| DC60470 |
TCIP1
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TCIP1 is the most potent transcriptional/epigenetic CIP (chemical inducers of proximity) and specifically activates BCL6 target genes. TCIP1 kills diffuse large B cell lymphoma cell lines, including chemotherapy-resistant, TP53-mutant lines and exhibits cell-specific and tissue-specific effects. TCIP1 successfully killed large B cell lymphoma cell lines, including chemotherapy-resistant TP53-mutant lines and exhibited cell-specific and tissue-specific effects. The activation of apoptosis to cell death took place in just 72 hours.BCL6 is critical to the lymphatic system, and mice engineered without the BCL6 gene die of complex inflammatory reactions. BRD4 is heavily involved in genome function and stability across many processes. Concerns regarding utilizing these important gene expressions and how they might affect off-target healthy tissues were addressed in the study.TCIP1 acts in a context-specific manner requiring the expression of BRD4 and BCL6 to both be present in order to bind them and operate at a concentration that would occupy only a tiny fraction of the total BCL6 molecules.TCIP1 induced dramatic transcriptomic changes in the spleen, notably with an upregulation of the FOXO3 gene, which mirrored activity in the targeted cancer cells. Despite the significant transcriptomic changes in the spleen, TCIP1 was well tolerated without adverse effects, with no significant differences in mouse body weight and no noticeable abnormalities such as inflammatory infiltrates or apoptotic cells.
BCL6-BRD4 TCIP1 (TCIP1) is a potent BCL6-BRD4 transcriptional/epigenetic chemical inducer of proximity (TCIP) by covalently linking BCL6 binder BI-3812 to BRD4 ligand JQ1, selectively kills DLBCL cells with EC50 of 1.3 nM against KARPAS422 cell.
TCIP1 rapidly and robustly killed other DLBCL lines with high levels of BCL6, but JQ1 and BI3812 separately or together shows100–1,000-fold less-effective cell killing.
TCIP1 is 200–10,000-fold more potent in killing DLBCL cells than the degradation of BRD4 by dBET1 and/or degradation of BCL6 by BI3802.
TCIP1 induces a stable, cooperative protein-protein interaction between bromodomain 1 (BD1) of BRD4 and the BTB domain of BCL6.
TCIP1 shows affinity for intracellular ternary complex of BRD4 with Kd of 340 nM in TR-FRET assays.
TCIP1 induces G1/S and G2/M block in the cell cycle, TCIP1 (10 nM) represses MYC and its targets while activating pro-apoptotic genes in KARPAS422 cells.
TCIP1 kills diffuse large B cell lymphoma cell lines, including chemotherapy-resistant, TP53-mutant lines, at EC50 of 1-10 nM in 72 h and exhibits cell-specific and tissue-specific effects, capturing the combinatorial specificity inherent to transcription. |
| DC39826 |
Homo-PROTAC cereblon degrader 1
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Homo-PROTAC cereblon degrader 1, is a cereblon degrader. |
| DC39709 |
Lenalidomide-Br
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Lenalidomide-Br (Compound 41) is an analog of cereblon (CRBN) ligand Lenalidomide for E3 ubiquitin ligase, and is used in the recruitment of CRBN protein. Lenalidomide-Br can be connected to the ligand for protein by a linker to form PROTACs.
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| DC72756 |
JQAD1
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JQAD1 is a CRBN-dependent PROTAC that selectively targets EP300 for degradation. JQAD1 suppresses EP300 expression and the H3K27ac modification. JQAD1 induces apoptosis. JQAD1 can be used in research of cancer. |
| DC72103 |
CC-99282
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CC-99282 (Golcadomide) is an orally active cereblon (CRBN) E3 ligase modulator (CELMoD). Ikaros and Aiolos are degraded potently and specifically by CC-99282, which co-opts CRBN. |
| DC50038 |
PROTAC SGK3 degrader-1
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PROTAC SGK3 degrader-1 (SGK3-PROTAC1), is a potent SKG3 degrader based on PROTAC. PROTAC SGK3 degrader-1 (0.3 μM) induces 50% degradation of endogenous SGK3 within 2 hours, with maximal 80% degradation observed within 8 hours, accompanied by a loss of phosphorylation of NDRG1 (an SGK3 substrate). |
| DC48434 |
TD-165
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TD165(TD 165) is a PROTAC-based cereblon (CRBN) degrader that degrads Cav1.2α with the DC50 of 20.4 nM, comprising a cereblon (CRBN) ligand binding group, a linker and an von Hippel-Landau (VHL) binding group. |
| DC48373 |
dTAGV-1 TFA
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dTAGV-1 TFA is a potent and selective degrader of mutant FKBP12F36V fusion proteins. dTAGV-1 TFA can induce degradation of FKBP12F36V-Nluc in vivo. |
| DC48369 |
AGB1
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AGB1 is a fast, highly selective, and potent bump-and-hole (B&H)-PROTAC degrader for BromoTag. AGB1 exhibits degradation for Ab:Brd4BD2 L387A and Ab: BromoTag-Brd2 with pDC50s of 7.8 and 7.9. AGB1 exhibits binary affinity to VHL (Kd=125 nM). AGB1 exhibits favorable pharmacokinetic profile in mice with the DC50, 6 h of ∼13 nM. |
| DC47884 |
TLR4-IN-C34-C2-COOH
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TLR4-IN-C34-C2-COO is a linker that incorporates TLR4 inhibitor TLR4-IN-C34. TLR4-IN-C34 inhibits TLR4 in enterocytes and macrophages, and reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. |
