| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
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| Other Sizes |
| Targets |
MMP-2 4 μM (IC50) MMP-9 20 μM (IC50)
MMP-2 (IC50 = 4 microM) and MMP-9 (IC50 = 20 microM). It is a reversible, competitive inhibitor of these type IV collagen-specific gelatinases, with approximately 5-fold selectivity for MMP-2 over MMP-9. |
|---|---|
| ln Vitro |
MMP-9 and MMP-2 can be inhibited by cis-ACCP, with IC50 values of 20 μM and 4 μM, respectively [1].
cis-ACCP is a reversible and competitive inhibitor of MMP-2 and MMP-9, with IC50 values of 4 microM and 20 microM, respectively. At a concentration of 100 uM, it prevents 90% of tumor cell invasion across Matrigel-coated membranes in vitro. Its activity is concentration-dependent, effectively blocking the degradation of type IV collagen, a key component of the basement membrane. |
| ln Vivo |
In mice, cis-ACCP (ip; 50, 250, 500 mg/kg; once daily for two weeks) decreased the growth of metastases and had no adverse consequences[1]. Circulating extracellular fluid is the only fluid in which cis-ACCP (oral, iv, ip; 50, 150 mg/kg) is dispersed[1].
In vivo, cis-ACCP is orally active and reduces metastasis formation in mice by approximately 90% when administered once daily at 50 mg/kg via the oral or intraperitoneal route. It is non-toxic at doses up to 500 mg/kg IP for two weeks. The compound distributes only into the extracellular fluid, the site of action for its antimetastatic activity. |
| Enzyme Assay |
For non-cellular assays, the recombinant human MMP-2 or MMP-9 enzyme is activated with APMA and then incubated in a standard MMP assay buffer with a fluorogenic substrate. cis-ACCP is added at varying concentrations (1-100 uM). The reaction is typically measured for 30-60 minutes. The IC50 values for the inhibition of each enzyme are calculated from the dose-response curves. A competitive inhibition assay can be performed to determine the Ki value.
|
| Cell Assay |
For cell-based assays, highly invasive cancer cell lines (e.g., HT-1080 fibrosarcoma or B16F10 melanoma) are seeded onto Matrigel-coated transwell inserts. The cells are treated with cis-ACCP (10-100 uM) and allowed to migrate towards a serum-containing chemoattractant for 24-48 hours. After the migration period, the non-migrating cells on the upper surface of the membrane are removed, and the migrated cells are fixed, stained, and counted. The percentage of invasion inhibition is calculated.
|
| Animal Protocol |
Animal/Disease Models: C57BL mice[1]
Doses: 50, 250, 500 mg/kg; 12.5 to 50 mg/kg Route of Administration: po (oral gavage) intraperitoneal, daily for two weeks; daily, 21 days Experimental Results: demonstrated no toxic effects and demonstrated 50- 85% inhibition of metastasis formation, depending on the dose. Animal/Disease Models: Rats[1] Doses: 50, 150 mg/kg Route of Administration: po (oral gavage) intravenous, intraperitoneal (ip) Experimental Results: demonstrated 84% of the intravenously (iv) administered drug are excreted unchanged. For animal studies, cis-ACCP is administered once daily by oral gavage or intraperitoneal (IP) injection to mice bearing highly metastatic tumors (e.g., B16F10 melanoma or colon carcinoma). Doses up to 500 mg/kg have been used for toxicity studies, while the anti-metastatic dose is typically 50 mg/kg. Treatment duration is usually 2-3 weeks. The primary endpoint is the number of metastatic nodules in the lungs (or other target organs) at the end of the study. |
| ADME/Pharmacokinetics |
Pharmacokinetic analysis in rats showed that cis-ACCP is rapidly absorbed from the gastrointestinal tract with a t1/2 of 126 min and achieves peak plasma concentrations (Cmax) of 712 ng/mL. The terminal elimination half-life (t1/2) from blood is approximately 18.8 minutes. The volume of distribution (Vss) is 186 mL/Kg, which is slightly lower than total body water, indicating that it is restricted to the extracellular fluid. Oral bioavailability (F) is low at 0.35%.
|
| Toxicity/Toxicokinetics |
cis-ACCP and its isomers have been shown to be non-toxic up to an intraperitoneal dose of 500 mg/kg over two weeks. No toxic side effects were observed at the anti-metastatic dose (50 mg/kg). The compound had no effect on the weight or survival of the mice. Its low oral bioavailability (0.35%) means that a significant amount of the drug remains in the gastrointestinal tract.
|
| References | |
| Additional Infomation |
cis-ACCP (cis-2-Aminocyclohexylcarbamoylphosphonic acid) is a first-in-class, orally active, antimetastatic MMP inhibitor developed by scientists at Tel Aviv University. It is a valuable research tool for studying MMP-2 and -9 in cancer and chronic diseases. The compound is not an approved drug. The trans isomer of ACCP does not inhibit MMPs but shows activity against MMP-3 and -13. cis-ACCP is a carbamoylphosphonate (CAP) compound with a molecular weight of 222.18 g/mol and a molecular formula of C7H15N2O4P.
|
| Molecular Formula |
C7H15N2O4P
|
|---|---|
| Molecular Weight |
222.18
|
| Exact Mass |
222.076
|
| CAS # |
777075-44-2
|
| PubChem CID |
44457233
|
| Appearance |
White to off-white solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.544
|
| LogP |
-2.04
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
14
|
| Complexity |
264
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1CC[C@H]([C@H](C1)N)NC(=O)P(=O)(O)O
|
| InChi Key |
XHCXISPZIHYKQD-NTSWFWBYSA-N
|
| InChi Code |
InChI=1S/C7H15N2O4P/c8-5-3-1-2-4-6(5)9-7(10)14(11,12)13/h5-6H,1-4,8H2,(H,9,10)(H2,11,12,13)/t5-,6+/m0/s1
|
| Chemical Name |
[(1R,2S)-2-aminocyclohexyl]carbamoylphosphonic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.5009 mL | 22.5043 mL | 45.0086 mL | |
| 5 mM | 0.9002 mL | 4.5009 mL | 9.0017 mL | |
| 10 mM | 0.4501 mL | 2.2504 mL | 4.5009 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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