| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
ATX/autotaxin
CRT0273750 targets autotaxin (ATX), an enzyme that produces lysophosphatidic acid (LPA) from lysophosphatidylcholine. It acts as an ATX inhibitor, reducing plasma LPA levels. It also targets the Wnt/β-catenin signaling pathway. |
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| ln Vitro |
The IC50 of CRT0273750 evaluated in biochemical studies and choline release assay experiments were 0.01 μM and 0.014 μM, respectively [1]. CRT0273750 curve inhibits the migration of 4T1 cells with an EC50 of 0.025 μM[1].
CRT0273750 modulates LPA levels in plasma. It is a lead compound of ATX inhibitors. It has activity against the Wnt/β-catenin signaling pathway. It is used in ATX/LPA-dependent cancer models. |
| ln Vivo |
The moderate blood clearance of CRT0273750 (1 mg/kg; intravenous) is 41 mL/min/kg[1]. Cmax, AUC, and t1/2 values for CRT0273750 (10 mg/kg; face) were 3.8, 3.9, and 3.8, respectively.
CRT0273750 modulates LPA levels in plasma in vivo. It can be used in ATX/LPA-dependent cancer models. It is suitable for in vivo studies. |
| Enzyme Assay |
CRT0273750 is evaluated in cell-free enzymatic assays using purified autotaxin. The compound is incubated with ATX and a substrate, and the inhibition of enzyme activity is measured. IC50 values are determined to quantify the potency of ATX inhibition. LPA production is measured using biochemical assays.
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| Cell Assay |
CRT0273750 is assessed in cell-based assays using cancer cell lines. Cells are treated with CRT0273750, and LPA levels and Wnt/β-catenin signaling are measured. The compound's effects on cell proliferation and survival are evaluated.
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| Animal Protocol |
Animal/Disease Models: Balb-c nu/nu (nude) mice [1]
Doses: 10, 30 and 100 mg/kg Route of Administration: Oral (pharmacokinetic/PK/PK analysis) Experimental Results: Cmax were 3.8, 10.9 and 18.1 µM respectively. AUCs were 3.2, 15.2 and 59.3 µM.h respectively. t1/2s are 1.4, 0.9 and 1.3 hrs (hrs (hours)) respectively. CRT0273750 is administered in animal models to evaluate its effects on ATX/LPA signaling and tumor growth. It modulates LPA levels in plasma. It can be used in ATX/LPA-dependent cancer models. Efficacy is assessed by measuring tumor growth and LPA levels. |
| ADME/Pharmacokinetics |
CRT0273750 has a molecular weight of 502.92 and a molecular formula of C25H22ClF3N4O2. It has a CAS number of 1979939-16-6. The compound is soluble in DMSO at ≥200 mg/mL. It should be stored as a powder at -20°C for up to 3 years.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is available for CRT0273750. The compound is for research use only and is not intended for human therapeutic use. It is a lead compound of ATX inhibitors.
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| References | |
| Additional Infomation |
IOA-289, an autosecodylin inhibitor, is a small molecule autosecodylin (ATX; exonucleotide pyrophosphatase/phosphodiesterase family member 2; ENPP2) inhibitor with high oral bioavailability and potential antifibrotic and antitumor activity. After oral administration, IOA-289 targets and binds to the substrate-binding pocket and lysophosphatidylcholine (LPA) carrier channel of ATX, thereby inhibiting ATX activity. This directly inhibits tumor cell proliferation, reduces fibrosis in the tumor microenvironment (TME), allows lymphocytes to infiltrate the tumor, and enhances the immune response against tumor cells. ATX is a secreted glycoprotein with lysophosphatidylcholine D activity, which hydrolyzes lysophosphatidylcholine (LPC) to LPA. LPA-mediated signaling pathways play a crucial role in cell migration, proliferation, and survival during fibrosis. ATX and LPA are overexpressed in various tumors.
CRT0273750 is an ATX inhibitor. It is also known as IOA-289. It modulates plasma LPA levels. It is used in ATX/LPA-dependent cancer models. It is not approved for clinical use. |
| Molecular Formula |
C25H22CLF3N4O2
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|---|---|
| Molecular Weight |
502.915995121002
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| Exact Mass |
502.138
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| Elemental Analysis |
C, 59.71; H, 4.41; Cl, 7.05; F, 11.33; N, 11.14; O, 6.36
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| CAS # |
1979939-16-6
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| PubChem CID |
122199235
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| Appearance |
White to off-white solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
684
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@H](C1=CC=C(C=C1)Cl)NC(=O)CCC2=NC3=C(N2CC4=CC=C(C=C4)OC(F)(F)F)N=CC=C3
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| InChi Key |
HXYXHSDYBDFOFO-INIZCTEOSA-N
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| InChi Code |
InChI=1S/C25H22ClF3N4O2/c1-16(18-6-8-19(26)9-7-18)31-23(34)13-12-22-32-21-3-2-14-30-24(21)33(22)15-17-4-10-20(11-5-17)35-25(27,28)29/h2-11,14,16H,12-13,15H2,1H3,(H,31,34)/t16-/m0/s1
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| Chemical Name |
N-[(1S)-1-(4-chlorophenyl)ethyl]-3-[3-[[4-(trifluoromethoxy)phenyl]methyl]imidazo[4,5-b]pyridin-2-yl]propanamide
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| Synonyms |
CRT-0273750; CRT 0273750; CRT0273750; 1979939-16-6; CHEMBL3917975; (S)-N-(1-(4-Chlorophenyl)ethyl)-3-(3-(4-(trifluoromethoxy)benzyl)-3H-imidazo[4,5-b]pyridin-2-yl)propanamide; N-[(1S)-1-(4-chlorophenyl)ethyl]-3-[3-[[4-(trifluoromethoxy)phenyl]methyl]imidazo[4,5-b]pyridin-2-yl]propanamide; N-[1(S)-(4-Chlorophenyl)-ethyl]-3-[3-(4-trifluoromethoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl]-propionamide; LYY3P2KA27; SCHEMBL17966918; CRT0273750
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~497.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9884 mL | 9.9419 mL | 19.8839 mL | |
| 5 mM | 0.3977 mL | 1.9884 mL | 3.9768 mL | |
| 10 mM | 0.1988 mL | 0.9942 mL | 1.9884 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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