LIT-927 |
Catalog No.GC19486
One-Click Copy Product Info
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LIT-927 is a highly selective and orally active C-X-C chemokine ligand 12 (CXCL12) neutraligand that effectively inhibits the interaction between the CXCL12 and its receptor CXCR4, with a binding affinity Ki value of 267nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2172879-52-4
Sample solution is provided at 25 µL, 10mM.
LIT-927 is a highly selective and orally active C-X-C chemokine ligand 12 (CXCL12) neutraligand that effectively inhibits the interaction between the CXCL12 and its receptor CXCR4, with a binding affinity Ki value of 267nM[1]. CXCL12 is a key chemokine involved in inflammation, immune cell recruitment, and tissue homeostasis, exerting biological functions through binding to receptors CXCR4/CXCR7[2]. By blocking CXCL12, LIT-927 reduces inflammation and has been used in the treatment and research of allergic airway diseases and autoimmune disorders[3,4].
In vitro, treatment of MRL/lpr mouse splenocytes with LIT-927 (0-20μM) for 24h downregulated the overexpression of activation markers CD25 and CD86 on CD4+ T cells and reduced CD40 expression on B cells in a dose-dependent manner[5]. LIT-927 (10, 30μM) treatment of human pulmonary artery smooth muscle cells (PA-SMCs) for 24h inhibited PA-SMC migration in a concentration-dependent manner[6]. LIT-927 (0.5μM) treatment of human glioblastoma U-87 MG cells for 24h suppressed temozolomide (TMZ)-induced phosphorylation of ERK and NF-κB[7].
In vivo, intranasal administration of LIT-927 (197ng/mL; 10μL) to house dust mite-sensitized C57Bl/6 mice for 2 weeks significantly reduced respiratory symptom scores, effectively inhibited pericyte migration, and alleviated airway smooth muscle thickening[8]. Intraperitoneal injection of LIT-927 (100mg/kg/day) for 2 weeks in monocrotaline (MCT)-induced pulmonary artery hypertensive rats significantly reduced mean pulmonary arterial pressure (mPAP), total pulmonary vascular resistance (TPVR), and right ventricular hypertrophy (Fulton index)[6].
References:
[1] REGENASS P, ABBOUD D, DAUBEUF F, et al. Discovery of a locally and orally active CXCL12 neutraligand (LIT-927) with anti-inflammatory effect in a murine model of allergic airway hypereosinophilia[J]. Journal of Medicinal Chemistry, 2018, 61(17): 7671-7686.
[2] MINAMI H, NAGAHARU K, NAKAMORI Y, et al. CXCL12-CXCR4 axis is required for contact-mediated human B lymphoid and plasmacytoid dendritic cell differentiation but not T lymphoid generation[J]. The Journal of Immunology, 2017, 199(7): 2343-2355.
[3] JANSSENS R, STRUYF S, PROOST P. The unique structural and functional features of CXCL12[J]. Cellular & Molecular Immunology, 2018, 15(4): 299-311.
[4] LU L, LI J, JIANG X, et al. CXCR4/CXCL12 axis: "old" pathway as "novel" target for anti-inflammatory drug discovery[J]. Medicinal Research Reviews, 2024, 44(3): 1189-1220.
[5] SCHALL N, DAUBEUF F, MARSOL C, et al. A selective neutraligand for CXCL12/SDF-1α with beneficial regulatory functions in MRL/Lpr lupus prone mice[J]. Frontiers in Pharmacology, 2021, 12: 752194.
[6] BORDENAVE J, THUILLET R, TU L, et al. Neutralization of CXCL12 attenuates established pulmonary hypertension in rats[J]. Cardiovascular Research, 2020, 116(3): 686-697.
[7] CHIANG I T, LIU Y C, LIU H S, et al. Regorafenib reverses temozolomide-induced CXCL12/CXCR4 signaling and triggers apoptosis mechanism in glioblastoma[J]. Neurotherapeutics, 2022, 19(2): 616-634.
[8] BIGNOLD R, SHAMMOUT B, ROWLEY J E, et al. Chemokine CXCL12 drives pericyte accumulation and airway remodeling in allergic airway disease[J]. Respiratory Research, 2022, 23: 183.
| Cell experiment [1]: | |
Cell lines | MRL/lpr mice spleen cells |
Preparation Method | Unstimulated cells (2 × 106 per well) sorted from the spleen of 11-13 week-old female MRL/lpr mice (2 mice per group; 2 independent experiments) were incubated with increasing concentrations of LIT-927 (0-20µM) at 37℃ for 24h and analyzed by flow cytometry. |
Reaction Conditions | 0, 5, 10, 20μM; 24h |
Applications | In a dose-response manner, LIT-927 down-regulated the overexpression of CD25 and CD86/B7-2 activation markers at the surface of splenic MRL/lpr CD4+ T cells, and CD40 at the surface of MRL/lpr B cells. |
| Animal experiment [2]: | |
Animal models | Wistar rats with MCT-induced (60mg/kg) pulmonary arterial hypertension |
Preparation Method | Young male Wistar rats received a single subcutaneous injection of MCT (60mg/kg). At Day 7, MCT-injected rats were treated for 2 weeks with daily intraperitoneal (i.p.) injections of LIT-927 (100mg/kg/day). |
Dosage form | 100mg/kg/day; 2 weeks; i.p. |
Applications | MCT-injected rats treated with LIT-927 (100mg/kg/day) significantly reduced mPAP and TPVR, and attenuated right ventricular hypertrophy. |
References: | |
| Cas No. | 2172879-52-4 | SDF | |
| Canonical SMILES | ClC1=CC=C(C(C=C(C2=CC=C(O)C(OC)=C2)N3)=NC3=O)C=C1 | ||
| Formula | C₁₇H₁₃ClN₂O₃ | M.Wt | 328.75 |
| Solubility | DMF: 1mg/mL | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0418 mL | 15.2091 mL | 30.4183 mL |
| 5 mM | 608.4 μL | 3.0418 mL | 6.0837 mL |
| 10 mM | 304.2 μL | 1.5209 mL | 3.0418 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 11 reference(s) in Google Scholar.)