mc38

MSA-2 is an orally available non-nucleotide STING agonist. The non-covalent dimer of MSA-2 binds to STING with nanomolar affinity. It shows anti-tumor activity in syngeneic mouse tumor models, synergizes with anti-PD-1, stimulates tumor secretion of interferon-β, induces tumor regression, and has long-lasting anti-tumor immunity. [3]

Digitonin is a natural product of the glycoside family and is a detergent. Digitonin has antitumor activity, binds to cholesterol molecules to increase the permeability of cell membranes, and is active in the cleavage of cell membranes in a wide range of cells.

PD-1 PD-L1-IN-52 (Compound Ⅲ-5) is an orally active inhibitor of PD-1 PD-L1 interaction, exhibiting an IC50 of 109.9 nM. It demonstrates antitumor activity in a C57BL 6 mouse model of MC38 colon carcinoma cells expressing human PD-1, achieving a tumor growth inhibition (TGI) rate of 49.6%.

AZ 14145845, a potent and highly selective dual Mer Axl kinase inhibitor (pIC50 = 7 nM and 7.8 nM in pAxl and pMer, respectively), demonstrates significant efficacy in reducing tumor growth in a dose-dependent manner within the Mer and Axl kinase Ba F3 tumor xenograft model in vivo. When combined with anti-PD1 antibodies and ionizing radiation, this compound enhances survival rates in mice bearing MC38-derived tumors. Additionally, AZ 14145845 is orally bioavailable.

Autophagyinducer 6 (Compound 3) inhibits the production of ROS and RNS by targeting COX-1 (IC50=15.3 µM) and COX-2 (IC50=4.58 µM). It facilitates the formation of autophagosomes and induces autophagy (autopagy) as a cellular protection mechanism. Additionally, Autophagyinducer 6 triggers mild apoptosis (apoptosis) and suppresses the proliferation of cancer cell lines MC38, HCT116, and HCT29 with IC50 values of 9.5, 11.5, and 17.6 µM, respectively.

HDAC-IN-53 is an orally active, selective inhibitor of HDAC1-3, with IC50 values of 47 nM, 125 nM, and 450 nM, respectively. It exhibits no inhibitory effects on class II HDACs (HDAC4, 5, 6, 7, 9; IC50 >10 μM). The compound induces caspase-dependent apoptosis and significantly hampers the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice with MC38 colon cancer [1].

Nidanilimab (CAN04) is a fully humanized IL1RAP monoclonal antibody with a Kd value of 1.10 pM. It exhibits antitumor activity by disrupting the IL1α and IL1β signaling pathways and inducing the immune system to destroy tumor cells. Nidanilimab can be used to study solid cancers, such as non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC).

PD-1 PD-L1-IN-32 (compound A56) is a potent inhibitor of PD-1 PD-L1 with an IC50 value of 2.4 nM, demonstrating significant anticancer activity. It effectively suppresses tumor growth in the hPD-L1 MC38 humanized mouse model and exhibits negligible toxicity to the normal functions of the mice [1].

LYP-IN-4 (compound D14), a reversible and selective lymphotyrosine phosphatase (LYP) inhibitor (Ki=1.34 μM, IC50=3.52μM), regulates TCR signaling, increases PD-1 PD-L1 expression, and strengthens anti-tumor immunity. It also stimulates T cell activation, impedes M2 macrophage polarization, and suppresses tumor progression in MC38 isogenic mouse models.

(R)-IDO/TDO-IN-1 (compound 25), an indoleamine-2,3-dioxygenase (IDO) inhibitor, demonstrates good pharmacokinetic properties and exerts anti-tumor effects in the MC38 xenograft model. This compound exhibits synergy when combined with the anti-PD-1 monoclonal antibody (SHR-1210) [1].

TREM2-IN-1 (OPA) is a platinum-based TREM2 inhibitor with anti-cancer activity, blocking DNA replication and inhibiting TREM2 on myeloid cells. It suppresses immune regulatory activity, reducing CD206 and CX3CR1 in a mouse model of colorectal cancer.

BPR5K230 is a dual inhibitor of the receptor tyrosine kinases MER and AXL, exhibiting IC50 values of 4.1 nM and 9.2 nM, respectively. It inhibits the proliferation of Ba F3-MER cells with an IC50 of 5 nM. BPR5K230 demonstrates favorable pharmacokinetics in mice and displays anti-inflammatory and antitumor effects in mouse models against 4T1, MDA-MB-231, MC38, and Hepa1-6.

HPK1-IN-7 is an orally active HPK1 inhibitor. It shows selectivity against IRAK4 (59 nM) and GLK (140 nM).