| DC60470 |
TCIP1 |
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. |
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| DC72902 |
ARD-2051 |
ARD-2051 is a potent and orally active androgen receptor (AR) proteolysis-targeting chimera degrader. ARD-2051 achieves DC50 values of 0.6 nM for AR protein degradation in both the LNCaP and VCaP prostate cancer cell lines. ARD-2051 can be used for the research of prostate cancer. |
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| DC60530 |
BTK-IN-24(NX-5948)
Featured
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NX-5948,be also known as BTK-IN-24,is an oral BTK degrader.
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| DC65810 |
KT-333
Featured
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KT-333 is a molecular glues that degrades STAT3 protein. KT-333 mediates the selective degradation of STAT3 through the ubiquitin-proteasome system by binding to STAT3 protein and E3 ubiquitin ligase von Hippel-Lindau protein (VHL). KT-333 has strong selectivity for STAT3 protein degradation and good antitumor activity. KT-333 can be used in the study of hematologic malignancies such as large granular lymphocytic leukemia (LGL-L), peripheral T-cell lymphoma (PTCL), and cutaneous T-cell lymphoma (CTCL). |
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| DC74301 |
NX-1607
Featured
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NX-1607 (Compound 23) is an inhibitor of Cbl-b, an E3 enzyme in the ubiquitin-proteasome pathway, with an IC50 value of less than 1 nM. NX-1607 can be used in cancer research. |
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| DC74473 |
Thalidomide-O-PEG4-Acid |
Thalidomide-O-PEG4-Acid is a chemical linker for PROTAC design. |
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| DC74474 |
(R)-SL18 |
(R)-SL18 is a first-in-class, selective Annexin A3 (ANXA3) degrader, induces degradation of ANXA3 in MDA-MB-231 cells with DC50 value of 3.17 uM. |
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| DC74475 |
ARD-1676 |
ARD-1676 (ARD1676) is a highly potent and orally efficacious PROTAC degrader of the androgen receptor (AR) with DC50 values of 0.1 and 1.1 nM in AR+ VCaP and LNCaP cell lines, respectively. |
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| DC74476 |
BI 1810284 |
BI 1810284 (ACBI2, BI 01810284) is a potent, selective and orally bioavailable VHL-recruiting PROTAC degrader of SMARCA2 (DC50=1 nM in RKO cells), 30-fold selectivity over SMARCA4. |
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| DC74477 |
BJG-05-039 |
BJG-05-039 is a PAK1-selective degrader consisting of NVS-PAK1-1 conjugated to lenalidomide, a recruiter of the E3 ubiquitin ligase substrate adaptor Cereblon. |
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| DC74478 |
BSJ-04-146 |
BSJ-04-146 is a potent, selective FAK PROTAC (IC50=26 nM), induces potent and durable FAK degradation in pancreatic and breast cancer cell lines at 10 nM. |
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| DC74479 |
BSJ-05-037
Featured
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BSJ-05-037 is a potent and selective heterobifunctional degrader of ITK with DC50 of 17.6-41.8 nM in TCL lines DERL-2 and Hut78. |
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| DC74480 |
BTX-6654 |
BTX-6654 is a potent, selective SOS1 cereblon-based bifunctional PROTAC degrader, reduces downstream signaling markers, pERK and pS6, and displayed antiproliferative activity in cells harboring various KRAS mutations. |
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| DC74481 |
BWA-522 |
BWA-522 is a potent, orally bioavailable PROTAC degrader of the androgen receptor N-terminal domain (AR-NTD), induces AR-FL or AR-V7 protein degradationwith DC50 of 0.73 μM (AR-FL) and 0.67 μM (AR-V7) in VCaP cells. |
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| DC74482 |
CC-3240 |
CC-3240 is a molecular glue degrader of CaMKK2 based on CC-8977 with bingding IC50 of 9 nM and DC50 of 100 nM (THP1 cells, Dmax=92%). |
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| DC74483 |
Chk1 PROTAC-2 |
Chk1 PROTAC-2 is a potent Chk1 degrader with DC50 of 1.33 µM in A375 cells. |
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| DC74484 |
CRBN(BRAF)-24 |
CRBN(BRAF)-24 is a potent small molecule degrader against oncogenic BRAF V600E protein, potently degrades BRAFV600E in a ubiquitin–proteasome system (UPS)-dependent manner and inhibits the proliferation of BRAFV600E-driven cancer cells. |
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| DC74485 |
CRBN(FLT3)-8 |
CRBN(FLT3)-8 a highly potent FLT3 degrader by introducing gilteritinib into targeted protein degradation technology, potently degrades FLT3-ITD via UPS and inhibits the proliferation of FLT3-ITD mutant AML cells more effectively than gilteritinib. |
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| DC74486 |
DAS-5-oCRBN |
DAS-5-oCRBN is a potent and selective PROTAC for c-Src kinase with DC50 value of 3 nM, without effect on Bcr-Abl. |
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| DC74487 |
DAS-CHO-5-oCRBN |
DAS-CHO-5-oCRBN is a potent and selective PROTAC for c-Src kinase with DC50 value of 62 nM in CAL148 cells. |
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| DC74488 |
DB0614 |
DB0614 is a CRBN-based PROTAC, induces the degradation of NEK9, FAK, CDK4, CDK6, and WEE1 in cells. |
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| DC74489 |
DBt-10 |
DBt-10 is a potent BTK-specific DCAF1 PROTAC with TR-FRET IC50 of 136 nM, potently degrades BTK with DC50 of 137 nM in TMD8 BTK-GFP/mCherry cell-based assays. |
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| DC74490 |
dEALK1 |
dEALK1 is a small-molecule degrader of EML4-ALK fusion proteins with binding constant (Kd) value of 44 nM for kinase domain of recombinant ALK, overcomes resistance to ALK inhibitor ceritinib. |
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| DC74491 |
DeFer-2 |
DeFer-2 is an oleic acid (OA)-based ferritin-targeting PROTAC binding Kd of 17.1 uM, degrades ferritin and rapidly elevates the free iron content, induces pyroptosis. |
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| DC74492 |
Degradomer D-1 |
Degradomer D-1 is a selective proteasomal degrader of IRAK3 with Kd of 100 nM, DC50 of 94 nM, displays no binding affinity against IRAK4 (Ki >10 uM). |
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| DC74493 |
DU-14 |
DU-14 is a highly potent and selective small molecule degrader for both PTP1B and TC-PTP with DC50 values of 4.3 and 4.8 nM, respectively, in HEK293 cells after 16 hours treatment. |
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| DC74494 |
GNE-0011 |
GNE-0011 is a monovalent, JQ1-based BRD4 degrader that is not linked to an E3 ligase binder, triggers proteasomal and ubiquitin-dependent selective degradation of BRD4 over BRD2 and BRD3. |
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| DC74495 |
HDAC3 PROTAC P7 |
HDAC3 PROTAC P7 is a potent and selective HDAC3-directed PROTAC with IC50 of 40 nM (HDAC3 deacetylase activity), effectively induces HDAC3 degradation with DC50 of 0.6 nM in THP-1 cells (Emax=90%). |
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| DC74496 |
HJM-561 |
HJM-561 is a potent, selective and orally bioavailable EGFR PROTAC degrader, selectively degrades the EGFR C797S-containing triple mutants Del19/T790M/C797S and L858R/T790M/C797S with DC50 values of 9.2 nM and 5.8 nM, respectively. |
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| DC74497 |
HPP-9 |
HPP-9 is a potent BET bromodomain degrader that acts through a PROTAC mechanism, HPP-9 is a long-acting Hedgehog pathway inhibitor. |
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