CWHM-12 is a potent inhibitor of αV integrins with IC50 values of 0.2, 0.8, 1.5, and 1.8 nM for αvβ8, αvβ3, αvβ6, and αvβ1, respectively. CWHM-12 demonstrates high potency against all of the five possible β subunit binding partners (αvβ1, αvβ3, αvβ5, αvβ6 and αvβ8) in in vitro ligand-binding assays.
In vivo, CWHM-12 significantly reduces liver fibrosis even after fibrotic disease have been established. Digital image quantitation demonstrates significantly reduced p-SMAD3 signaling in the livers of CWHM-12 treated mice compare to controls, demonstrating that the protection from CCl4-induced hepatic fibrosis observed in CWHM-12 treated mice is due at least in part to a reduction in TGF-β activation by αv integrins. Besides, administration of CWHM-12 significantly inhibited progression of pulmonary fibrosis.
Chin Med J (Engl). 2021 Apr 20;134(9):1093-1100.
Role of osteopontin in diet-induced brown gallstone formation in rats
CWHM-12 purchased from AbMole
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Source | Chin Med J (Engl) (2021). Figure 6. CWHM12 (Abmole Bioscience Inc, Houston, TX, USA) |
| Method | Cell culture | |
| Cell Lines | BRL cell line | |
| Concentrations | - | |
| Incubation Time | 1 h | |
| Results | TNF-a content differed between the groups (F = 1041, P < 0.01), with the OPN group showing a significant elevation compared with normal saline (t = 56.59, P < 0.01), the CWHM12 + OPN group showing a significant reduction compared with the OPN group (t = -44.21, P < 0.01), and the CD44-Ab + OPN group showing a significant reduction, relative to both OPN (t = -23.63, P < 0.01) and NS-IgG + OPN groups (t = -18.40, P < 0.01). |
| Cell Experiment | |
|---|---|
| Cell lines | The stably transfected human 293 cells over-expressing human αvβ3 or αvβ5 |
| Preparation method | The stably transfected human 293 cells over-expressing human αvβ3 or αvβ5 are pre-incubated in HBSS buffer containing 200 μM MnCl2 for 30 min at 37°C with 3-fold dilutions of compound (e.g., CWHM-12). Each sample is then added to triplicate wells of a 96-well plate which has been coated overnight at 4°C with a predetermined optimal concentration of purified vitronectin, washed, blocked by 1 hr incubation with BSA, and washed again. Cells are allowed to attach for 30 min at 37°C, and non-adherent cells are removed by washing. Remaining attached cells are measured by endogenous alkaline phosphatase activity using para-nitrophenyl phosphate and reading absorbance signal at 405 nM. |
| Concentrations | |
| Incubation time | 90 min |
| Animal Experiment | |
|---|---|
| Animal models | Wild type C57/BL6 mice, Itgav(flox/flox) mice and itgb8(flox/flox) mice |
| Formulation | 50% DMSO (in sterile water) |
| Dosages | 100 mg/kg/day |
| Administration | delivered by implantable ALZET osmotic minipumps |
| Molecular Weight | 590.47 |
| Formula | C26H32BrN5O6 |
| CAS Number | 1564286-55-0 |
| Solubility (25°C) | DMSO: 10 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Integrin Products |
|---|
| HSDVHK-NH2
HSDVHK-NH2 is an antagonist of the integrin αvβ3-vitronectin interaction, with an IC50 of 1.74 pg/mL (2.414 pM). |
| LDV
LDV, a tripeptide, is a non-fluorescent analog of LDV-FITC. |
| Cyclo(RADfK)
Cyclo(RADfK) is a selective α(v)β(3) integrin ligand that has been extensively used for research, therapy, and diagnosis of neoangiogenesis. |
| Obtustatin
Obtustatin is a non-RGD disintegrin of 41 residues. |
| Integrin Binding Peptide
Integrin Binding Peptide is derived by fibronectin. |
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