| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
p38α MAPK (IC50 = 63.3 nM against human p38α); p38β (14‑fold less potent); selective against a panel of 91 kinases (≥300‑fold selective). [1]
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| ln Vitro |
AL8697 inhibits LPS‑induced PGE2 production in human whole blood with an IC50 of 400 nM (unpublished results). [1]
AL8697 inhibits LPS‑induced TNFα production in human whole blood with an IC50 of 110 nM (unpublished results). [1] The compound shows chondroprotective potential via inhibition of IL‑1β‑induced chondrocyte expression of COX‑2, MMP13 and inducible NOS, as suggested by the literature. [1] |
| ln Vivo |
In both the right and left paw, AL 8697 (1-30 mg/kg; oral; once daily for 10 days) reduces edema in a dose-dependent manner [1].
In the rat adjuvant‑induced arthritis (AIA) model, AL8697 administered orally once daily (qd) at 30 mg·kg⁻¹ inhibited right paw swelling by 52±3% and left paw swelling by 76±3%. At 10 mg·kg⁻¹ qd, it inhibited right paw swelling by 49±2% and left paw swelling by 78±2%. [1] At 10 mg·kg⁻¹ qd, AL8697 improved the radiological score by 76±4% (right paw) and reduced splenomegaly by 74±3%. [1] At the same dose, it reversed thymus atrophy by 46±12% and improved the body weight change index (0.57±0.07). Plasma α2‑macroglobulin was reduced by 95±2% at 10 mg·kg⁻¹ qd. [1] Histological assessment (10 mg·kg⁻¹ qd) showed slight to moderate inflammation of the synovial membrane in the absence of cartilage damage, with an overall histological score improvement. [1] AL8697 treatment caused leukocytosis (increase in neutrophils and monocytes) and increased total plasma cholesterol (mean 39% above normal control rats at 10 mg·kg⁻¹ qd). [1] |
| Enzyme Assay |
p38 MAPK inhibition was measured as described in Lumeras et al. (2009). The IC50 value for human p38α was determined to be 63.3 nM. Selectivity of AL8697 was assessed against a panel of 91 kinases at a single concentration of 10 μM, showing at least 300‑fold selectivity over other kinases. For p38β, the compound was 14‑fold less potent than against p38α. [1]
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| Cell Assay |
Human whole blood was stimulated with lipopolysaccharide (LPS), and the production of prostaglandin E2 (PGE2) was measured. AL8697 inhibited LPS‑induced PGE2 production with an IC50 of 400 nM (unpublished results). [1]
In a separate assay using human whole blood stimulated with LPS, tumor necrosis factor alpha (TNFα) production was measured. AL8697 inhibited LPS‑induced TNFα with an IC50 of 110 nM (unpublished results). [1] |
| Animal Protocol |
Animal/Disease Models: Male Wistar rat[1]
Doses: 1, 3, 10, 30 mg/kg Route of Administration: po (oral gavage); one time/day for 10 days Experimental Results: Dose-dependent reduction of edema in the right and left paws , resulting in greater improvement in the contralateral uninjected paw. Male Wistar rats (150‑175 g) were injected intraplantarly in the left hind paw with 0.1 mL of a 5 mg·mL⁻¹ Mycobacterium tuberculosis suspension in paraffin oil to induce adjuvant arthritis. On day 11 post‑induction, rats with right paw volumes around 2.0 mL were selected and randomly divided into treatment groups (n=6). AL8697 was freshly suspended in sterile 0.5% methylcellulose / 0.1% Tween‑80 solution at a volume of 10 mL·kg⁻¹ body weight. From day 11 to day 20, the compound was administered orally once daily (qd) at doses of 1, 3, 10, or 30 mg·kg⁻¹. Paw volumes were measured by plethysmography every other day until day 21. At study completion, blood samples were collected for haematological and biochemical analysis, and spleen, thymus, and brain were removed and weighed. Hind paws were excised for X‑ray and histological evaluation. [1] |
| ADME/Pharmacokinetics |
In Wistar rats, following oral administration of AL8697 at 10 mg·kg⁻¹, the plasma half‑life (t1/2) was 3.3 hours. [1]
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| Toxicity/Toxicokinetics |
In the rat AIA model, AL8697 treatment induced leukocytosis (significant increase in neutrophils and monocytes) at 10 mg·kg⁻¹ qd. It also caused an increase in total plasma cholesterol levels (mean 39% above normal control rats at 10 mg·kg⁻¹ qd). No hepatotoxicity or elevation of transaminases over un‑induced control was observed; instead, a trend toward normalization of ALT was noted. [1]
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| References | |
| Additional Infomation |
AL8697 is a selective p38α inhibitor designed through knowledge‑based optimization. Its chemical synthesis is described in Vidal et al. (2008) (patent WO2008/107125). Despite clear efficacy in preclinical studies, p38 inhibitors as a class have shown limited efficacy and toxicity in human rheumatoid arthritis trials. The compound’s profile in AIA showed marked anti‑inflammatory properties, moderate to marked disease‑modifying antirheumatic drug (DMARD) effects, moderate anti‑cachectic effects, and slight pro‑cholesterolemic effects, but no immunosuppressive properties. The authors hypothesise that the clinical failure of p38 inhibitors may be due to pleiotropic functions, class‑dependent side effects limiting the maximum tolerated dose, and species‑specific roles of p38 MAPK. [1]
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| Molecular Formula |
C21H21F3N4O
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|---|---|
| Molecular Weight |
402.412854909897
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| Exact Mass |
402.167
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| CAS # |
1057394-06-5
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| PubChem CID |
25060093
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| Appearance |
White to off-white solid powder
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| LogP |
4.702
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
626
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZVBTZTQYHOXIBC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21F3N4O/c1-10-13(7-11(8-14(10)22)19(29)25-12-5-6-12)16-15(23)9-28-18(17(16)24)26-27-20(28)21(2,3)4/h7-9,12H,5-6H2,1-4H3,(H,25,29)
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| Chemical Name |
3-(3-tert-butyl-6,8-difluoro-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-N-cyclopropyl-5-fluoro-4-methylbenzamide
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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 : ~100 mg/mL (~248.50 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.21 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (6.21 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 25.0 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 | 2.4850 mL | 12.4251 mL | 24.8503 mL | |
| 5 mM | 0.4970 mL | 2.4850 mL | 4.9701 mL | |
| 10 mM | 0.2485 mL | 1.2425 mL | 2.4850 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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