Diffuse Large B-cell Lymphoma

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.

L18I is a Bruton's tyrosine kinase (BTK) PROTAC degrader that targets wild-type and BTK^C481, and recruits the cereblon E3 ligase to mediate proteasomal degradation. L18I regulates the BCR, TLR, FcγR and NLRP3 inflammasome signaling pathways, inhibits the phosphorylation of PLCγ-2, ERK1/2 and p38, and reduces the levels of B cell activation markers CD25, CD69 and CD86. L18I downregulates the NF-κB, TNF and TLR signaling pathways, reduces the production of pro-inflammatory cytokines, and decreases immune cell infiltration and immune complex deposition. L18I inhibits the proliferation of BTK-expressing lymphoma cells, induces tumor regression in xenograft models, and exhibits synergistic activity when combined with inhibitors of SYK, PI3K or Lyn. L18I can be used in research related to lupus, diffuse alveolar hemorrhage and B-cell lymphoma.

PROTAC BTK Degrader-16 is a BTK PROTAC degrader with a DC₅₀ of 0.0006 nM in TMD8 cells. PROTAC BTK Degrader-16 recruits E3 ligase CRBN to tag BTK for degradation, leading to loss of BTK signaling. PROTAC BTK Degrader-16 induces degradation of BTK, leading to inhibition of cell growth in ABC-DLBCL cells. PROTAC BTK Degrader-16 can be used for the research of activated b-cell-like diffuse large b-cell lymphoma (ABC-DLBCL).

PROTAC SMARCA2/4 degrader-38 is a SMARCA2/4 degrader (SMARCA2: DC₅₀ = 3.0 nM; SMARCA4: 4.0 nM). PROTAC SMARCA2/4 degrader-38 binds to SMARCA2 and SMARCA4 bromodomains to induce degradation via the ubiquitin-proteasome system. PROTAC SMARCA2/4 degrader-38 induces G₀/G₁ phase cell cycle arrest and cell apoptosis in hematological cancer cells, blocks oncogenic activity of MYC and other disease-related genes in acute myeloid leukemia cells and inhibits proliferation of hematological cancer cell lines. PROTAC SMARCA2/4 degrader-38 can be used for the research of acute myeloid leukemia, diffuse large B-cell lymphoma, breast cancer, ovarian cancer, colorectal cancer, liver cancer, lung cancer.

HG6-64-1 (HMSL 10017-101-1) is a B-raf kinase modulator.HG6-64-1 modulates B-raf kinase activity, including the V600E mutant form and the drug-resistant gatekeeper mutation T529I. HG6-64-1 is a germinal center kinase inhibitor. HG6-64-1 induces cell cycle arrest and apoptosis. HG6-64-1 can be used for the research of diffuse large B-cell lymphoma (DLBCL).

BLK degrader 1 is a selective B lymphoid tyrosine kinase (BLK) degrader with a BLK DC₅₀ of 49 nM in cells. BLK degrader 1 induces ubiquitin-proteasome-dependent BLK degradation through binding. BLK degrader 1 exhibits anticancer activity in multiple B lymphocyte cell lines and downregulates CDK2 protein levels. BLK degrader 1 can be used in research related to B cell lymphoma.

DZ-837 is a BCL6 PROTAC degrader with a DC₅₀ of 557.7 nM. DZ-837 induces BCL6 ubiquitination and degradation in a CRBN-dependent manner via the ubiquitin-proteasome system. DZ-837 activates CDKN1A and CDKN1B, the downstream genes of BCL6. DZ-837 upregulates p21 and p27 proteins. DZ-837 inhibits tumor growth in a diffuse large B-cell lymphoma xenograft mouse model. DZ-837 exerts synergistic antiproliferative effects when combined with Ibrutinib (HY-10997). DZ-837 can be used in studies related to diffuse large B-cell lymphoma.

MGD-28 is an orally effective cereblon-dependent molecular glue degrader that potently degrades CK1α, IKZF1, IKZF2, and IKZF3, with respective DC₅₀ values of 7.8, 3.8, 56.3, and 7.1 nM. MGD-28 also induces the degradation of multiple novel substrate proteins including ZFP91, DTWD1, ZNFX1, MBD1, and MBD3 via a CRBN/Cullin- and proteasome-dependent mechanism. MGD-28 induces cell apoptosis. MGD-28 is used in the research of multiple myeloma, acute myeloid leukemia, diffuse large B-cell lymphoma, and related malignancies.

Zavabresib (OPN-2853; PLX2853; BET-IN-16) is an orally active inhibitor of the BET family of proteins. Zavabresib blocks bromodomain-mediated interactions, reduces BRD4 enrichment at the regulatory regions of transcription factors in T cells, exerts tumor growth inhibitory effects, and enhances the efficacy of immunotherapy. Zavabresib is applicable to research on chronic lymphocytic leukemia, castration-resistant prostate cancer, diffuse large B-cell lymphoma, colon adenocarcinoma, and myelofibrosis.

Semustine is an orally active, blood-brain barrier permeable antitumor alkylating agent with a binding affinity of 1.53 × 10³ M^-1 for guanine and thymine residues in bovine DNA. Semustine undergoes major groove-directed alkylation at guanine residues to form O6-chloroethylguanine and N1-O6-ethanoguanine adducts, and generates dG-dC interstrand crosslinks. Semustine induces partial B- to C-type transition of DNA, base stacking and helical structure distortion, mild dehydration, as well as partial DNA double-strand unwinding. Semustine can be used in research related to Lewis lung cancer, leukemia, Hodgkin's lymphoma, malignant melanoma, glioma, and diffuse large B-cell lymphoma.

Amulirafusp alfa (IMM-0306) is a fusion protein of CD20 monoclonal antibody (mAb) with the CD47 binding domain of SIRPα, with human CD20 K_d 2.45 nM and human CD47 K_d 4.91 nM. Amulirafusp alfa binds to CD20 and CD47 on B cells, engages FcɣR, blocks CD47-SIRPα interaction, activates macrophages, NK cells, and complement cascade, mediates phagocytosis and cytotoxicity, inhibits apoptosis of Jurkat-CSR cells, reverses IL-16 tumor-promoting effects, and binds human/cynomolgus CD47 but not mouse/rat CD47. Amulirafusp alfa can be used for the research of hematological malignancies, relapsed or refractory CD20-positive B-cell non-Hodgkin’s lymphoma, relapsed or refractory B-cell non-Hodgkin lymphoma, and activated B-cell-like diffuse large B-cell lymphoma.

MGD-4 is an orally active cereblon-dependent molecular glue degrader with a phthalazinone scaffold. MGD-4 degrades the Ikaros family proteins IKZF1, IKZF2 and IKZF3 in a dose-dependent manner, with DC₅₀ values of 67.2 nM, 918.2 nM and 95.8 nM, respectively. MGD-4 exhibits weak degradation activity against CK1α. MGD-4 inhibits the viability of multiple myeloma (MM) and acute myeloid leukemia (AML) cells and induces cell apoptosis. MGD-4 is used for the research of multiple myeloma, acute myeloid leukemia, diffuse large B-cell lymphoma and related hematological malignancies .

Lenalidomide-d₅ (CC-5013-d₅) is the d₅-labeled Lenalidomide (HY-A0003). Lenalidomide (CC-5013) is an orally active immunomodulatory agent that binds CRBN as a molecular glue to alter substrate specificity, inducing ubiquitination and proteasome-dependent degradation of IKZF1, IKZF3 and CK1α. Lenalidomide induces apoptosis by degrading IKZF1/3, and activates p53 by degrading CK1α. Lenalidomide promotes IL-2 release and effector functions of CD8⁺ T/NK cells, while inhibiting TNF-α secretion and M1-type pyroptosis. Lenalidomide can be used in research related to hematological malignancies, acute liver failure and acute kidney injury.

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

PROTAC BCL6 Degrader-2 is an orally active, selective BCL6 PROTAC degrader (DC₅₀: 0.45 nM in HEK293T cells). PROTAC BCL6 Degrader-2 promotes ubiquitination and degradation of BCL6. It exhibits anticancer activity against BCL6-dependent diffuse large B-cell lymphoma. PROTAC BCL6 Degrader-2 can be used for the research of diffuse large B-cell lymphoma.

Lenalidomide hydrochloride (CC-5013 hydrochloride) is an orally active immunomodulatory agent that binds CRBN as a molecular glue to alter substrate specificity, inducing ubiquitination and proteasome-dependent degradation of IKZF1, IKZF3 and CK1α. Lenalidomide hydrochloride induces apoptosis by degrading IKZF1/3, and activates p53 by degrading CK1α. Lenalidomide hydrochloride promotes IL-2 release and effector functions of CD8⁺ T/NK cells, while inhibiting TNF-α secretion and M1-type pyroptosis. Lenalidomide hydrochloride can be used in research related to hematological malignancies, acute liver failure and acute kidney injury.

DBt-10 is a PROTAC degrader that targets and degrades BTK by recruiting DCAF1. It degrades BTK in TMD8 BTK-GFP/mCherry cells with a DC₅₀ of 137 nM. DBt-10 induces CRL4^DCAF1-dependent ubiquitination and proteasomal degradation of BTK, and retains BTK-degrading and antiproliferative activities in TMD8 cells that are resistant to CRBN-BTK PROTACs due to loss of CRBN expression. DBt-10 has a high survival window and exhibits extremely weak apoptosis-inducing effects on lymphoma cells. DBt-10 can be used for research on diffuse large B-cell lymphoma.

Civorebrutinib (WS-413) is a selective, orally active BTK and TEC inhibitor with an IC₅₀ of <100 nM for both targets. Civorebrutinib inhibits B cell activation. Civorebrutinib significantly suppresses the in vivo growth of diffuse large B-cell lymphoma cells. Civorebrutinib can be used for the research of diffuse large B-cell lymphoma.