Immunotherapy for Colorectal Cancer

MCB-36 is a pan-KRAS PROTAC degrader that recruits VHL, with a K_d value of approximately 1 pM against KRAS, and it does not affect KRAS transcription. MCB-36 continuously degrades various KRAS mutants, inhibits oncogenic KRAS signaling pathways, reduces p-ERK levels, and induces apoptosis, thereby suppressing the growth of KRAS-dependent cancer cells. In vivo, MCB-36 inhibits tumor growth, overcomes resistance to KRAS G12C inhibitors, remodels the tumor immune microenvironment and enhances immune cell infiltration. MCB-36 can be used in research related to colorectal cancer and lung cancer.

ERG245 is a selective amino acid aminotransferase (BCAT1) inhibitor with a human IC₅₀ of 0.5 nM. ERG245 enhances oxidative phosphorylation (OXPHOS) in CD8⁺ T cells by specifically inhibiting BCAT1 activity, thereby increasing the cytotoxicity of CD8⁺ T cells. ERG245 shows anti-inflammatory and anti-tumor activities. ERG245 can be used for the researches of cancer anf inflammation, such as colitis and colon cancer.

NR-V04 is a selective NR4A1 PROTAC degrader. NR-V04 forms a ternary complex with NR4A1 and the VHL E3 ligase, mediates proteasome-dependent degradation of NR4A1. NR-V04 induces tumor-infiltrating B cells and effector memory CD8⁺ T cells and reduces monocytic myeloid-derived suppressor cells in tumor microenvironments. NR-V04 can be used for the research of melanoma and colon cancer.

SB24011 is a STING modulator and a TRIM29-STING protein-protein interaction inhibitor. SB24011 blocks TRIM29-induced K48-linked specific ubiquitination by binding to STING, thereby upregulating intracellular STING protein levels. SB24011 enhances inflammatory cytokine expression and STING-mediated immune responses, and exhibits abscopal antitumor activity that promotes tumor regression and activates T cell infiltration. When combined with STING agonists or anti-PD1 antibodies, SB24011 synergistically enhances antitumor responses. SB24011 is suitable for research related to colon cancer and melanoma.

Bacopaside I is an orally active aquaporin AQP1 inhibitor and PKC modulator with neuroprotective and anticancer activities. Bacopaside I specifically blocks the water channel and cGMP-gated ion channel activities of AQP1 without affecting AQP4, thereby inhibiting the migration of colon cancer cells expressing AQP1. Bacopaside I activates the Akt pathway by interacting with PI3K, specifically inhibits MAO-A, effectively alleviates neuron necrosis and apoptosis induced by oxygen-glucose deprivation, reduces oxidative stress, and regulates the surface expression of neuroreceptors. When combined with Bacopaside II (HY-N6016), Bacopaside I significantly reduces the viability, proliferation and invasion ability of breast cancer cells, and binds to the pregnane X receptor (PXR). Bacopaside I is applicable to the research of colon cancer, breast cancer, vascular dementia, cerebral ischemia and other related diseases.

PD-L1-IN-12 is an orally active and potent selenium-containing small-molecule PD-L1 inhibitor (K_D = 9.06 nM). PD-L1-IN-12 can mediate the internalization of PD-L1 and strongly block hPD-1 and hPD-L1 interaction (IC₅₀ = 5.2 nM). PD-L1-IN-12 can be used in colorectal cancer immunology research.

NSC850143 is an antiproliferative agent. NSC850143 induces antiproliferative and cytotoxic effects in aggressive tumor cells. NSC850143 can be used in the research of cancers such as leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer.

HDAC1-IN-14 is an indole-based benzamide selective HDAC1 inhibitor with an IC₅₀ of 77 nM. HDAC1-IN-14 acts as an antiproliferative agent, with GI₅₀ values ranging from nanomolar to low micromolar levels in various cancer cells. HDAC1-IN-14 induces G0-G1 cell cycle arrest in colon cancer cells. HDAC1-IN-14 upregulates the expression of Caspase-3, Cyto-C and Bax, and downregulates the expression of AKT-1. HDAC1-IN-14 can be used in research related to leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer.

PROTAC PD-L1 degrader-2 is a PD-L1 PROTAC degrader with an IC₅₀ of 197.4 nM and a K_d of 301 nM. PROTAC PD-L1 degrader-2 induces PD-L1 endocytosis, drives degradation via the proteasomal and lysosomal pathways, and inhibits the PD-1/PD-L1 interaction. As an immune activator, PROTAC PD-L1 degrader-2 increases the levels of CD4⁺, CD8⁺, granzyme B and perforin. PROTAC PD-L1 degrader-2 can be used in studies related to colon cancer immunology.

E722-2648 is an inhibitor targeting the BCL9 and β-catenin complex with antitumor activity. E722-2648 blocks complex formation by disrupting the interaction between the two proteins, thereby inhibiting β-catenin-mediated transcriptional activity and downregulating the expression of WNT target genes. E722-2648 effectively inhibits tumor growth in colon cancer xenograft models and colorectal cancer mouse models. E722-2648 can be used for the research of colon cancer and colorectal cancer.

HM-279 is a potent and orally active ALK5 inhibitor with an IC₅₀ of 4.7 nM. HM-279 shows cross-reactivity with ALK7 (IC₅₀ = 6.8 nM), but HM-279 has fair to good selectivity against other TGF-β receptor family kinases, with 4.5-693-fold selectivity. HM-279 demonstrates antitumor activity in vivo through CD8⁺ T cell immunity. HM-279 can be used for the research of colon cancer.

INSP-0154 is a potent creatine kinase B (CKB)/creatine transporter (SLC6A8) inhibitor. INSP-0154 binds to the SLC6A8 occluded pocket, prevents creatine transport into cells, and protects SLC6A8 cysteine residue C144 from irreversible inactivation. INSP-0154 inhibits creatine uptake in mouse heart tissue. INSP-0154 can be used for the research of cancer.

Pim-1 kinase-IN-16 is a potent PIM-1 kinase inhibitor. Pim-1 kinase-IN-16 can inhibit cancer cells proliferation, induce necrosis and late apoptosis. Pim-1 kinase-IN-16 can be used for the research of cancer, such as prostate cancer, colon cancer, lung cancer.

AT1412 is a CD9-binding antibody. AT1412 binds to the tetraspanin protein CD9 and modulates CD9 function by enhancing T cell adhesion to endothelial cells (HUVECs) and transendothelial migration. AT1412 binds to B-ALL cell lines but not to T-ALL. AT1412 induces antibody-dependent cellular cytotoxicity in B-ALL cell lines. AT1412 binds to melanoma cells, B-ALL, gastric cancer, colorectal cancer, and pancreatic cancer cells ^[1] .