myeloid-derived

SX-682 is an orally available allosteric inhibitor of CXCR1 and CXCR2 that blocks tumor myeloid suppressor cell recruitment and enhances T cell activation and anti-tumor immunity, with the potential to treat castration-resistant prostate cancer.

TLR7 agonist 29 (Compound 1) is an activator of TLR7, displaying an EC50 of 5.2 nM for human TLR7 and 48.2 nM for mouse TLR7. It can activate bone marrow-derived macrophages (BMDM) and stimulate myeloid cells within the tumor microenvironment, enhancing the expression of PD-L1, CD86, and IFN-α. Additionally, TLR7 agonist 29 can serve as a payload for synthesizing ADCs.

HEMTACWEE1degrader-1 is a WEE1-targeting heterobifunctional chimeric degrader (HEMTAC) facilitated by HSP90, exhibiting an HSP90 enzyme inhibitory activity with an IC50 of 16.76 nM. It enhances the ubiquitination and subsequent degradation of WEE1, effectively blocking the G2/M cell cycle transition. This compound shows anticancer properties in patient-derived xenograft (PDX) models of acute myeloid leukemia (AML). HEMTACWEE1degrader-1 is utilized in AML research.

PAD4-IN-4 (compound 28) is a potent PAD4 inhibitor with an IC50 of 0.79±0.09 μM. It reshapes the neutrophil phenotype, increases the proportion of dendritic cells and M1 macrophages, reduces the number of myeloid-derived suppressor cells, and enhances the tumor immune microenvironment. PAD4-IN-4 is applicable for research in triple-negative breast cancer.

Quizartinib, also know as AC220 and AC010220, is an orally available FLT3 STK1 inhibitor with potential antineoplastic activity. Class III receptor tyrosine kinase inhibitor AC220 selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3 STK1), colony-stimulating factor 1 receptor (CSF1R FMS), stem cell factor receptor (SCFR KIT), and platelet derived growth factor receptors (PDGFRs), resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. Mutations in FLT3, resulting in constitutive activation, are the most frequent genetic alterations in acute myeloid leukemia (AML) and occur in approximately one-third of AML cases.

EVT801 is a highly selective and low-toxic VEGFR-3 inhibitor that inhibits VEGF-C-induced tumor lymphoid and angiogenesis and reduces important circulating immunosuppressive factors (CCL4, CCL5) and myeloid-derived suppressor cells (MDSC).

Flotetuzumab (MGD006; S80880), an investigational CD123/CD3 bispecific dual-affinity retargeting antibody (DART) molecule, reactivates T cells through concurrent engagement with CD123 on target cells and CD3 on effector T cells, facilitating T-cell-mediated cytotoxicity in target cells. Demonstrating an inhibitory effect in a mouse model of patient-derived xenograft (PDX) for acute myeloid leukemia (AML) [1] [2], Flotetuzumab offers potential therapeutic prospects for AML treatment.

LQVTDSGLYRCVIYHPP (LP17) is a peptide and TREM-1 (Triggering Receptor Expressed on Myeloid cells 1) inhibitor derived from a highly conserved sequence between the extracellular structural domains of mouse and human TREM-1 and TLT-1.LP17 inhibits TREM-1 activation through a decoy receptor LP17 inhibits TREM-1 activation by actin through a decoy receptor mechanism, which has the advantage of penetrating the brain barrier and attenuating neuronal damage and inflammatory responses.

Gemtuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of a CD33-specific monoclonal antibody linked to a cytotoxic agent derived from Calicheamicin, utilized in the investigation of acute myeloid leukemia [1].

TAT-CIRP, a trans-activating (Tat) cold-inducible RNA-binding protein-derived peptide, functions as an inhibitor of myeloid differentiation protein 2 (MD2). It has demonstrated significant neuroprotective effects against ischemic and hemorrhagic stroke in mouse models [1].

PMAP-23 is an antimicrobial peptide (AMP) with biological activity, derived from porcine myeloid cells.

Bovine Myeloid Antimicrobial Peptide (BMAP) 28, a synthetic peptide derived from bovine cathelicidin-5 (amino acids 132-158), exhibits antimicrobial activity against E. coli, S. aureus, MRSA, S. epidermidis, and the fungus C. albicans, with minimum inhibitory concentrations (MICs) of 2, 2, 4, 1, and 8 µM respectively. At a concentration of 200 nM, BMAP 28 permeabilizes the inner membrane of E. coli, and at 5 µM, it inhibits herpes simplex virus 1 (HSV-1) replication in Vero 76 cells. Furthermore, at 30 µM, it causes hemolysis in human erythrocytes and cytotoxicity in human neutrophils. In vivo, a dose of 0.8 mg/kg enhances survival in mice infected with E. coli or MRSA, but not P. aeruginosa.

Prostaglandin D2 (PGD2) is a primary enzymatic prostaglandin derived from PGH2 and is abundantly produced in the cerebrospinal fluid (CSF) by the lipocalin-type PGD synthase, and peripherally by myeloid cells such as mast cells and basophils via a hematopoietic-type PGD synthase. PGD2 is chemically unstable and presents challenges for use and analysis due to its brief in vivo half-life. Δ12-PGD2, an initial decomposition product of PGD2, acts as an intermediate in the pathway to Δ12-PGJ2, a cyclopentenone prostaglandin known for its antimitotic and carcinogenic properties. The metabolism of Δ12-PGD2 involves the addition of thiol nucleophiles, a common pathway for many cyclopentenone prostaglandins.

Prostaglandin D2 (PGD2) is one of the five principal prostaglandins enzymatically derived from PGH2. It is abundantly generated in the cerebrospinal fluid (CSF) by lipocalin-type PGD synthase and in peripheral regions by myeloid cells, such as mast cells and basophils, via leukocyte-type PGD synthase. The compound 1,25-trans-PGD2 is an isomer of PGD2, characterized by the alteration of the double bond between carbons 5 and 6 from cis(Z) to trans(E). This trans isomer, found as a 2-5% impurity in most commercial PGD2 bulk drug preparations, is primarily synthesized as an analytical standard to identify and quantify this impurity. Based on existing studies of trans isomers of F-type prostaglandins, 5-trans-PGD2 likely exhibits biological activity comparable to its cis isomer, although no specific published reports confirm this for 5-trans-PGD2.

OPBP-1 is a D-peptide developed through phage display screening, molecular docking, and molecular dynamics simulations. It exhibits high stability, strong antitumor activity, and oral bioavailability. OPBP-1 selectively binds to the PD-L1 protein, significantly blocking the interaction between PD-1 and PD-L1, which helps restore and enhance T lymphocyte function while reducing the proportion of myeloid-derived suppressor cells (MDSCs), counteracting tumor-induced immune evasion. OPBP-1 is applicable for research in cancer immunotherapy.