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Purity: ≥98%
CWHM-12 is a novel potent small molecule inhibitor of αV integrins with IC50s of 1.8/0.8/1.5/0.2 nM for αvβ1/αvβ3/αvβ8. It is less potent on αvβ5(IC50=61 nM) and on inhibition on αIIbβ3/α2β1/α10β1. CWHM12 worked the same way to prevent fibrosis as the genetic deletion method, it also prevent the progression of existing fibrosis in the liver and lungs and reversed some of the damage caused by fibrosis to those organs. Pharmacological blockade of α(v)-containing integrins by CWHM 12 attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all α(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.
| ln Vitro |
Moreover, αvβ5 (IC50=61 nM) and αIIbβ3/α2β1/α10β1 (IC50>5000 nM) are weakly inhibited by CWHM-12 (CWHM 12). CWHM-12 demonstrated strong potency against all five potential β-subunit binding partners (αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8) in in vitro ligand binding assays, with a marginally lower potency against αvβ5 compared to other αv integrants. The efficiency of protein [1].
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| ln Vivo |
After three weeks of CCl4 treatment to establish fibrotic disease, mice are given either CWHM-12 (CWHM 12) or a vehicle for the last three weeks of CCl4. Even after fibrotic disease has been proven, CWHM-12 dramatically reduces liver fibrosis. The CWHM-12 treated mice showed protection from CCl4-induced hepatic fibrosis, at least partially because of less TGF-β activation by αv integrins, as shown by digital image quantitation, which significantly reduced p-SMAD3 signaling in the livers of treated mice compared to controls. Additionally, pulmonary fibrosis progression was markedly slowed down by CWHM-12 administration[1].
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| References |
[1]. Henderson NC, et al. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013 Dec;19(12):1617-24.
[2]. Basta J, Robbins L, Stout L, Prinsen MJ, Griggs DW, Rauchman M. Pharmacologic inhibition of RGD-binding integrins ameliorates fibrosis and improves function following kidney injury. Physiol Rep. 2020;8(7):e14329 |
| Molecular Formula |
C26H32BRN5O6
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| Molecular Weight |
590.47
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| CAS # |
1564286-55-0
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| SMILES |
OC1=CC(C(NCC(N[C@@H](CC(O)=O)C2=CC(Br)=CC(C(C)(C)C)=C2)=O)=O)=CC(NC3=NCC(O)CN3)=C1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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 Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.52 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 (3.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6936 mL | 8.4678 mL | 16.9357 mL | |
| 5 mM | 0.3387 mL | 1.6936 mL | 3.3871 mL | |
| 10 mM | 0.1694 mL | 0.8468 mL | 1.6936 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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 Depletion of the αv integrin on hepatic stellate cells protects mice from CCl4-induced hepatic fibrosis.Nat Med.2013 Dec;19(12):1617-24. |
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αv integrin depletion on hepatic stellate cells inhibits pro-fibrotic gene expression via a reduction in transforming growth factor beta (TGF-β) activation.Nat Med.2013 Dec;19(12):1617-24. |
 Global loss of αvβ3, αvβ5 or αvβ6 or conditional loss of αvβ8 on hepatic stellate cells does not protect mice from CCl4-induced hepatic fibrosis.Nat Med.2013 Dec;19(12):1617-24. |
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