C14-4 Core (Core 4) is the core structure of C14-4.

KRIBB3 is an Hsp27 and microtubule inhibitor that inhibits migration and invasion of MDA-MB-231 cells in vitro in an Hsp27-dependent manner.

E7090 (E 7090) is a highly potent and selective orally bioavailable inhibitor targeting FGFR1, FGFR2, and FGFR3, with IC50 values of 0.71 nM, 0.50 nM, and 1.2 nM, respectively. It exhibits significantly weaker inhibition of FGFR4, with an IC50 of 120 nM. This distinct selectivity profile positions E7090 as a promising therapeutic candidate for diseases driven by aberrant FGFR1-3 signaling, offering a targeted approach to inhibit these receptors while minimizing off-target effects on FGFR4. Its oral availability further enhances its potential as a convenient and effective treatment option for patients with FGFR-dependent conditions.

BMS-1166-N-piperidine-COOH, a derivative of the potent PD-1/PD-L1 interaction inhibitor BMS-1166, serves as a key component in the design of PROTAC PD-1/PD-L1 degrader-1 (HY-131183). By binding to an E3 ligase ligand via a linker, this moiety facilitates the targeted degradation of PD-1/PD-L1, offering a novel approach to modulate immune checkpoint pathways. BMS-1166 itself is a highly effective inhibitor of the PD-1/PD-L1 interaction, with an IC50 of 1.4 nM, and it counteracts the immune-suppressive effects of the PD-1/PD-L1 checkpoint on T cell activation. This innovative strategy combines the inhibitory potency of BMS-1166 with the degradation capability of PROTAC technology, providing a promising tool for advancing cancer immunotherapy and immune-related research.

JMV6944 is a potent agonist of the pregnane X receptor (PXR), demonstrating its ability to competitively inhibit the binding of the human PXR ligand-binding domain (LBD) with an IC50 value of 680 nM. This compound effectively induces the expression of CYP3A4 mRNA in freshly isolated primary human hepatocyte cultures, highlighting its role in modulating drug metabolism and detoxification pathways. JMV6944 serves as a valuable tool for investigating PXR-mediated transcriptional regulation and its implications in xenobiotic metabolism, liver function, and therapeutic interventions. Its dual functionality as a PXR agonist and CYP3A4 inducer underscores its potential in both research and drug development.

BS-181 is a highly selective inhibitor of CDK7, exhibiting potent activity with an IC50 value of 21 nM. It demonstrates remarkable specificity, showing over 40-fold greater selectivity for CDK7 compared to other cyclin-dependent kinases, including CDK1, CDK2, CDK4, CDK5, CDK6, and CDK9. This exceptional selectivity positions BS-181 as a valuable tool for studying CDK7-specific biological functions and exploring its therapeutic potential in diseases where CDK7 plays a critical role, such as cancer. Its precision in targeting CDK7 underscores its utility in both research and drug development efforts.

I-152 is a novel conjugate composed of N-acetyl-cysteine (NAC) and cysteamine (MEA), designed to harness the synergistic effects of these two bioactive compounds. It demonstrates the ability to activate key cellular signaling pathways, including NRF2 and ATF4, which are involved in oxidative stress response and cellular homeostasis. Additionally, I-152 exhibits potent anti-proliferative properties, making it a promising candidate for research in conditions characterized by uncontrolled cell growth, such as cancer. This unique combination of NAC and MEA in I-152 offers a multifaceted approach to modulating cellular pathways and addressing pathological processes.

KAT modulator-1 (Compound 3) is a novel modulator of lysine acetyltransferases (KATs) with a unique mechanism of action. It specifically interacts with the full-length p300 protein but does not engage with its isolated catalytic domain, highlighting its distinctive binding properties. This compound serves as a valuable tool for epigenetics research, enabling the exploration of p300's role in chromatin remodeling, gene regulation, and other epigenetic processes. Its selective interaction with full-length p300 offers insights into the structural and functional complexities of KATs, paving the way for the development of targeted epigenetic therapies.

Sovleplenib is a highly potent inhibitor of spleen tyrosine kinase (Syk), derived from the innovative research disclosed in patent WO2012167733 A1. This compound demonstrates significant potential in modulating Syk-mediated signaling pathways, offering a promising therapeutic approach for conditions where Syk activity plays a critical role. Its development underscores the ongoing advancements in targeted kinase inhibition, providing a valuable tool for both research and potential clinical applications in immune-related and inflammatory diseases.

TP0427736 is a highly selective inhibitor of ALK5, demonstrating potent activity with an IC50 of 2.72 nM. It effectively suppresses Smad2/3 phosphorylation in A549 cells, highlighting its ability to modulate TGF-β signaling pathways. Additionally, TP0427736 has been shown to reduce the growth inhibition of human outer root sheath cells, suggesting its potential therapeutic utility in conditions where ALK5-mediated signaling plays a critical role. This compound represents a promising tool for investigating ALK5-related biological processes and developing targeted treatments for diseases involving aberrant TGF-β signaling.

3-Succinylated cholic acid (3-sucCA) is a microbially derived bile acid that plays a significant role in gut health and metabolic regulation. As a lumen-restricted metabolite, 3-sucCA has been shown to mitigate the progression of metabolic-associated fatty liver disease (MAFLD) to metabolic-associated steatohepatitis (MASH) in mouse models. Its protective effects are primarily attributed to its ability to reshape the gut microbiota, particularly by enhancing the growth of Akkermansia muciniphila, a beneficial bacterium associated with improved metabolic health. Notably, patients with biopsy-confirmed MAFLD exhibit reduced levels of 3-sucCA, underscoring its potential as a biomarker and therapeutic target for managing metabolic liver diseases. This unique metabolite highlights the intricate interplay between gut microbiota and liver health, offering promising avenues for intervention.

FBnG is a key component of the non-ribosomal peptide synthetase/polyketide synthase (NRPS/PKS) machinery, playing a crucial role in the biosynthesis of fabrubactin (FBN). This versatile molecule can be utilized in the synthesis of AUTAC4, specifically as part of the compound FBnG-(Cys-acetamide)-CH2-PEG3-CH2-CH2-CH2-NH2 (HY-150408). By leveraging its integration into this synthetic pathway, FBnG serves as a valuable building block for the development of AUTAC4, highlighting its potential in advancing research and therapeutic applications related to targeted protein degradation and related biological processes.

BBO-8520 represents a groundbreaking first-in-class covalent inhibitor that uniquely targets both the active (ON) and inactive (OFF) states of KRAS-G12C. Through comprehensive global cysteine proteome analysis, BBO-8520 demonstrates exceptional binding specificity to KRAS-G12C, showcasing a remarkable selectivity of over 100-fold compared to wild-type KRAS and other mutant isoforms. Notably, BBO-8520 exhibits no detectable activity against N-RAS or H-RAS, underscoring its precision in selectively inhibiting KRAS-G12C. This distinctive profile positions BBO-8520 as a promising therapeutic candidate for addressing KRAS-G12C-driven cancers, offering a novel approach to targeting this historically challenging oncogenic mutation.

N4-Acetylcytidine triphosphate sodium serves as an efficient substrate in T7 Polymerase-driven in vitro transcription reactions, demonstrating its ability to be successfully incorporated into various templates. This modified nucleotide offers a unique advantage in expanding the scope of RNA synthesis, enabling the production of acetylated RNA molecules with potential applications in research and therapeutic development. Its compatibility with T7 Polymerase highlights its utility in generating tailored RNA constructs, providing researchers with a versatile tool for exploring RNA modifications and their functional implications.

N4-Acetylcytidine triphosphate is efficiently used as a substrate in T7 Polymerase-catalyzed in vitro transcription and can be incorporated into multiple templates.

MK-0752 is a moderately potent γ-secretase inhibitor, it is used as a head group of MK16 which is a a novel blood-brain barrier (BBB)-crossing lipid nanoparticle (BLNP) platform developed for efficient mRNA delivery to the central nervous system (CNS).

NCATS-SM7270 is a highly specific small molecule inhibitor of NADPH oxidase 2 (NOX2), exhibiting an IC50 value of 2.1 µM in polymorphonuclear leukocytes (PMN). It effectively inhibits NOX2 activity in both primary human and mouse granulocytes, demonstrating its targeted and potent mechanism of action.

Endosidine 5 (ES5), is one of the most potent small molecules interferes with recycling endosomes through Annexin A6, thereby promoting the release and expression of mRNA into the cytoplasm. The delivered mRNAs is greatly enhanced via inhibition of endocytic recycling in cells and in live mice. NAV2729 (NAV) and endosidin 5 (ES5), resulted in significant enhancement (1.5–2 folds) of LNP-mediated delivery of Fluc mRNAs. Incubation of NAV and ES5 together caused modest further increases in Fluc expression in comparison to the sole application of either compound.

ART558 is a nanomolar potent, selective, low molecular weight, allosteric DNA polymerase activity of Polθ inhibitor (IC50=7.9 nM). Inhibition of TMEJ with ART558 increases the efficiency of HDR-mediated repair on Cas9-induced DSBs, most profoundly in combination with a NHEJ/DNA-PKcs inhibitor.

Bropirimine is a synthetic agonist for toll-like receptor 7 (TLR7). Bropirimine inhibits differentiation of osteoclast precursor cells into osteoclasts via TLR7-mediated production of IFN-β. Bropirimine is an orally active immunomodulator that has demonstrated anticancer activity in transitional cell carcinoma in situ (CIS) in both the bladder and upper urinary Bropirimine could enhance the transfection efficiency to 2-fold to 5-fold of Lipofectamine 3000 and LNP, all of which are currently approved for clinical use in the treatment of the most common malignant tumors.

SCH 58261 is a potent and selective A2a adenosine receptor antagonist with Ki of 2.3 nM and 2 nM for rat A2a and bovine A2a. SCH58261 could enhance the transfection efficiency to 2-fold to 5-fold of Lipofectamine 3000 and LNP, all of which are currently approved for clinical use in the treatment of the most common malignant tumors.

HSL119 is a highly effective and selective inhibitor of hormonally upregulated neu-associated kinase (HUNK), demonstrating complete suppression of HUNK kinase activity at a concentration of 1 µM in biochemical assays. This compound highlights its precision and potency in targeting HUNK.

SH-BC-893 is a water-soluble, orally bioavailable synthetic sphingolipid that triggers nutrient transporter internalization and also blocks lysosome-dependent nutrient generation pathways in cancer cells, activates protein phosphatase 2A (PP2A), leading to mislocalization of the lipid kinase PIKfyve; selectively kills cells expressing an activated form of the anabolic oncogene Ras in vitro and in vivo.SH-BC-893, increases the activity of antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) up to 200-fold in vitro without permeabilizing endosomes. SH-BC-893 treatment trapped endocytosed oligonucleotides within extra-lysosomal compartments thought to be more permeable due to frequent membrane fission and fusion events. Simultaneous disruption of ARF6-dependent endocytic recycling and PIKfyve-dependent lysosomal fusion was necessary and sufficient for SH-BC-893 to increase non-lysosomal oligonucleotide levels and enhance their activity. In mice, oral administration of SH-BC-893 increased ASO potency in the liver by 15-fold without toxicity. More importantly, SH-BC-893 enabled target RNA knockdown in the CNS and lungs of mice treated subcutaneously with cholesterol-functionalized duplexed oligonucleotides or unmodified ASOs, respectively. Together, these results establish the feasibility of using a small molecule that disrupts endolysosomal trafficking to improve the activity of oligonucleotides in extrahepatic tissues.

NAV 2729 (NAV2729) is a chemical potentiator for mRNA-LNPs, increasing the delivery efficiencies of mRNA-LNPs in vitro and in vivo.

AZD-7648 is a potent and selective DNA-PK inhibitor. AZD7648,enhances HDR efficiency in CRISPR-Cas9 gene editing by shifting DNA repair from the error-prone NHEJ pathway to the precise HDR pathway, significantly improving gene targeting outcomes in human cells for effective ex vivo gene therapies.