a375 cell

Nicotinamide, a vitamin B3 derivative, is an inhibitor of SIRT1 (IC50=50-180 μM) and SIRT2 (IC50=2 μM). Nicotinamide can be used as a precursor of nicotinamide adenine dinucleotide or NAD+, which can be supplemented by dietary intake and can prevent or treat melanoglossia and pellagra.

Vorinostat (SAHA) is a pan-histone deacetylase (HDAC) inhibitor (IC50=10 nM) with inhibitory activity against HDAC1/2/3/6/7/11. Vorinostat has antitumor activity, induces cell differentiation, blocks the cell cycle and induces apoptosis.

Paclitaxel (Taxol) is a natural product and a microtubule polymer stabilizer. Paclitaxel has anti-tumor activity and causes cell death by inducing mitotic arrest, apoptosis, and cell autophagy.

Temozolomide (TMZ) is a DNA alkylating agent with blood-brain barrier permeability and oral activity. Temozolomide has antitumor activity and antiangiogenic activity, and also induces apoptosis and autophagy. Temozolomide is stable under acidic conditions and hydrolyzes under neutral or slightly alkaline conditions.

SKLB-163 acts by downregulating RhoGDI, activating JNK-1 signaling pathway and caspase-3, and reducing phosphorylated Akt and p44/42 MAPK.

(+)-JQ-1 (JQ1) is a specific, reversible BET bromine domain inhibitor that targets BRD4 (1/2) with IC50 values of 77/33 nM. (+)-JQ-1 induces cell autophagy and inhibits cell proliferation.

Etoposide (VP-16-213) is a topoisomerase II inhibitor that inhibits DNA synthesis by forming a complex with topoisomerase II and DNA (IC50=60.3 μM). Etoposide has antitumor activity and induces apoptosis and autophagy.

Ursolic acid (Prunol) is a natural product, a pentacyclic triterpene carboxylic acid extracted from Rhododendron caprifolium. Ursolic acid has anti-tumor, anti-inflammatory, anti-bacterial and hypoglycemic activities.

Sodium dichloroacetate (BCA) , a specific inhibitor of pyruvate dehydrogenase kinase (PDK) with IC50 values of 183 and 80 μM for PDK2 and PDK4 respectively, has been shown to derepress a mitochondrial potassium-ion channel axis, trigger apoptosis in cancer cells, and inhibit tumor growth.

Ribociclib (LEE011) is an orally available, and highly specific CDK4/6 inhibitor (IC50:10/39 nM).

Irinotecan (CPT-11), a derivative of camptothecin, is an inhibitor of DNA topoisomerase I (Topo I). Irinotecan has antitumor activity by preventing DNA strand reattachment through binding to the Topo I complex, resulting in double-stranded DNA breaks and cell death.

Mitoxantrone (mitozantrone) is an anthracenedione antibiotic with antineoplastic activity. Mitoxantrone intercalates into and crosslinks DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, resulting in DNA strand breaks and inhibition of DNA repair. Mitoxantrone is less cardiotoxic compared to doxorubicin.

RAF-IN-1 is a potent inhibitor of b/cRAF, acting on cRAF (IC50: 3.8 nM), bRAFwt (IC50: 36 nM), bRAFV600E (IC50: 29.4 nM) and inhibiting A375 and H358 cell lines carrying the bRAFV600E mutation with a GI50 of 3.4 and 2.9 nM.

CAY10784 (STAT3-IN-17) is a STAT3 inhibitor with antiproliferative and antitumor activities. CAY10784 showed antibacterial activity against Clostridium difficile.

Combretastatin A-1 is a potent microtubule inhibitor with anti-tumour and anti-vascular activity, acting through microtubule protein depolymerisation-mediated inactivation of AKT to inhibit the Wnt/β-catenin pathway, and can be used to study hepatocellular carcinoma.

Tunlametinib is a highly selective, orally bioavailable small molecule inhibitor of MEK1 and MEK2 kinases with a reported IC50 value of 1.9 nM for MEK1. Tunlametinib exerts its antitumor effects by blocking the oncogenic RAS-RAF-MEK-ERK signaling pathway, thereby inducing tumor cell cycle arrest and promoting apoptosis, Tunlametinib demonstrates strong inhibitory activity against various RAS/RAF-mutant cancer cells such as those harboring BRAF V600E or KRAS G12C mutations, shows synergistic effects in combination with BRAF/KRASG12C/SHP2 inhibitors and Docetaxel, and is used in targeted therapy for RAS/RAF-driven cancers including melanoma, colorectal cancer, and non-small cell lung cancer (NSCLC).

Tanespimycin (KOS 953) is an Hsp90 inhibitor (IC50=5 nM) and is selective. Tanespimycin depletes intracellular STK38/NDR1 and decreases STK38 kinase activity. Tanespimycin also downregulated stk38 gene expression.

JNK-IN-8 (JNK Inhibitor XVI) is an irreversible JNK1/2/4 inhibitor (IC50: 4.7/18.7/1 nM) with over 10-fold selectivity compared to MNK2 and Fms, and no inhibition of Met, c-Kit, or PDGFRβ in the A375 cell line.

DS03090629, an orally active MEK inhibitor, functions by competitively inhibiting MEK activity in the presence of ATP. This compound demonstrates strong binding affinity to both MEK and phosphorylated MEK, with dissociation constants (Kd) of 0.11 and 0.15 nM, respectively. It has shown efficacy in suppressing the proliferation of melanoma cell lines that overexpress BRAF mutations, achieving IC50 values of 74.3 and 97.8 nM for BRAF V600E and MEK1 F53L transfected A375 cells, respectively. DS03090629 is thus considered promising for anti-melanoma therapies.

HSP90-IN-32, a carboxy-terminus inhibitor of Hsp90C, exhibits antiproliferative activity in various cell lines including SKMel173, SKMel103, SKMel19, and A375, with IC50 values of 1.01 μM, 0.782 μM, 0.607 μM, and 1.413 μM, respectively. This compound holds potential for research in anticancer agents.

KL-465, a MAGE-A3 PROTAC degrader, effectively degrades MAGE-A3 in HeLa cells with a DC50 of 2 μM. It also inhibits the proliferation of MAGE-A3-positive cancer cells, specifically in HCT116, A375, and HeLa cell lines.

VEGFR-2-IN-59 (Compound 3h) is an inhibitor of VEGFR2 with an IC50 of 3.73 µM. It exhibits cytotoxicity in cancer cell lines A549, HT-29, A375, MCF7, and NHDF, with IC50 values of 20.91, 19.70, 9.63, 17.43, and 20.71 μM, respectively. VEGFR-2-IN-59 also inhibits tubular structure formation and demonstrates anti-angiogenic properties.

SR-2890 is a potent and highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitor with an IC50 of 4 nM for CK1δ. This compound inhibits melanoma A375 cell growth with an EC50 of 38 nM in MTT assays and possesses pharmacokinetic properties suitable for xenograft studies using human cancer cell lines.

B-Raf IN 17 (Compound 8e) is an effective, orally active type II multi-kinase inhibitor. It shows potent cellular inhibition against BRAFWT, VEGFR-2, and FGFR-1 in the A375 cell line, with IC50 values of 0.02, 0.18, and 1.65 μM, respectively. B-Raf IN 17 is applicable for cancer research.