Lipid II-10, an ionizable lipid with a pKa of 6.16, is utilized in the formulation of lipid nanoparticles (LNPs) featuring a bilayer structure.

Iso-A11B5C1 is an ionizable lipid. The iso-A11B5C1 LNP demonstrates a high level of muscle-specific mRNA delivery efficiency. exhibiting transfection efficiency comparable to the commercially available lipid SM-102, while considerably reducing inadvertent mRNA expression in main organs such as the liver and spleen.Additionally, study results show that intramuscular administration of mRNA formulated with iso-A11B5C1 LNP caused potent cellular immune responses, even with limited expression observed in lymph nodes.

Abd110 (compound 42i) is a PROTAC molecule derived from lenalidomide that specifically targets ATR kinase for degradation. This compound demonstrates remarkable selectivity, effectively reducing both ATR and phospho-ATR levels while sparing related DNA damage response kinases ATM and DNA-PKcs.

MS8847 represents a novel PROTAC molecule that selectively targets EZH2 for degradation by recruiting the VHL E3 ubiquitin ligase complex. This compound mediates potent, proteasome-dependent elimination of EZH2, demonstrating significant anti-proliferative effects against both AML and TNBC cell lines.

THAL-SNS-032 is a novel CDK9 degrader PROTAC consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative that binds the E3 ubiquitin ligase Cereblon (CRBN).

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.

KT-253 is a potent small molecule that stabilizes p53 while simultaneously acting as a PROTAC to degrade MDM2 (DC50 = 0.4 nM). It demonstrates strong antiproliferative effects in RS4;11 leukemia cells (IC50 = 0.3 nM), inducing G2/M cell cycle arrest and apoptosis. In vivo studies confirm its antitumor activity in mouse models.

KT-333 is a first-in-class molecular glue that induces ​selective degradation of STAT3 via the ubiquitin-proteasome system by simultaneously engaging ​STAT3 and the VHL E3 ligase. This novel mechanism enables potent ​STAT3 depletion with minimal off-target effects, demonstrating strong ​anti-tumor activity in hematologic malignancies.

BTK-IN-29 (compound 14) is an inhibitor of Btk.

PROTAC BRD4 Degrader-21 (Compound 74) is a potent and selective degrader of BRD4, demonstrating robust tumor growth suppression in mouse xenograft models. Its efficacy supports its potential as a promising candidate for anticancer drug development.

SD-436 is a highly potent and selective STAT3 degrader with DC50 of 0.1 nM in human PBMCs and displays >10,000-fold degradation selectivity for STAT3 over other STAT proteins.

SD-36 (STAT3 degrader SD-36) is a potent, selective STAT3 degrader (PROTAC), potently induces the degradation of STAT3 protein in vitro and in vivo.SD-36 is designed using an analogue of CRBN ligand lenalidomide and the STAT3 inhibitor SI-109, binds to recombinant STAT3 protein with Ki of 11 nM.SD-36 (250 nM) depleted >90% of STAT3 protein in MOLM-16 cells after 4 hr treatment and >50% of STAT3 protein in DEL, KI-JK and SU-DHL-1 cells after 7 hr treatment, also efficiently degraded STAT3 protein in murine cells.SD-36 displays extremely high cellular selectivity for degradation of STAT3 over other STATs.SD-36 effectively degrades both wild-type and mutated STAT3 proteins in cells, effectively degrades mutated STAT3 (D661Y, K658R mutant), also effectively degrades CRISPR-mutated homozygous Y705F mutant STAT3 protein in DLD-1/STAT3Y705F/Y705F cells.SD-36 displayed strong growth-inhibitory activities in a subset of leukemia and lymphoma cell lines (MOLM-16 cell line IC50, 35 nM), 100-fold more potent than SI-109.SD-36 (i.v. 25 mg/kg) effectively and selectively depletes STAT3 protein, achieves complete and long-lasting tumor regression in in mouse xenograft tumors.

KT-474 is a highly active and selective, orally bioavailable IRAK4 degrader being developed for the treatment of toll-like receptor (TLR)/interleukin-1 receptor (IL-1R)-driven immune-inflammatory diseases.

NX-2127 is a potent, selective, and orally bioavailable BTK degrader with Kd of 18 nM (for WT BTK), 45 nM (BTK C481S), 18 nM (BTK T474I), 44 nM (BTK M437R), 97 nM (BTK V416L), and 88 nM (BTK L528W), respectively. NX-2127 efficiently engages the intracellular ubiquitin-proteasome system to simultaneously bind both BTK and the CRBN E3 ubiquitin ligase complex, inducing polyubiquitination and proteasome-dependent degradation of BTK, IKZF1, and IKZF3.

ARV-110 is an orally active, specific androgen receptor (AR) PROTAC degrader. ARV-110 promotes ubiquitination and degradation of AR. ARV-110 can be used for the research of prostate cancer.

ARV471 is an orally bioavailable estrogen receptor-targeting (ER-targeting) PROTAC for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

YJ1206 is an orally bioavailable PROTAC compound that selectively degrades CDK12 and CDK13, demonstrating potent activity (IC50 = 12.55 nM) in VCaP cells. It induces DNA damage, triggers apoptosis, and drives tumor regression in treatment-resistant prostate cancer PDX models, highlighting its therapeutic potential.

endo-BCN-O-PNB is an alkyl/ether-based PROTAC linker that can be used in the synthesis of PROTACs.

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.

KH-103 is a highly potent, catalytically-driven glucocorticoid receptor (GR) PTORAC degrader, demonstrate excellent performance in passively preventing ligand-induced gene expression activation in the absence of partial agonistic transcriptional triggerin.

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.

DSPE-PEG14-COOH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

DSPE-PEG2-mal is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

Thalidomide-NH-PEG1-NH2 hydrochloride is a synthesized E3 ligase ligand-linker conjugate that incorporates the Thalidomide based cereblon ligand and a linker used in PROTAC technology.

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.

Z0933M is a potent S phase kinase-associated protein 1 (Skp1) inhibitor with Kd of 54 nM, potently inhibits Skp1-F-box protein-protein interactions with Ki value of 231 nM in FP-based in vitro competition assays.

Cis-AGB1 is a negative control for AGB1 . Exhibits no significant VHL binding affinity.

PROTAC BRD4 Degrader-13 (compound 9d) is a potent chimeric BRD4 degrader. PROTAC BRD4 Degrader-13 can be conjugated with STEAP1 and CLL1 antibodies to degrade the BRD4 protein in PC3 prostate cancer cells, with a DC50 of 0.025 nM and 6.0 nM, respectively.

MS40 is a cereblon (CRBN)-based proteolysis targeting chimera (PROTAC) degrader of the onco-target WD repeat domain 5 (WDR5) [1]. WDR5 is an integral component of the MLL/KMT2A lysine methyltransferase protein complex. The WDR5-binding component of MS40 is the selective inhibitor OICR-9429, and the CRBN-targeting moiety is the immunomodulatory drug pomalidomide. MS40 promotes degradation of WDR5 and the pomalidomide transcription factor neo-substrates IKZF1 and IKZF3.