Lung adenocarcinoma

PARP1-IN-8 (N-(3-chlorophenyl)-3-(1-oxo-4-phenylphthalazin-2(1H)-yl)propanamide) is an effective inhibito of PARP1 (IC50 = 97 nM).

Silybin A is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silicristin, silidianin and others. Silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins. Silibinin has also demonstrated in vitro anti-cancer effects against human prostate adenocarcinoma cells, estrogen-dependent and -independent human breast carcinoma cells, human ectocervical carcinoma cells, human colon cancer cells, and both small and nonsmall human lung carcinoma cells.

Brigimadlin (BI 907828) is an orally active and highly potent E3 ubiquitin-protein ligase MDM2-p53 antagonist with antitumor activity.Brigimadlin can be used to study metastatic BTC, PDAC, lung adenocarcinoma, or bladder cancer.

PARP-1-IN-2 is a potent PARP1 inhibitor that crosses the blood-brain barrier (IC50: 149 nM).PARP-1-IN-2 showed significant antiproliferative activity against the human lung adenocarcinoma epithelial cell line A549 in cellular assays.PARP-1-IN-2 induced apoptosis in A549 cells.

BPI-9016M is an effective, orally active, and selective dual inhibitor of c-Met and AXL tyrosine kinases. It suppresses tumor cell growth, invasion, and migration of lung adenocarcinoma.

KY-05009 is a chemical compound that effectively suppresses TGF-β1-induced epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma cells, reduces TNIK protein expression and the transcriptional activity of Wnt target genes, and promotes apoptosis in cancer cells, displaying anti-cancer properties. Furthermore, it functions as an ATP-competitive Traf2- and Nck-interacting kinase (TNIK) inhibitor with a Ki of 100 nM.

GSK319347A is a selective and potent dual inhibitor of TBK1 and IKKε with potential anti-tumor activity and inhibition of IKK2 activity, which can be used in the study of bladder cancer and lung adenocarcinoma.

PARP1-IN-31 (compound 11f) is a PARP1 inhibitor with an IC₅₀ of 97 nM. It induces apoptosis and inhibits proliferation in lung cancer cell lines (e.g., A549), while upregulating caspase-3 and caspase-9, making it suitable for lung adenocarcinoma research.

UNBS3157 is a novel naphthalimide derivative that is non-hematotoxic and exhibits significant antitumor activity through DNA intercalation and the poisoning of topoisomerase IIalpha. Unlike Amonafide, a related naphthalimide compound that showed activity in Phase II breast cancer trials but did not proceed to Phase III due to dose-limiting myelotoxicity, UNBS3157 has a maximum tolerated dose 3-4 times higher and does not cause hematotoxicity in mice at effective antitumor doses. In vivo models, including (i) L1210 mouse leukemia, (ii) MXT-HI mouse mammary adenocarcinoma, and (iii) human A549 non-small cell lung carcinoma and BxPC3 pancreatic cancer orthotopic models, demonstrate superior efficacy of UNBS3157 compared to Amonafide.

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.

CDK2/FLT4/PDGFRA-IN-1 (Compound 4a) is a potent inhibitor of CDK2/cyclin A, FLT4 (VEGFR3), and PDGFRA, with IC50 values of 1.672, 0.554, and 0.629 μM respectively. This compound demonstrates significant antiproliferative effects on cancer cells, including lung cancer EBC-1, pancreatic ductal adenocarcinoma AsPC-1, and colorectal cancer HT-29 cells. Additionally, CDK2/FLT4/PDGFRA-IN-1 can induce apoptosis in these cancer cells.

PKM2-IN-10 is a PKM2 inhibitor. It effectively suppresses the proliferation of A549 and HCC1833 cell lines with IC50 values of 3.36 μM and 9.20 μM, respectively. PKM2-IN-10 demonstrates antitumor activity in human non-small cell lung cancer (NSCLC) and mouse lung adenocarcinoma models. It is applicable for research in lung cancer.

ALDH3A1-IN-4 is a selective ALDH3A1 inhibitor with an IC50 of 0.2 μM. ALDH3A1-IN-4 binds to the aldehyde-binding pocket of ALDH3A1 via hydrophobic interactions and van der Waals forces. ALDH3A1-IN-4 acts as a chemosensitizer that sensitizes ALDH3A1-expressing cancer cells to the antiproliferative effect of mafosfamide, but does not produce a sensitizing effect on non-cancer cells that do not express ALDH3A1. ALDH3A1-IN-4 is applicable to research related to lung adenocarcinoma and glioblastoma models, where ALDH3A1-IN-4 is used to investigate aldehyde dehydrogenase-dependent detoxification pathways, enzyme–ligand binding interactions, and differential cellular response mechanisms in tumor versus non-tumor cellular systems.

KMR-206 is a potent and selective PARP7 inhibitor with an IC50 of 13.7 nM. It enhances the expression of STAT1 and phosphorylated Tyr701 site STAT1 (pSTAT1). KMR-206 induces STING degradation and elevates type I IFN receptor levels, showing anticancer activity against lung adenocarcinoma and is applicable in colon cancer research.

PDK1-IN-5 is a selective inhibitor of PDK1 that reduces phosphorylation levels to activate PDH. This compound effectively reverses the Warburg effect by increasing acetyl-CoA, reducing lactate, elevating mitochondrial ROS, and subsequently inducing apoptosis, shifting cellular energy metabolism from glycolysis to oxidative phosphorylation. PDK1-IN-5 strongly inhibits tumor growth in vivo without causing systemic toxicity and can be used in research on lung adenocarcinoma, human non-small cell lung adenocarcinoma, gastric cancer, and colorectal cancer.

STAT3-IN-51 is a STAT3 inhibitor that binds directly to the SH2 domain of STAT3. This compound induces apoptosis, ferroptosis, and immunogenic cell death (ICD), enhancing antitumor immunity. It suppresses STAT3 activation (phosphorylation, p-STAT3) and its downstream signaling, while prompting reactive oxygen species (ROS) generation, decreasing Bcl-2 expression, disrupting mitochondrial functions, inhibiting GPX4 activity, and promoting lipid peroxidation. STAT3-IN-51 is applicable in research on colorectal cancer, breast adenocarcinoma, non-small cell lung cancer (NSCLC), and cisplatin-resistant lung adenocarcinoma.

XMU-MP-8 (SKPer1) is a potent molecular glue degrader that targets the oncogenic protein SKP2. It interacts with the F-box domain of SKP2 (Kd≈ 36 μM) and the N-terminal TPR domain of the E3 ligase STUB1 (Kd≈ 2.5 μM), leading to the formation of a stable SKP2-SKPer1-STUB1 ternary complex (Kd≈ 8.9 nM). This interaction triggers the ubiquitination and proteasomal degradation of SKP2. XMU-MP-8 selectively eradicates cancer cells expressing SKP2 and exhibits notable tumor-suppressive effects in vivo along with a favorable safety profile. It is applicable in research on cancers such as non-small cell lung adenocarcinoma (NSCLC) and prostate adenocarcinoma.

PROTACALK degrader-4 (Compound B8) is an ALKPROTAC degrader with a DC50 of 445.25 nM. It demonstrates significant antiproliferative activity against NCI-H2228 and NCI-H3122 cell lines. This compound causes a substantial downregulation of 390 proteins, including IGF-1R and its downstream proteins, such as ERK1/2 and STAT3. PROTACALK degrader-4 is applicable in lung adenocarcinoma research.

MMP-9-IN-14 is an MMP-9 inhibitor (IC50= 34.46 μM) that induces G1 phase cell cycle arrest and caspase-dependent apoptosis in cancer cells. It promotes the accumulation of phosphorylated γH2AX and inhibits the migration and invasion of cancer cells by downregulating the expression of MMP-2, MMP-9, and hTERT. In animal models, MMP-9-IN-14 suppresses tumor growth and angiogenic spreading. It is applicable in research on lung adenocarcinoma, cervical cancer, colorectal cancer, and other cancers.

MAT2A ligand 1 is a MAT2A inhibitor (IC50=29.5 nM) that acts as a PET tracer capable of crossing the blood-brain barrier. It is utilized for non-invasive imaging of tumors expressing MAT2A, exhibiting rapid tumor uptake equilibrium, high tumor-to-muscle ratio, and specific tumor-binding properties. MAT2A ligand 1 is applicable in research related to non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, glioblastoma, pancreatic adenocarcinoma, urothelial carcinoma, breast cancer, and prostate cancer.

ALK-IN-34, an anaplastic lymphoma kinase (ALK) inhibitor with an IC50 of 0.26 μM, demonstrates antiproliferative activity in lung cancer and gastric adenocarcinoma cells.

SHP2-IN-46 is an orally active SHP2 inhibitor (IC50= 11.76 μM) that suppresses SHP2 enzyme activity and demonstrates antitumor effects. It inhibits cell proliferation across various cancer cell lines and is applicable for research on lung adenocarcinoma, pancreatic cancer, and hepatoblastoma.

SPT-IN-2 is an orally bioavailable inhibitor of serine palmitoyltransferase (SPT), demonstrating an IC50 of 0.71 nM against human SPT2. This compound suppresses ceramide synthesis and cancer cell proliferation, while exhibiting anti-tumor efficacy, metabolic stability, and cell membrane permeability in xenograft mouse models. SPT-IN-2 efficiently blocks the de novo sphingolipid synthesis pathway, significantly reducing intracellular ceramide and 3-ketodihydrosphingosine (3-KDS) levels. It is applicable in research related to lung adenocarcinoma, acute promyelocytic leukemia, and breast cancer.

KRAS G12D-IN-32 (Page 158) is an inhibitor of KRAS G12D, which can be utilized in the research of adenocarcinoma, colorectal cancer, and non-small cell lung cancer.