hematopoietic stem cell

Plerixafor octahydrochloride (JM3100 octahydrochloride) blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell (HSC) release from bone marrow and HSC movement into the peripheral circulation. Plerixafor is a bicyclam with hematopoietic stem cell-mobilizing activity.

Burixafor (also known as TG-0054) is an orally available inhibitor of the CXC chemokine receptor 4 (CXCR4) with receptor binding and hematopoietic stem cell mobilization activities. By binding to the CXCR4 chemokine receptor, Burixafor blocks the binding and subsequent activation of stromal cell-derived factor-1 (SDF-1 or CXCL12) with the CXCR4 receptor, potentially facilitating the mobilization of hematopoietic stem and progenitor cells from the bone marrow into the bloodstream. Note: Elemental analysis shows that this compound is a salt containing 3 HBr and 3 water molecules.

CRX 527 is a TLR4 ligand and serves as an adjuvant for peptide cancer vaccines, enhancing anti-tumor immune responses. CRX 527 also induces hematopoietic stem cell (HSC) differentiation, increasing the proportion and number of LSK cells, and promotes their differentiation into macrophages. This activation bolsters immune defense and protects intestinal epithelium from radiation damage.

XIE18-6 is a novel INK4C inhibitor that selectively blocks the biological activity of the p18 protein, a regulator of the cell cycle. XIE18-6 promotes the ex vivo expansion of both human and murine hematopoietic stem cells, making it a valuable tool for stem cell biology and regenerative medicine research.

BODIPY-aminoacetaldehyde diethyl acetal (BAAA-DA) is a stable precursor to BODIPY-aminoacetaldehyde, a cell-permeable fluorescent substrate for aldehyde dehydrogenase (ALDH).1,2BODIPY-aminoacetaldehyde diethyl acetal is converted under acidic conditions to BODIPY-aminoacetaldehyde (BAAA).2BAAA is cell-permeant and is converted intracellularly by ALDH to BODIPY aminoacetate (BAA), which is retained by cells and can be used to identify cells with high ALDH activity.1BAA is a substrate for the efflux pump P-glycoprotein (P-gp) but co-application of BAAA with a P-gp inhibitor, such as verapamil , inhibits BAA efflux.2BAAA-DA has been used to isolate human hematopoietic progenitor cells, which have high ALDH activity, andviaflow cytometry to sort cancer stem cells that contain high levels of ALDH.1,3BAA used in cells can be excited at 488 nm and displays an emission maximum of 512 nm.4 1.Storms, R.W., Trujillo, A.P., Springer, J.B., et al.Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activityProceedings of the National Academy of Sciences of the United States of America96(16)9118-9123(1999) 2.Smith, C.A., Colvin, M., Storms, R.W., et al.BODIPY aminoacetaldehyde diethyl acetal08010501.81-15(2010) 3.Leng, Z., Yang, Z., Li, L., et al.A reliable method for the sorting and identification of ALDHhigh cancer stem cells by flow cytometryExp. Ther. Med.(2017) 4.Pomper, M.G., Wang, H., Minn, I., et al.Red fluorescent aldehyde dehydrogenase (ALDH) substrate(2015)

NSC23005 sodium is a p18INK inhibitor with potently promoted hematopoietic stem cell (HSC) expansion (ED50: 5.21 nM).

HF51116 is a potent antagonist of CXCR4 that significantly inhibits SDF-1α-induced cell migration, calcium mobilization, and CXCR4 internalization. It also prevents HIV-1 infection utilizing CXCR4. HF51116 has shown investigational potential for HIV-1 infection, hematopoietic stem cell mobilization, and cancer metastasis.

N-Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) acetate, a specific substrate for the N-terminal active site of angiotensin-converting enzyme (ACE), functions as a natural inhibitor of pluripotent hematopoietic stem cell proliferation and exhibits anti-inflammatory and antifibrotic properties [1] [2].

Narsoplimab (OMS 721) is a selective whole-human immunoglobulin gamma-4 (IgG4) monoclonal antibody and a mannan-binding lectin-associated serine protease-2 (MASP-2) inhibitor that binds MASP-2 to prevent lectin pathway activation and inhibit the agglutinin pathway. It is used to study diseases associated with hematopoietic stem cell transplantation in adults.

Briquilimab (JSP-191) is a humanized, aglycosylated monoclonal antibody that directly inhibits the interaction between the stem cell factor (SCF) ligand and its receptor, KIT (CD117), leading to the blockade of the downstream KIT signaling pathway and ultimately inducing mast cell apoptosis; the SCF-KIT interaction is well-characterized as essential for mast cell survival, and its inhibition has been demonstrated to directly trigger mast cell apoptosis primarily through the Bim-mediated pathway, thereby removing the underlying cellular source of inflammation for many immunological and inflammatory diseases, including chronic urticaria and asthma.

EPI-X4, an endogenous peptide fragment of human serum albumin (amino acids 408-423), serves as an antagonist to the chemokine (C-X-C motif) receptor 4 (CXCR4). It effectively prevents calcium mobilization and receptor internalization triggered by chemokine (C-X-C motif) ligand 12 (CXCL12) in HEK293 cells with CXCR4 expression, at concentrations between 0.8 and 1,000 µM. Moreover, EPI-X4 hampers the CXCL12-driven migration of both Jurkat T cells and human CD34+ hematopoietic stem cells. In an acute allergic airway hypereosinophilia mouse model, EPI-X4 intrinsically decreases Cxcr4-dependent inflammatory cell infiltration in airways at a dose of 16 µmol/kg. Additionally, increased urinary EPI-X4 levels, inversely related to glomerular filtration rate (GFR), are observed in chronic kidney disease patients, indicating its potential biomarker role.

MEISi-2 is a specific MEISi inhibitor that inhibits the meis luciferase reporter gene in vitro and induces MEIS-dependent hematopoietic stem cell maintenance and self-renewal, which can be used in research areas such as cardiac injury, hematopoietic problems, bone marrow transplantation and cancer.

Balixafortide (POL6326) is a potent, selective, and well-tolerated peptidic CXCR4 antagonist with an IC50 < 10 nM, and also acts as a potent hematopoietic stem and progenitor cell (HSPC) mobilizing agent. It demonstrates anti-cancer effects[1][2], blocks β-arrestin recruitment and calcium flux with IC50s < 10 nM, and is 1000-fold more selective for CXCR4 than a large panel of receptors, including CXCR7.