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MedKoo Cat#: 555306 | Name: LIT-927
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

LIT-927 is a Locally and Orally Active CXCL12 Neutraligand with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia. displays a higher solubility. LIT-927 reduces eosinophil recruitment in a murine model of allergic airway hypereosinophilia. Combined with a high binding selectivity for CXCL12 over other chemokines, LIT-927 represents a powerful pharmacological tool to investigate CXCL12 physiology in vivo, and to explore the activity of chemokine neutralization in inflammatory and related diseases.

Chemical Structure

LIT-927
CAS#2172879-52-4

Theoretical Analysis

MedKoo Cat#: 555306

Name: LIT-927

CAS#: 2172879-52-4

Chemical Formula: C17H13ClN2O3

Exact Mass: 328.0615

Molecular Weight: 328.75

Elemental Analysis: C, 62.11; H, 3.99; Cl, 10.78; N, 8.52; O, 14.60

Price and Availability

Size Price Availability Quantity
10mg USD 110.00 Ready to ship
25mg USD 190.00 Ready to ship
50mg USD 350.00 Ready to ship
100mg USD 550.00 Ready to ship
200mg USD 950.00 Ready to ship
500mg USD 1,950.00 Ready to ship
1g USD 3,450.00 Ready to ship
2g USD 5,950.00 Ready to ship
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Related CAS #
No Data
Synonym
LIT-927; LIT 927; LIT927;
IUPAC/Chemical Name
4-(4-Chlorophenyl)-6-(4-hydroxy-3-methoxyphenyl)pyrimidin-2(1H)-one
InChi Key
BYYRNPIGDRRGLJ-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H13ClN2O3/c1-23-16-8-11(4-7-15(16)21)14-9-13(19-17(22)20-14)10-2-5-12(18)6-3-10/h2-9,21H,1H3,(H,19,20,22)
SMILES Code
O=C1N=C(C2=CC=C(Cl)C=C2)C=C(C3=CC=C(O)C(OC)=C3)N1
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
LIT-927 is a novel neutraligand of CXCL12 with Ki value of 267 nM for inhibition of Texas red-labeled CXCL12 (CXCL12-TR) binding.
In vitro activity:
The selectivity of 57 was evaluated toward four other chemokines, namely, CCL17, CCL22, CCL5, and CCL2, by using the neutraligand protocol of the recently reported time-resolved intracellular calcium recording (TRIC-r) assay(39) (Figure 7). This generic assay enables the discovery of chemokine-neutralizing molecules (neutraligands) by differentiating them from molecules that block the receptor (antagonists). Initially described for the identification of CCL17 and CCL22 neutraligands, the assay has been setup for CXCL12. Thereby, as depicted in Figure 7, pyrimidinone 57 at 10 μM is able to inhibit the increase in intracellular calcium concentration in EGFP-CXCR4+ HEK cells in response to CXCL12, while it has no effect on calcium responses triggered by either CCL17 or CCL22 on EGFP-CCR4+ HEK cells, CCL5 on EGFP-CCR5+ HEK cells, or CCL2 on EGFP-CCR2+ HEK cells. These results demonstrate the high selectivity of 57 toward CXCL12 vs other chemokines also involved in asthma. Reference: J Med Chem. 2018 Sep 13;61(17):7671-7686. https://doi.org/10.1021/acs.jmedchem.8b00657
In vivo activity:
Male Wistar rats were injected with monocrotaline (MCT) or were subjected to SU5416 followed by 3-week hypoxia to induce severe PH. After PH establishment, assessed by pulsed-wave Doppler echocardiography, MCT-injected or SU5416 plus chronic hypoxia (SuHx) rats were randomized to receive CXCL12 neutraligands chalcone 4 or LIT-927 (100 mg/kg/day), the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100 (5 mg/kg/day), or vehicle, for 2 or 3 weeks, respectively. At the end of these treatment periods, echocardiographic and haemodynamic measurements were performed and tissue samples were collected for protein expression and histological analysis. Daily treatment of MCT-injected or SuHx rats with established PH with chalcone 4 or LIT-927 partially reversed established PH, reducing total pulmonary vascular resistance, and remodelling of pulmonary arterioles. Consistent with these observations, we found that neutralization of CXCL12 attenuates right ventricular hypertrophy, pulmonary vascular remodelling, and decreases pulmonary artery smooth muscle cell (PA-SMC) proliferation in lungs of MCT-injected rats and SuHx rats. Importantly, CXCL12 neutralization with either chalcone 4 or LIT-927 inhibited the migration of PA-SMCs and pericytes in vitro with a better efficacy than AMD3100. Finally, we found that CXCL12 neutralization decreases vascular pericyte coverage and macrophage infiltration in lungs of both MCT-injected and SuHx rats. Reference: Cardiovasc Res. 2020 Mar 1;116(3):686-697. https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvz153
Solvent mg/mL mM comments
Solubility
DMSO 66.0 200.76
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 328.75 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
1. Regenass P, Abboud D, Daubeuf F, Lehalle C, Gizzi P, Riché S, Hachet-Haas M, Rohmer F, Gasparik V, Boeglin D, Haiech J, Knehans T, Rognan D, Heissler D, Marsol C, Villa P, Galzi JL, Hibert M, Frossard N, Bonnet D. Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia. J Med Chem. 2018 Sep 13;61(17):7671-7686. doi: 10.1021/acs.jmedchem.8b00657. Epub 2018 Aug 28. PMID: 30106292.
In vivo protocol:
1. Bordenave J, Thuillet R, Tu L, Phan C, Cumont A, Marsol C, Huertas A, Savale L, Hibert M, Galzi JL, Bonnet D, Humbert M, Frossard N, Guignabert C. Neutralization of CXCL12 attenuates established pulmonary hypertension in rats. Cardiovasc Res. 2020 Mar 1;116(3):686-697. doi: 10.1093/cvr/cvz153. PMID: 31173066. 2. Regenass P, Abboud D, Daubeuf F, Lehalle C, Gizzi P, Riché S, Hachet-Haas M, Rohmer F, Gasparik V, Boeglin D, Haiech J, Knehans T, Rognan D, Heissler D, Marsol C, Villa P, Galzi JL, Hibert M, Frossard N, Bonnet D. Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia. J Med Chem. 2018 Sep 13;61(17):7671-7686. doi: 10.1021/acs.jmedchem.8b00657. Epub 2018 Aug 28. PMID: 30106292.
1: Regenass P, Abboud D, Daubeuf F, Lehalle C, Gizzi P, Riché S, Hachet-Haas M, Rohmer F, Gasparik V, Boeglin D, Haiech J, Knehans T, Rognan D, Heissler D, Marsol C, Villa P, Galzi JL, Hibert M, Frossard N, Bonnet D. Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia. J Med Chem. 2018 Aug 14. doi: 10.1021/acs.jmedchem.8b00657. [Epub ahead of print] PubMed PMID: 30106292.