stromal

Etonogestrel (Implanon) is a steroidal progestin used as hormonal contraceptives.

N-Oleoyl-L-Serine (N-Oleoylserine) is an endogenous long-chain fatty acid amide that is a lipid modulator of bone remodeling and stimulates osteoclast apoptosis which can be used to study osteoporosis. N-Oleoyl-L-Serine showed high activity in an osteoblast proliferation assay.N-Oleoyl-L-Serine promotes osteoclast apoptosis by inhibiting Erk1 2 phosphorylation and expression of nuclear κB ligand (RANKL) receptor activator in bone marrow stromal cells and osteoblasts, which attenuates osteoclast populations.

Plerixafor (AMD-3329), a chemokine receptor antagonist, blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4.

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.

Regorafenib Hydrochloride (BAY73-4506 hydrochloride) is a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity

ML-9 suppresses MLCK, PKA, and PKC activity with Ki values of 4, 32, and 54 μM, respectively. ML-9 is a selective and effective inhibitor of Akt kinase, inhibits myosin light-chain kinase (MLCK), and stromal interaction molecule 1 (STIM1) activity. ML-9 causes autophagy by stimulating autophagosome formation and inhibiting their degradation.

Halofuginone specifically inhibits collagen type I gene expression and matrix metalloproteinase 2 (MMP-2) gene expression, which may result in the suppression of angiogenesis, tumor stromal cell development, and tumor cell growth. Halofuginone Hydrobromide is the hydrobromide salt of halofuginone, a semisynthetic quinazolinone alkaloid anticoccidial derived from the plant Dichroa febrifuga, with antifibrotic and potential antineoplastic activities. These effects appear to be due to halofuginone-mediated inhibition of the collagen type I and MMP-2 promoters. Collagen type I and MMP-2 play important roles in fibroproliferative diseases.

Hydroxysafflor yellow A (Safflomin A) inhibits adipogenesis by increasing HSL promoter activities, effectively protects the liver from long-term alcohol injury by enhancing antioxidant capacity and inhibiting the expression of TGF-β, prevents steroid-induced avascular necrosis of the femoral head by inhibiting primary bone marrow-derived mesenchymal stromal cells, and exhibits anti-tumor effects.

ML-9 (free base) suppresses MLCK, PKA, and PKC activity (Ki: 4, 32, and 54 μM, respectively). ML-9 (free base) is a selective and effective inhibitor of Akt kinase, inhibits myosin light-chain kinase (MLCK), and stromal interaction molecule 1 (STIM1) acti

Pyr10 is a pyrazole derivative and a selective TRP cation 3 inhibitor that distinguishes between receptor-operated TRPC3 and native stromal interaction molecule 1 (STIM1)/Orai1 channels. Pyr10 inhibits Ca2+ influx in carbachol-stimulated TRPC3-transfected HEK293 cells (IC50: 0.72 μM) and has an IC50 of 13.08 μM for store-operated Ca2+ entry in BRL-2H3 cells.

USL311 is a CXCR4 receptor antagonist which prevents the binding of stromal-cell derived factor-1 (SDF-1 or CXCL12) to CXCR4. USL311 inhibits CXCR4 activation and decreases proliferation and migration of CXCR4-expressing tumor cells, with anti-tumor activ

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.

KIT PDGFRA-IN-1 (compound 19) is an inhibitor targeting the stem cell growth factor receptor (KIT) and platelet-derived growth factor receptor alpha (PDGFRA). Its IC50 values are 2.3 µM for KIT-wt, 12 µM for KIT-D816H, 492 µM for KIT-T670I, 0.8 µM for PDGFRA-wt, 99.9 µM for PDGFRA-D842V, 42.3 µM for PDGFRA-T674I, and 4.3 µM for PDGFRA-G680R. The GR50 values for GIST-T1, T1-a-D842V, and GIST-48B cell lines (gastrointestinal stromal tumor cell lines with PDGFR and KIT mutations) are 12 nM, 8900 nM, and ≥10,000 nM, respectively.

PDGFRαkinase inhibitor 3 (Compound L7) is a potent inhibitor targeting the PDGFRαD842V kinase, exhibiting IC50 values of 23.8 nM in biochemical assays and 2.1 nM in cellular assays. It binds to the ATP binding site of PDGFRαD842V, blocking downstream signaling pathways and inhibiting kinase activity. PDGFRαkinase inhibitor 3 is applicable in gastrointestinal stromal tumor (GIST) research.

Imatinib is a multi-target inhibitor of v-Abl, c-Kit, and PDGFR (IC50: 0.6 μM, 0.1 μM, and 0.1 μM, respectively). Imatinib is used to treat chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs), and a number of other malignancies.

Glycitin (Glycitein 7-O-β-glucoside), a natural isoflavone isolated from legumes, promotes the proliferation of bone marrow stromal cells and osteoblasts while suppressing bone turnover.

Lipid-derived lipoxins are produced at the site of vascular and mucosal inflammation where they down-regulate polymorphonuclear leukocyte recruitment and function. 15(R)-Lipoxin A4 (15(R)-LXA4) is derived from the aspirin-triggered formation of 15(R)-HETE from arachidonic acid. [1] [2] 15(R)-LXA4 inhibits LTB4-induced chemotaxis, adherence, and transmigration of neutrophils with twice the potency of LXA4 demonstrating activity in the nM range.[2] [3] The anti-inflammatory effects of aspirin may be ascribed in part to the ability of 15(R)-LXA4 to regulate leukocyte function.[4] 15(R)-LXA4 is reported to promote resolution of inflammation in LPS-treated stromal cells derived from intermediate-stage diseased supraspinatus tendons as evidenced by increased expression of the STAT-6 pathway target genes, ALOX15 and CD206.[5]

KLD-12, a 12-residue self-assembling peptide, displays properties that promote chondrogenic differentiation of bone marrow stromal cells (BMSCs). Moreover, KLD-12 hydrogel can effectively fill full-thickness osteochondral defects in their original location, leading to improved cartilage repair.

NT157 is a small molecule tyrphostin targeting IRS protein and has the potential to inhibit IGF-1R and STAT3 signaling pathways in TME cancer cells and stromal cells, resulting in decreased cancer cell survival.

AZD3229 is a potent pan-KIT mutant inhibitor for the treatment of gastrointestinal stromal tumors. It demonstrates potent single-digit nM growth inhibition across a broad cell panel.

Tigogenin is one of steroidal sapogenins which is widely used for synthesizing steroid drugs. It might have protective effect on bone and be helpful in preventing the development of osteoporosis.

INCB16562 is a novel, selective, and orally bioavailable small-molecule inhibitor of JAK1 and JAK2 markedly selective over JAK3. Treatment of myeloma cells with INCB16562 potently inhibited interleukin-6 (IL-6)-induced phosphorylation of STAT3. INCB16562 abrogated the protective effects of recombinant cytokines or bone marrow stromal cells and sensitized myeloma cells to cell death by exposure to dexamethasone, melphalan, or bortezomib. Oral administration of INCB16562 antagonized the growth of myeloma xenografts in mice and enhanced the antitumor activity of relevant agents in combination studies. INCB16562 is a potent JAK1 2 inhibitor and that mitigation of JAK STAT signaling by targeting JAK1 and JAK2 will be beneficial in the treatment of myeloma patients, particularly in combination with other agents. ( source: Neoplasia. 2010 Jan;12(1):28-38. ).

AS1940477 is p38 MAPK inhibitor. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms. In human peripheral blood mononuclear cells, AS1940477 inhibited lipopolysaccharide (LPS)- or phytohemagglutinin A (PHA)-induced production of proinflammatory cytokines, including TNFα, IL-1β, and IL-6 at low concentrations (LPS TNFα, IC(50)=0.45n M; PHA TNFα, IC(50)=0.40 nM). In addition, equivalent concentrations of AS1940477 that inhibited cytokine production also inhibited TNFα- and IL-1 β-induced production of IL-6, PGE(2), and MMP-3 in human synovial stromal cells. AS1940477 was also found to potently inhibit TNF production in whole blood (IC(50)=12 nM) and effectively inhibited TNFα production induced by systemically administered LPS in rats at less than 0.1mg kg (ED(50)=0.053 mg kg) with an anti-inflammatory effect lasting for 20h after oral administration. Overall, this stu......

MS-0022 is a SMO antagonist. MS-0022 showed effective Hh signaling pathway inhibition at the level of SMO in the low nM range, and Hh pathway inhibition downstream of Suppressor of fused (SUFU) in the low µM range. MS-0022 reduced growth in the tumor cell lines PANC-1, SUIT-2, PC-3 and FEMX in vitro. MS-0022 is a treatment led to a transient delay of tumor growth that correlated with a reduction of stromal Gli1 levels in SUIT-2 xenografts in vivo.