phenotypes

Hepln-13 is a hepsin inhibitor that acts by hindering prostate cancer bone metastasis.

Sabizabulin (ABI-231) is a potent, orally bioavailable α- and β-tubulin inhibitor that is active against melanoma and prostate cancer cell lines. Sabizabulin inhibits tumor growth and metastatic phenotypes of cervical cancer cells by targeting HPV E6 and E7 and is also being studied in prostate cancer.

BPDA2 is a highly selective and competitive SHP2 inhibitor, exhibiting IC50 values of 92.0 nM for SHP2, and 33.39 μM and 40.71 μM for SHP1 and SHP1B, respectively. This compound effectively downregulates mitogenic and cell survival signaling, including reducing expression of receptor tyrosine kinases (RTKs). Furthermore, BPDA2 suppresses SHP2-mediated signaling, leading to the inhibition of breast cancer cell phenotypes [1].

Cyclocreatine, a creatine analogue and substrate for creatine kinase, inhibits creatine metabolism and prostate cancer cell proliferation, improving cognitive, autistic and epileptic phenotypes in mouse models of creatine transporter deficiency (CTD).

BRD5631 is an autophagy enhancer that operates through an mTOR-independent pathway. It influences several cellular disease phenotypes associated with autophagy, such as protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in cellular homeostasis and disease. [1].

Equisetin, an N-methylserine-derived acyl tetramic acid isolated from the terrestrial fungus Fusarium equiseti NRRL 5537, functions as a Quorum-sensing inhibitor (QSI) that specifically attenuates QS-regulated virulence phenotypes in P. aeruginosa, presenting a potent lead for treating P. aeruginosa infections without hindering bacterial growth. This tetramate-containing natural product possesses antibiotic and cytotoxic properties, effectively inhibiting the growth of Gram-positive bacteria and HIV-1 integrase activity, yet it does not impact Gram-negative bacteria.

G923-0271 is a TDP-43 inhibitor that improves disease phenotypes in TDP-43 nematode models and reduces the overexpression of human TDP-43 at the cellular level, making it useful for studying diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

GTCpFE, a compound synthesized from Dimethyl fumarate (DMF) and Aspirin (ASA), inhibits IKKα/β in the NF-κB pathway, exhibiting anti-inflammatory activity by preventing p65 from entering the nucleus. It selectively inhibits cancer stem cell (CSC) activity by reducing the growth of mammospheres and the expression of the CD44+CD24- immune phenotype. Furthermore, GTCpFE targets breast cancer stem cells, crucial in aggressive cancer phenotypes that depend on NFκB and PGE2.

ABCA1 inducer 1, a non-lipid inducer of ABCA1, enhances ABCA1 expression in E3/4FAD mice expressing human APOE 3/4, augments the lipidation of apolipoprotein (APOE), and reverses various Alzheimer's disease (AD) phenotypes without increasing triglycerides.

Antibacterialagent 247 (compound 30b) is a bacterium (bacterial) antagonist that significantly inhibits the formation of biofilms by Pseudomonas aeruginosa (IC50=5.8 μM) and various virulence phenotypes. It also enhances the antibacterial activity of combined treatments with tobramycin and polymyxin B.

AKV-9 is a mutant Cu/Zn superoxide dismutase (SOD1) inhibitor that effectively suppresses SOD1-induced protein aggregation and demonstrates significant protective effects against SOD1-induced cytotoxicity in PC-12 cells, with an EC50 of 0.3 μM. AKV-9 also ameliorates amyotrophic lateral sclerosis (ALS)-related phenotypes and significantly prolongs survival in mouse models, making it suitable for ALS pathogenesis and targeted therapy research.

SBI-183 is an orally active QSOX1 inhibitor (Kd: 20 μM). It can inhibit the proliferation and invasion phenotypes of renal carcinoma cell lines, triple-negative breast cancer cell lines, lung adenocarcinoma cell lines, and pancreatic ductal adenocarcinoma. In vivo, SBI-183 suppresses tumor growth in two human renal cell carcinoma xenograft mouse models.

KK181N1 is a triazolide selective inhibitor of the karrikin (KAR) receptor KAI2 that binds non-covalently to the catalytic pocket of KAI2 and has no significant effect on the related receptor AtD14. KK181N1 selectively inhibits KAR-induced phenotypes in Arabidopsis.

ZH8965 is an orally active TAAR1-Gs/Gq agonist (EC50: 6.1/14.8 nM) that shows efficacy in alleviating antipsychotic-like phenotypes and cognitive deficits in an MK-801-induced psychosis model in mice. It is applicable for research related to schizophrenia.

Namptactivator-5 (compound C8) is a potent activator of nicotinamide phosphoribosyltransferase (NAMPT), with a KD value of 6.19 µM. This compound demonstrates cellular anti-aging effects by promoting NAD+ production in the brain and reducing markers and secretory phenotypes associated with aging. Namptactivator-5 holds potential for researching age-related diseases.

HDAC6-IN-44 (compound H10) is a selective HDAC6 inhibitor with an IC50 value of 8.97 nM. It can suppress idiopathic pulmonary fibrosis phenotypes and exhibits anti-fibrotic activity in the lungs. Additionally, HDAC6-IN-44 has been shown to inhibit fibrosis progression in a bleomycin-induced mouse model and demonstrates good metabolic stability, making it a promising candidate for idiopathic pulmonary fibrosis research.

TAU-IN-3 (Compound 2) is an orally active TAU inhibitor that suppresses the expression of the MAPT exon 10 DDPAC mutant gene in HeLa cells (IC50: 0.6 µM). It reduces the 4R/3R MAPT mRNA ratio in HeLa cells transfected with WT or DDPAC minigenes. TAU-IN-3 inhibits the insertion of endogenous MAPT exon 10 and the production of 4R tau protein. It modulates tau splicing in htau mice and improves associated behavioral phenotypes. TAU-IN-3 is useful for researching neurodegenerative diseases.

Ancitabine is an antitumour drug that improves Hailey-Hailey disease-related phenotypes in yeast models. It is metabolised to cytarabine in vivo and inhibits DNA synthesis, primarily used for treating acute leukaemia.

Huib32 is a potent small-molecule USP32 inhibitor with an IC₅₀ of 21.2 nM and high selectivity over closely related deubiquitinases (DUBs) including USP8/10/16, UCHL1, and OTUB2. It inhibits USP32 via reversible covalent binding to the active site Cys743, thereby increasing substrate ubiquitination, altering endosomal morphology, and producing biological phenotypes similar to USP32 knockout. It can be used in research on breast cancer, ovarian cancer, lung cancer, Alzheimer’s disease, Parkinson’s disease, and other diseases.

FOXM1-IN-3 is a potent inhibitor of FOXM1 and a weak inhibitor of PI3Kγ (IC50 of 3.5 μM). It reduces FOXM1 expression at both protein and mRNA levels, inhibiting downstream effectors CCNB1 and CDC25. FOXM1-IN-3 induces G2/M phase cell cycle arrest and apoptosis in colorectal cancer cells. It also impedes colony formation and cell migration abilities of these cells. Additionally, FOXM1-IN-3 targets cancer stem cell phenotypes in colorectal cancer cells, reducing the expression of stem cell markers. It suppresses tumor growth in zebrafish xenotransplant models, making it applicable for colorectal cancer research.

NCDM-32B, a novel potent and selective KDM4 inhibitor, impairs viability and transforms phenotypes of basal breast cancer.

SRI-29132 is potent; highly permeant of the blood-brain barrier; and selective for LRRK2 kinase activity, therefore effective in attenuating pro-inflammatory responses in macrophages and in rescuing neurite retraction phenotypes in neurons.

Quorum sensing is a regulatory process used by bacteria for controlling gene expression in response to increasing cell density.[1] This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production.[2] Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group) and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family.[3] C16:1-Δ9-(L)-HSL is a long-chain AHL that functions as a quorum sensing signaling molecule in strains of S. meliloti.[4],[5],[6],[7] Regulating bacterial quorum sensing signaling can be used to inhibit pathogenesis and thus, represents a new approach to antimicrobial therapy in the treatment of infectious diseases.[8] Reference：[1]. González, J.E., and Keshavan, N.D. Messing with bacterial quorum sensing. Microbiol. Mol. Biol. Rev. 70(4), 859-875 (2006).[2]. Gould, T.A., Herman, J., Krank, J., et al. Specificity of acyl-homoserine lactone syntheses examined by mass spectrometry. J. Bacteriol. 188(2), 773-783 (2006).[3]. Penalver, C.G.N., Morin, D., Cantet, F., et al. Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone with a double unsaturated side chain under methylotrophic growth conditions. FEBS Lett. 580(2), 561-567 (2006).[4]. Teplitski, M., Eberhard, A., Gronquist, M.R., et al. Chemical identification of N-acyl homoserine lactone quorum-sensing signals produced by Sinorhizobium meliloti strains in defined medium. Archives of Microbiology 180, 494-497 (2003).[5]. Gao, M., Chen, H., Eberhard, A., et al. sinI- and expR-dependent quorum sensing in Sinorhizobium meliloti. Journal of Bacteriology 187(23), 7931-7944 (2005).[6]. Marketon, M.M., Glenn, S.A., Eberhard, A., et al. Quorum sensing controls exopolysaccharide production in Sinorhizobium meliloti. Journal of Bacteriology 185(1), 325-331 (2003).[7]. Marketon, M., Gronquist, M.R., Eberhard, A., et al. Characterization of the Sinorhizobium meliloti sinR/sinI locus and the production of novel N-Acyl homoserine lactones. Journal of Bacteriology 184(20), 5686-5695 (2002).[8]. Cegelski, L., Marshall, G.R., Eldridge, G.R., et al. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 6(1), 17-27 (2008).

Quorum sensing is a regulatory process used by bacteria for controlling gene expression in response to increasing cell density. This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production. Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group) and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family. C18:1-δ9 cis-(L)-HSL is a long-chain AHL that may have antimicrobial activity and thus, might be used to inhibit pathogenesis by regulating bacerial quorum sensing signaling.