddable":true,"taxonomy":"post-tag","href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/post-tag\/537"}],"wp:attachment":[{"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/media?parent=6846"}],"wp:term":[{"taxonomy":"post-tag","embeddable":true,"href":"https:\/\/beonemedaffairs.com\/us\/wp-json\/wp\/v2\/post-tag?post=6846"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}