Diffuse Large B-cell Lymphoma

Rituximab is an anti-CD20 chimeric monoclonal antibody used for research of certain autoimmune diseases and cancer.

MRT-2359 is an orally active and selective GSPT1 molecular glue degrader, with a DC₅₀ of 5 nM. MRT-2359 induces CRBN/GSPT1 ternary complex formation to drive CRBN- and degron-dependent proteasomal GSPT1 degradation, with selectivity for wild-type GSPT1 over the GSPT1^G575N mutant. MRT-2359 disrupts protein translation, induces ribosome stalling, downregulates MYC family proteins and their transcriptional output, reduces proliferation, and induces apoptosis in cancer cells. MRT-2359 can be used for the research of non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), neuroendocrine lung cancer, high grade neuroendocrine cancers, diffuse large B-cell lymphoma, prostate cancer, and MYC-driven solid tumors.

Rituximab (anti-CD20) is an anti-CD20 chimeric monoclonal antibody used to treat certain autoimmune diseases and types of cancer.

Obinutuzumab (GA101) a Type II CD20 humanized IgG1 monoclonal antibody in development for non-Hodgkin lymphoma.

ARV-393 is a BCL6 PROTAC degrader. ARV-393 forms a complex with BCL6 and Cereblon, induces BCL6 ubiquitination, and mediates BCL6 degradation via the ubiquitin-proteasome system. ARV-393 enhances CD20 expression, interferon pathway activity and antigen presentation. ARV-393 induces tumor growth inhibition and regression. ARV-393 can be used in research related to non-Hodgkin's lymphoma, high-grade B-cell lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma and follicular lymphoma.

Blidarvetug is a veterinary monoclonal antibody targeting MS4A1/CD20, which can be used to study CD20-positive B-cell lymphoma in dogs.

DFCI-002-06 is an orally active dual-target HCK/BTK PROTAC degrader with DC₅₀ values for HCK and BTK of 1.3 and 4.5 nM respectively. DFCI-002-06 retains higher anti-tumor activity than the HCK/BTK dual-target inhibitor (HY-15805), inducing apoptosis in cancer cells. DFCI-002-06 can be used for the study of MYD88 mutant B-cell malignancies.

PROTAC BCL6 Degrader-4 is a potent PROTAC BCL6 degrader. PROTAC BCL6 Degrader-4 recruits CRBN E3 ligase machinery to promote ubiquitination and proteasomal degradation of BCL6. PROTAC BCL6 Degrader-4 can be used for the research of diffuse large B-cell lymphoma and related hematological malignancies.

Polatuzumab is a monoclonal antibody that targets CD79b on the surface of B cells. Polatuzumab can be used to synthesize the ADC Polatuzumab Vedotin (HY-132253), which has anti-tumor activity.

UNC6852 is a PRC2 PROTAC degrader, with a DC₅₀ value of 0.79 μM for EED (HeLa), 0.3 μM for EZH2 (HeLa), and 0.59 μM for SUZ12 (DLBCL). UNC6852 binds to the WD40 aromatic cage of EED and CRL2-VHL, inducing proteasomal degradation of EED, EZH2 and SUZ12. UNC6852 reduces the level of H₃K₂₇me₃ and exerts antiproliferative effects in cancer cells. UNC6852 can be used in studies related to diffuse large B-cell lymphoma, triple-negative breast cancer and prostate cancer.

Lisaftoclax is an orally active, selective BCL-2 inhibitor with a K_i of < 0.1 nM against human BCL-2. Lisaftoclax selectively binds to BCL-2, disrupts the BCL-2:BIM complex, and antagonizes the antiapoptotic function of BCL-2. Lisaftoclax induces BAX/BAK-dependent, caspase-mediated apoptosis, upregulates the pro-death proteins BIM and Noxa, and downregulates mitochondrial respiratory function and ATP production. Lisaftoclax can be used in the research of hematological malignancies including chronic lymphocytic leukemia, multiple myeloma, and diffuse large B-cell lymphoma.

BMS-986458 is a highly selective, orally active cereblon-based BCL6 PROTAC degrader and antitumor agent. BMS-986458 selectively degrades BCL6 by binding cereblon to the BTB domain of BCL6, thereby regulating the cell cycle, antiproliferative and interferon signaling pathways, and upregulating the expression and distribution of CD20. BMS-986458 modulates the phenotype of follicular helper T cells and reduces circulating tumor DNA levels. The combination of BMS-986458 with CD20xCD3 bispecific antibody also enhances the efficiency of T cell tumor infiltration and expansion. BMS-986458 induces regression of BCL6-positive tumors and prolongs survival, and it is suitable for research related to B-cell non-Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and relapsed/refractory lymphoma.

Anzurstobart (CC-95251; BMS-986351) is a CD47/SIRPα inhibitor with human SIRPα K_d of 0.0541 nM and human SIRPα IC₅₀ of 100 nM. Anzurstobart binds SIRPα at a CD47-overlapping site, blocks CD47-SIRPα interactions, inhibits CD47-SIRPα axis signaling, and binds across 6 prevalent human SIRPα haplotypes. Anzurstobart binds SIRPγ and inhibits CD47-SIRPγ interactions. Anzurstobart can be used for the research of non-Hodgkin's lymphoma, colorectal cancer, squamous cell carcinoma of the head and neck, diffuse large B-cell lymphoma, and advanced solid and hematologic malignancies.

Zomiradomide (KT-413) is an orally active IRAK4 PROTAC degrader with a DC₅₀ of 6 nM. Zomiradomide inhibits the NF-κB signaling pathway, while its molecular glue function mediates the degradation of Ikaros and Aiolos (with a DC₅₀ of 1 nM for both), activates the IFN-I signaling pathway, and selectively degrades IMiD substrates. Zomiradomide inhibits cancer cell proliferation and tumor growth. Zomiradomide can be used in research related to B-cell non-Hodgkin's lymphoma and diffuse large B-cell lymphoma.

TCIP3 is a bivalent molecular glue degrader that binds dually to p300/CBP and BCL6. TCIP3 redirects p300 and CBP, thereby activating programmed cell death genes that are normally repressed by the oncogenic driver gene BCL6. TCIP3 induces acetylation of BCL6 and histone tails, inhibits c-MYC transcription. TCIP3 can be used for the research of diffuse large B-cell lymphoma (DLBCL).

PROTAC BTK Degrader-1 is a selective, orally active BTK PROTAC degrader with a DC₅₀ of 5.8 nM. PROTAC BTK Degrader-1 induces ubiquitination and degradation of wild-type and mutant (C481S, T316) BTK proteins via the CRBN-mediated pathway. PROTAC BTK Degrader-1 exhibits anticancer activity against diffuse large B-cell lymphoma. PROTAC BTK Degrader-1 can be used in lymphoma-related research.

SGR-1505 is an oral small molecule MALT1 inhibitor with anti-proliferative and antitumor activity.SGR-1505 inhibits MALT1 enzymatic activity to modulate NF-κB pathway gene expression.SGR-1505 induces modulation of cell cycle, DNA damage, and apoptosis-related genes in in vivo tumor samples.SGR-1505 exerts tumorostatic and regressive activity in ABC-DLBCL xenograft models.SGR-1505 can be used for the research of activated B cell-like diffuse large B cell lymphoma, non-Hodgkin B-cell lymphomas, chronic lymphocytic leukemia, and mature B cell neoplasms.

JWZ-5-13 is a CDK7 PROTAC degrader. JWZ-5-13 inhibits the proliferation of cancer cells. JWZ-5-13 is applicable to the research of ovarian cancer, diffuse large B-cell lymphoma, acute T-lymphoblastic leukemia and non-small cell lung cancer.

CST626 is a PROTAC degrader targeting IAP, with DC₅₀ values of 0.7 nM, 2.4 nM and 6.2 nM against XIAP, cIAP1 and cIAP2, respectively. This compound recruits the VHL E3 ubiquitin ligase to form a heterotrimeric complex, thereby inducing ubiquitination and proteasomal degradation of the target proteins. CST626 also exhibits certain degrading activity against VHL30 and VHL19. CST626 inhibits the proliferation and induces apoptosis of various hematologic tumor cell lines, and its anti-tumor effect is further enhanced when used in combination with TNF-α. CST626 can be used in research related to multiple myeloma, acute myeloid leukemia and diffuse large B-cell lymphoma.

NBI-961 is a NEK2 catalytic inhibitor with human NEK2 IC₅₀ ~12-fold lower than FLT3. NBI-961 induces proteasomal degradation of NEK2. NBI-961 induces G2/mitosis arrest, apoptosis, and compromises viability in DLBCL cells and patient-derived cells. NBI-961 sensitizes DLBCL cells to doxorubicin and vincristine, and suppresses DLBCL tumor growth in mice. NBI-961 can be used for the research of diffuse large b cell lymphoma.