hepatocellular carcinoma (hcc)

Palbociclib (PD 0332991) is a CDK inhibitor that inhibits CDK4 and CDK6 (IC50=11 16 nM) and is orally active. Palbociclib has anti-tumorigenic activity and has investigational potential for use in ER-positive and HER2-negative breast cancer.

Triglycidyl isocyanurate (Teroxirone) is a triazene triepoxide with antineoplastic and antiangiogenic activity. It inhibits growth of human non-small cell lung cancer cells by activating p53. Triglycidyl isocyanurate alkylates and cross-links DNA, thereby inhibiting DNA replication. It induces cell apoptosis and can be used for cancer research[1][2]. Triglycidyl isocyanurate is also used in various polyester powder coatings in the metal finishing industry.

Silymarin (Silybin B) (Silybin B) is a polyphenolic flavonoid that extracts from the milk thistle or seeds of Silybum marianum. It is used in the prevention and treatment of liver diseases.

Rosiglitazone (BRL49653) is a PPARγ agonist, TRPC5 activator, and TRPM3 inhibitor with oral activity. Rosiglitazone is also a hypoglycemic agent and a thiazolidinedione insulin sensitizer.

Palbociclib monohydrochloride (PD 0332991 hydrochloride) is a selective inhibitor of CDK4 6 (IC50s: 11 16 nM). It exhibits no inhibition against a panel of 36 additional protein kinases.

Palbociclib Isethionate (PD 0332991 isethionate) is a selective inhibitor of CDK4 6 (IC50s: 11 16 nM). It exhibits no inhibition against a panel of 36 additional protein kinases.

2-(Chloromethyl)-4-(4-nitrophenyl)thiazole, a natural product derived from Astragalus propinquus, exhibits anticancer activity and has been shown to be effective in hepatocellular carcinoma (HCC) by inhibiting the M2 polarization of tumor-associated macrophages (TAM).

Tyroserleutide (YSL), a small molecular tripeptide isolated from porcine spleen degradation products, inhibits the growth and metastasis of human hepatocellular carcinoma (HCC) both in vitro and in vivo.

Miriplatin hydrate (SM-11355 (hydrate)) (MPT) is a novel platinum complex used in TACE that shows promise for the treatment of hepatocellular carcinoma (HCC). Miriplatin hydrate is a lipophilic platinum complex that can be easily suspended in Lipiodol and gradually releases active platinum compounds in tumor tissue.

Vacquinol-1 is an MKK4 activator, which rapidly and selectively induces glioma cell death.

Miriplatin (SM-11355) (SM-11355) is a platinum complex used in TACE that has promise for the therapy of hepatocellular carcinoma (HCC).

Paritaprevir free base(ABT-450) is an orally bioavailable, synthetic acylsulfonamide inhibitor of the hepatitis C virus (HCV) protease complex comprised of non-structural protein 3 and 4A (NS3 NS4A), with potential activity against HCV genotype 1. Upon administration, paritaprevir reversibly binds to the active center and binding site of the HCV NS3 NS4A protease and prevents NS3 NS4A protease-mediated polyprotein maturation. This disrupts both the processing of viral proteins and the formation of the viral replication complex, which inhibits viral replication in HCV genotype 1-infected host cells. NS3, a serine protease, is essential for the proteolytic cleavage of multiple sites within the HCV polyprotein and plays a key role during HCV ribonucleic acid (RNA) replication. NS4A is an activating factor for NS3. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family, and infection is associated with the development of hepatocellular carcinoma (HCC).

Droxinostat (NS 41080) is a selective HDAC inhibitor, primarily targeting HDACs 6 and 8 with IC50 values of 2.47 μM and 1.46 μM, respectively. It is over 8-fold more selective against HDAC3 and shows no inhibition for HDAC1, 2, 4, 5, 7, 9, and 10.

MNK8 (3-methyl-6-(naphthalen-1-yl)pyrimidine-2,4(1H,3H)-dione) is a potent STAT3 inhibitor that reduces the ability of STAT3 to bind to DNA and also has a good growth inhibition effect on liver cancer cells [1].

Adenosine 5’-methylenediphosphate is an inhibitor of ecto-5’-nucleotidase, also known as CD73, with a Kivalue of 37 nM.1It inhibits cAMP accumulation induced by adenosine 5’-monophosphate , adenosine 5’-diphosphate , or adenosine 5’-triphosphate but not adenosine in VA-13 human fibroblasts when used at a concentration of 100 μM. Adenosine 5’-methylenediphosphate reduces proliferation of U138MG glioma cells, as well as inhibits the invasion and migration of MHCC97H hepatocellular carcinoma (HCC) cells in a migration assay.2,3It increases tumor infiltration of CD3+CD8+T cells and reduces tumor growth in a K1735 murine melanoma model when administered at a dose of 400 μg/mouse.4 1.Bruns, R.F.Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosineNaunyn Schmiedebergs Arch. Pharmacol.315(1)5-13(1980) 2.Braganhol, E., Tamajusuku, A.S.K., Bernardi, A., et al.Ecto-5′-nucleotidase/CD73 inhibition by quercetin in the human U138MG glioma cell lineBiochim. Biophys. Acta1770(9)1352-1359(2007) 3.Shali, S., Yu, J., Zhang, X., et al.Ecto\5′\nucleotidase (CD73) is a potential target of hepatocellular carcinomaJ. Cell Physiol.234(7)10248-10259(2018) 4.Forte, G., Sorrentino, R., Montinaro, A., et al.Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanomaJ. Immunol.189(5)2226-2233(2021)

Ascrinvacumab (PF-03446962) is a highly humanized IgG2 monoclonal antibody against ALK-1 with a Kd value of 7 nM for human ALK1. It has an inhibitory effect on TGF-β and can be used to study hepatocellular carcinoma (HCC).

Pyruvate Carboxylase-IN-1 (compound 37), a natural analog of erianin, is a potent inhibitor of pyruvate carboxylase (PC), with inhibitory concentrations (IC50) of 0.204 μM and 0.104 μM in cell lysate-based and cell-based PC activity assays, respectively. This compound effectively inhibits PC enzymatic activity, contributing to its anticancer effects in human hepatocellular carcinoma (HCC) [1].

Caricotamide is a synthetic co-substrate that activates the human endogenous enzyme NRH:quinone oxidoreductase 2 (NQO2) with potential chemoadjuvant activity. When caricotamide is administered simultaneously with the prodrug tretazicar, NQO2 converts tretazicar to the bifunctional alkylating agent dinitrobenzamide, which is capable of forming a high degree of DNA interstrand cross-links, resulting in the inhibition of DNA replication and the induction of apoptosis. NQO2 has been found to be over-expressed in cancers such as hepatocellular carcinoma (HCC), colorectal and ovarian cancers.

2-Acetamidofluorene, a potent carcinogen, is utilized for the induction of hepatocellular carcinoma (HCC) and multiple primary tumors [1] [2].

DS89002333 is a potent, orally active PRKACA inhibitor (IC50: 0.3 nM).DS89002333 has shown good antitumor effects in a patient-derived xenograft model of FL-HCC expressing a DNAJB1-PRKACA fusion gene.DS89002333 can be used to study fibrotic hepatocellular carcinoma ( FL-HCC).

Nicotinamide-d4 is intended for use as an internal standard for the quantification of nicotinamide by GC- or LC-MS. Nicotinamide is an amide form of niacin, which is also known as vitamin B3, that can be biosynthesized in vivo or obtained through the diet. It is a precursor in the synthesis of the metabolic cofactor NAD+ and an inhibitor of sirtuin 1 (SIRT1; IC50 = <50 µM). Nicotinamide (10 µM) increases the activity of serine palmitoyltransferase (SPT) and the biosynthesis of ceramide, glucosylceramide, sphingomyelin, free fatty acids, and cholesterol in primary human keratinocytes. Nicotinamide (40 µM) induces apoptosis in SNU-398, SNU-739, and HepG2 hepatocellular carcinoma (HCC) cells, and it prevents the formation of neoplastic lesions in a diethylnitrosamine-induced mouse model of HCC. Unlike niacin, nicotinamide does not reduce plasma lipid levels or induce flushing.

VEGFR-2-IN-33 (Compound 4d), a potent VEGFR inhibitor with an IC50 value of 61.04 nM, demonstrates significant inhibition of HepG2 cell proliferation with an IC50 of 4.31 nM, and is utilized for hepatocellular carcinoma (HCC) research [1].

Codrituzumab (GC3) is a humanized antibody against the glypican-3 hepatocellular carcinoma protein that can be used in combination with sorafenib to study incurable advanced hepatocellular carcinoma (HCC).

Antitumor Agent-92, an Icaritin derivative, induces G0/G1 phase cell cycle arrest and promotes apoptosis. This compound shows promise for hepatocellular carcinoma (HCC) research [1].

MC-GGFG-AM-(10Me-11F-Camptothecin) serves as a linker-payload conjugate in the synthesis of ZW251, an antibody-drug conjugate (ADC) targeting human GPC3. ZW251 comprises a humanized IgG1 antibody linked to ZD06519, a novel camptothecin-based topoisomerase 1 inhibitor, through a maleimide-anchor and a cleavable glycyl glycyl phenylalanyl glycine (GGFG)-aminomethyl (AM) linker. ZW251 demonstrates strong affinity for GPC3 in both human and cynomolgus monkey cells, characterized by rapid internalization in GPC3-positive Hepatocellular Carcinoma (HCC) cell lines and induces bystander-mediated killing of GPC3-negative cancer cells [1].

Xylocydine is a novel Cdk inhibitor, which is an effective inducer of apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Xylocydine also strongly inhibits the activity of Cdk7 and Cdk9, in vitro as well as in cell cultures, that is temporally associated with apoptotic cell death in xylocydine-induced HCC cells. Xylocydine can effectively suppress the growth of HCC xenografts in Balb/C-nude mice by preferentially inducing apoptosis in the xenografts, whereas the drug did not cause any apparent toxic effect on other tissues.Xylocydine is a good candidate for an anti-cancer drug for HCC therapy.

Autophagy-IN-C1 is a cinchona alkaloid derivative containing urea. Autophagy-IN-C1 not only induces apoptosis but also blocks autophagy in hepatocellular carcinoma (HCC) cells.

LASSBio-2052, a derivative of N-acylhydrazone with antitumor activity against hepatocellular carcinoma (HCC), inhibits HCC cells HepG2 and Hep3B with IC50 values of 18 and 41 μM, respectively. LASSBio-2052 arrests the cell cycle at G2 M phase through downregulation of FOXM1 and induces apoptosis in HCC cells [1].

LASSBio-1911 acts as an effective inhibitor of HDAC6. It exhibits antitumor activity against hepatocellular carcinoma (HCC) cells with minimal impact on normal cells.

ARF(26–44), cell-permeable is an anti-tumor peptide derived from a specific amino acid sequence of the p14ARF tumor suppressor protein. It serves as an inhibitor of FoxM1, a forkhead box M1 transcription factor, and has demonstrated significant anti-tumor activity in the treatment of mouse hepatocellular carcinoma (HCC). This activity includes increasing apoptosis and reducing tumor cell proliferation and angiogenesis. ARF(26–44), cell-permeable is useful for research in cancer therapy.

FGFR4-IN-14 (Compound 27i) is a selective FGFR4 inhibitor with an IC50 of 2.4 nM, effectively inhibiting cell proliferation in V550L and N535K mutant strains. It shows IC50 values of 21 nM against Huh7 cells, 2.5 nM against BaF3 ETV6-FGFR4-V550L cells, and 171 nM against BaF3 ETV6-FGFR4-N535K cells. FGFR4-IN-14 demonstrates significant antitumor efficacy in the Huh7 xenograft model and is utilized in hepatocellular carcinoma (HCC) research [1].

MDL-800 is a SIRT6 modulator with antitumor activity for the study of hepatocellular carcinoma and non-small cell lung cancer.

HL23 is a histone deacetylase (HDAC) inhibitor that effectively targets hepatocellular carcinoma (HCC). It promotes acetylation at the TXNIP promoter and increases TXNIP expression, modulating potassium channel activity and inducing TXNIP-dependent potassium deficiency. Additionally, HL23 impedes HCC progression and spread, demonstrating greater potency when combined with Sorafenib than the Sorafenib and Vorinostat duo [1].

FAPI-4 FAPI-4 is a fibroblast activating protein (FAP) inhibitor, a FAPI ligand, which shows strong liver uptake in PET imaging of primary liver cancer hepatocellular carcinoma (HCC) and is commonly used in PET imaging for the study of cancer.

CHNQD-01255 is an orally active inhibitor of Arf-GEFs, demonstrating effectiveness against hepatocellular carcinoma (HCC).

Pyruvate Carboxylase-IN-2 is a natural analog of erianin. Pyruvate Carboxylase-IN-2 (compound 29) is a potent inhibitor of pyruvate carboxylase (PC). In cell lysate-based and cell-based PC activity assays, Pyruvate Carboxylase-IN-2 shows IC 50 s of 0.065 and 0.097 μM, respectively. Pyruvate Carboxylase-IN-2 mediates the anticancer effect in human hepatocellular carcinoma (HCC).

Rosiglitazone hydrochloride (BRL-49653 HCl) is a blood glucose-lowering drugs, stimulating insulin secretion by binding to the PPAR receptors in fat cells.

Glycochenodeoxycholic acid 3-glucuronide, a steroid glucuronide and plasma metabolite, can be utilized as a biomarker in diabetes and hepatocellular carcinoma (HCC) research [1].

WNTinib (APS-8-100-2), a multi-kinase inhibitor, selectively targets β-catenin (CTNNB1) mutated hepatocellular carcinoma (HCC) and impedes oncogenic Wnt signaling. It achieves this by inhibiting KIT MAPK and subsequent activation of EZH2 [1].

HBV-IN-23 (Compound 5k) is an inhibitor of HBV DNA replication with an IC50 of 0.58 μM, inhibiting both drug-sensitive and drug-resistant strains. It induces apoptosis in HepG2 cells and demonstrates anti-hepatocellular carcinoma (HCC) effects.

Nicotinamide Hydrochloride, a form of vitamin B3 (niacin), inhibits sirtuin 2 (SIRT2) activity in vitro with an EC50 of 2 μM, reducing melanoma cell number by up to 90% and increasing cellular NAD+, ATP, and ROS levels. It also inhibits tumor growth in vivo and improves survival in melanoma-bearing mice, making it useful for skin cancer research, including melanoma.

Nicotinamide ascorbate is a bioactive chemical.

Nicotinamide N-oxide (Nicotinamide 1-oxide) is recognized as an in vivo metabolite of nicotinamide which is a precurser of nicotinamide-adenine dinucleotide (NAD+) in animals. The enzyme that catalyzes the reduction of nicotinamide N-oxide to nicotinamide in the liver is xanthine oxidase.