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]

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

MC38 SLP Adpgk (Adpgk peptide) is a neoantigen peptide generated from a mutation in the MC38 colon cancer cell line and is applicable for nanoparticle vaccine synthesis.

The peptide neoantigen MC38 SLP Reps1 is derived from the mutated MC38 colon cancer cell line and can be used for the synthesis of nanoparticle vaccines.

MC3817 is a selective DNMT inhibitor, with IC50 values of 0.044 μM for DNMT1 and greater than 10 μM for DNMT3A/3L. It inhibits P53-dependent cancer cell proliferation, induces apoptosis and DNA damage, and elevates the levels of cleaved Caspase 3, P53, and γH2AX. MC3817 is applicable in research on non-small cell lung cancer, colon cancer, cervical cancer, triple-negative breast cancer, and histiocytic lymphoma.

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.

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-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.

ZSA-215 is an orally active STING agonist with an EC50 value of 3.3 μM. In the MC38 colon cancer model, ZSA-215 facilitates tumor regression and supports long-term survival in mice. It is utilized for colon cancer research.

PVTX-405 is a selective oral IKZF2 molecular glue degrader with a DC50 of 0.7 nM and a maximum degradation (Dmax) of 91%. It enhances degradation efficiency, significantly reduces off-target degradation, and minimizes hERG inhibition with an IC50 of 48 µM. PVTX-405 effectively inhibits MC38 tumor growth in Crbn391VC57BL/6 mouse xenograft models and shows superior synergistic anticancer effects when combined with immune checkpoint therapies (ICTs) such as anti-PD1 or anti-LAG3 antibodies.

USP7-IN-18 (Compound X21) serves as a novel USP7 inhibitor by directly suppressing enzyme activity and modulating downstream pathways, including the newly identified PCLAF target. At concentrations of 0.25-1 μM for 24 hours, it exhibits inhibitory effects. USP7-IN-18 effectively reduces proliferation in leukemia (RS4;11) and colon cancer (MC38/CT26.WT) cells at 0.01-100 μM over 72 hours. It demonstrates high selectivity for USP7 at 2.5 μM within 0.5 hours, surpassing eight other deubiquitinating enzymes. SPR analysis shows that at 1.95-2000 nM for 3 minutes, the compound binds the catalytic domain of USP7 with a KD value of 4.9 μM.

Adenosine receptor antagonist 6 is an orally active, selective (S)-enantiomer compound that acts as an A2A adenosine receptor (A2AAR) antagonist. It binds to the A2A adenosine receptor with a Ki value of 19.18 nM. This antagonist inhibits cAMP production mediated by 5’-N-ethylcarboxamide adenosine (NECA) with an IC50 value of 0.089 μM and reduces immunosuppression, while enhancing the secretion of IL-2 and IFN-γ. It counteracts adenosine-induced immunosuppression in T cell activation and cytokine release and inhibits tumor growth in CT26/MC38 xenograft models, making it applicable for colorectal cancer research.

PROTACHPK1 Degrader-5 is a potent, orally active HPK1 PROTAC degrader with a DC50 of 5.0 nM and a Dmax of at least 99%. It significantly inhibits HPK1 by degrading it, reducing SLP76 phosphorylation, and enhancing ERK pathway activation, which in turn stimulates the release of IL-2 and IFN-γ. This compound effectively counteracts immune suppression induced by PGE2, NECA, or TGF-β. Alone, PROTACHPK1 Degrader-5 is capable of suppressing tumor growth in MC38 syngeneic mouse models. It is used in research for immunotherapy applications in cancers such as colorectal cancer.

A2AAR antagonist 4 is an orally active antagonist of the A2A adenosine receptor (A2AAR) with a Ki value of 0.36 nM and a KB value of 1 nM in humans. At a concentration of 10 μM, it fully inhibits both human A2AAR and human A2bAR. A2AAR antagonist 4 is applicable in cancer research, such as studies involving MC38 tumors.

RORγ agonist2 (Compound 34) is a selective RORγ agonist with an EC50 of 0.03 μM for hRORγ. It significantly inhibits tumor growth in an MC38 tumor mouse model with the same genetic background.

HPK1-IN-62 is a selective, orally active inhibitor of HPK-1 with an IC50 of 1.22 nM. It significantly enhances selectivity for GLK (> 665-fold) and LCK (> 1095-fold). HPK1-IN-62 boosts T cell activation and shows synergy with anti-mPD-1 therapy in inhibiting tumor growth in the MC38 tumor model. It is applicable for research in colon cancer and cancer immunotherapy.

YCH3292, a derivative of YCH189, is a potent, selective, and orally active PARP1/2 inhibitor with IC50 values of less than 0.001 nM. YCH3292 enhances the stability of PARP-DNA complexes and exhibits strong antiproliferative activity. It induces DNA double-strand breaks, increases protein levels of γH2AX, P-RPA32, and P-Chk1, and causes tumor cells to undergo S phase or G2/M phase arrest and apoptosis (apoptosis). In the MC38 xenograft model, YCH3292 effectively suppresses tumor growth.

TNG260 is a selective and orally effective inhibitor of HDAC1 and the CoREST complex, exhibiting 10-fold selectivity for HDAC1 over HDAC3 and 500-fold selectivity for CoREST over NuRD and Sin3 complexes. TNG260 reshapes the tumor immune microenvironment by reducing immunosuppressive neutrophil infiltration, enhancing effector T-cell recruitment, reversing anti-PD-1 resistance driven by STK11 deficiency, and inducing durable tumor regression in combination with α-PD-1 in STK11-mutant MC38 tumor models while maintaining lower bone marrow toxicity than non-selective HDAC inhibitors.

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].

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].