Diffuse Large B-cell Lymphoma

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 EZH2 Degrader-42 (compound 57) is an EZH2-targeting PROTAC degrader and antiproliferative agent. PROTAC EZH2 Degrader-42 induces cIAP-mediated ubiquitination and subsequent proteasomal degradation of EZH2. PROTAC EZH2 Degrader-42 can be used for the research of lymphoma.

ISM-PR25 is an orally active PROTAC degrader targeting BTK, with a DC₅₀ of 0.04 nM in Ramos cells. ISM-PR25 degrades BTK protein via CRL4^CRBN E3 ligase-mediated ubiquitination. ISM-PR25 can be used for research on B-cell lymphoma.

ISM-PR44 is an orally active PROTAC degrader targeting BTK, with a DC₅₀ of 0.05 nM in BTK-HiBiT Ramos cells. ISM-PR44 recruits CRBN E3 ligase to induce ubiquitination and proteasomal degradation of BTK. ISM-PR44 exhibits antiproliferative and cytotoxic activities in B-cell lymphoma cells. ISM-PR44 can be used for research on B-cell lymphoma.

USP1-IN-20 is an orally effective and selective USP1 inhibitor with an IC₅₀ of 3.0 nM. USP1-IN-20 inhibits the USP1-UAF1 complex, leading to the accumulation of Ub-PCNA, which in turn induces DNA damage and G2/M phase arrest, while simultaneously promoting the degradation of the oncogenic protein c-MYC. USP1-IN-20 can be used for research on breast cancer and diffuse large B-cell lymphoma.

Truly-4 is a bifunctional Rpn13 PROTAC and CRBN ByeTAC degrader. Degradation of Rpn13 relies on CRBN-mediated E3 ubiquitin ligase activity, while degradation of CRBN itself proceeds via a ByeTAC mechanism of action. Truly-4 induces selective cytotoxicity in hematological cancer cells and solid cancer cells, but not in healthy cells, despite comparable levels of Rpn13 depletion in both cell types. Truly-4 can be used in studies related to B-cell lymphoma and triple-negative breast cancer.

EZH2-IN-25 is an EZH2 inhibitor that inhibits the catalytic subunit of PRC2. EZH2-IN-25 can be used for the research of diffuse large B cell lymphoma.

CDK9/EZH2-IN-2 is a potent dual CDK9 and EZH2 inhibitor with an IC₅₀ of 8.9 nM against EZH2. CDK9/EZH2-IN-2 inhibits anti-apoptotic proteins and induces DNA damage by blocking the activity of CDK9 and EZH2, ultimately leading to tumor cell apoptosis. CDK9/EZH2-IN-2 can be used for research on diffuse large B-cell lymphoma.

YL064 is a multi-target STAT3-c-MYC inhibitor that directly binds to ATXN3 and inhibits its deubiquitinating activity, thereby promoting the ubiquitination and proteasomal degradation of oncogenic substrates of ATXN3. YL064 inhibits the phosphorylation of STAT3-Tyr705 without altering the total protein level of STAT3; meanwhile, it directly binds to the SH2 domain of STAT3 to block the dimerization, nuclear translocation, and DNA-binding activity of STAT3. YL064 directly targets the C-terminal HLH-Zip domain of c-Myc, upregulates the phosphorylation of c-Myc at the Thr58 site, and induces the ubiquitination and proteasome-dependent degradation of c-Myc. YL064 suppresses tumor cell proliferation, induces G2/M cell cycle arrest, reduces cell migration and invasion capacities, and triggers cancer cell apoptosis. YL064 can be used in related research on breast cancer, prostate cancer, diffuse large B-cell lymphoma, and multiple myeloma.

BCL6-IN-10 is a molecular glue inhibitor targeting the BCL6 BTB domain with an IC₅₀ of 4 nM. BCL6-IN-10 blocks the interaction between BCL6 and transcriptional co-repressors, and induces partial degradation of BCL6 via the ubiquitin-proteasome pathway, thereby de-repressing BCL6 target genes and inhibiting cancer cell proliferation. BCL6-IN-10 can be used in the research of diffuse large B-cell lymphoma.

BCL6-IN-11 is a potent inhibitor of the BCL6 BTB domain and a partial degrader of BCL6. BCL6-IN-11 inhibits the interaction between the BCL6 BTB domain and BCOR with an IC₅₀ of 6 nM. BCL6-IN-11 can be used for research related to BCL6 degradation in diffuse large B-cell lymphoma (DLBCL).

rac-Lenalidomide-¹³C₅ (CC-5013-¹³C₅) is the ¹³C₅-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.

Lenalidomide-¹³C₅,¹⁵N (CC-5013-¹³C₅,¹⁵N) is the ¹³C, ¹⁵N-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.

Lisaftoclax-d₈ is the deuterated-labeled Lisaftoclax (HY-129179). 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.

PROTAC BRD4 Degrader-40 is a BRD4 PROTAC degrader. PROTAC BRD4 Degrader-40 binds to Cereblon and recruits the CRL4^CRBN E3 ubiquitin ligase complex, mediates BRD4 degradation via the ubiquitin-proteasome pathway, and does not induce the degradation of classic CRBN neo-substrates IKZF1 and IKZF3. PROTAC BRD4 Degrader-40 induces BRD4 degradation in cancer cells. PROTAC BRD4 Degrader-40 can be used in research related to diffuse large B-cell lymphoma and acute myeloid leukemia.

CCT373567 is a non-degrading isomer of the BCL6 degrader CCT373566 (HY-146185). CCT373567 acts as a BCL6 inhibitor with an IC₅₀ of 2.9 nM. CCT373567 exerts growth inhibitory activity against cancer cells expressing BCL6, but shows low activity against cancer cells with low BCL6 expression. CCT373567 can be used in research related to diffuse large B-cell lymphoma.

PROTAC BTK/IKZF1/3 Degrader-1 is an orally active PROTAC-IMiD bifunctional protein degrader that selectively degrades BTK, IKZF1 and IKZF3. PROTAC BTK/IKZF1/3 Degrader-1 recruits the CRBN E3 ubiquitin ligase to form a ternary complex, mediating ubiquitination and proteasome-dependent degradation of target proteins, with no obvious degrading effect on GSPT1. PROTAC BTK/IKZF1/3 Degrader-1 inhibits cancer cell proliferation, induces cancer cell apoptosis, and suppresses tumor growth. PROTAC BTK/IKZF1/3 Degrader-1 can be used for the research of diffuse large B-cell lymphoma.

PROTAC BCL6/IKZF1/3 Degrader-1 is an orally active bifunctional PROTAC‑IMiD protein degrader that targets and degrades BCL6, IKZF1 and IKZF3. PROTAC BCL6/IKZF1/3 Degrader-1 induces ubiquitination and proteasome-mediated degradation of target proteins by recruiting E3 ubiquitin ligase, and triggers cell cycle arrest and apoptosis. PROTAC BCL6/IKZF1/3 Degrader-1 exhibits favorable anti-tumor activity in diffuse large B-cell lymphoma xenograft models. PROTAC BCL6/IKZF1/3 Degrader-1 can be used for the research of diffuse large B-cell lymphoma.

Auristatin S TFA is a potent Auristatin payload. Auristatin S TFA binds to the vinca-binding site on tubulin, thereby inhibiting microtubule assembly and inducing cell cycle arrest and apoptosis. Auristatin S TFA acts as a cytotoxic component of antibody-drug conjugates (ADCs) and exerts target-specific cytotoxicity against cancer cells. Auristatin S TFA can be used in the research of lymphoma, anaplastic large cell lymphoma and Hodgkin lymphoma.

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.