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| Targets |
CCT 365623 targets lysyl oxidase (LOX), a copper-dependent amine oxidase that cross-links collagen and elastin in the extracellular matrix. LOX plays a critical role in tumor progression by regulating EGFR cell surface retention, and its inhibition by CCT 365623 disrupts this process.
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| ln Vitro |
In biosensor systems, CCT365623 suppresses LOX at a concentration of around 5 μM [1]. Surface EGFR protein levels are concentration-dependently decreased by CCT365623 (0-40 μM) [1]. The protein levels of pY1068 EGFR, pAKT, and MATN2 are decreased by CCT365623 (5 μM), but the protein level of pSMAD2 is increased [1]. Inhibiting EGFR surface retention, inhibiting MATN2 expression, inhibiting TGFβ1 signaling, disrupting HTRA1 multimerization, and inhibiting EGFR signaling are all caused by CCT365623 [1].
In vitro, CCT 365623 inhibits LOX activity in a living cell biosensor system at approximately 5 μM. It decreases surface EGFR protein levels in a concentration-dependent manner (0-40 μM), disrupts HTRA1 multimerization, activates TGFβ1 signaling, suppresses MATN2 expression, and reduces EGFR surface retention and signaling. At 5 μM, it decreases pY1068 EGFR, pAKT, and MATN2 protein levels while increasing pSMAD2. |
| ln Vivo |
In mouse liver microsomes, CCT365623 has good stability and does not block the hERG cardiac potassium channel[1]. In rats, CCT365623 (70 mg/kg, once daily oral gavage) greatly slowed the growth of primary tumors and reduced the burden of lung metastases. The EGFR cell surface retention is disrupted and the proliferation of primary and metastatic tumor cells is slowed down by CCT365623 [1]. T1/2PO for CCT365623 is 0.6 hours, and its oral bioavailability (F%) is 45%[1].
In vivo, CCT 365623 (70 mg/kg, oral gavage once daily) significantly delays the development of primary tumors and suppresses metastatic lung burden in animal models. It disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumor cells. |
| Enzyme Assay |
In vitro enzyme assays for LOX inhibition typically use a biosensor system or purified LOX enzyme with a suitable substrate. The compound is incubated with the enzyme at varying concentrations, and LOX activity is measured by detecting hydrogen peroxide production or using an Amplex Red-based assay. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Western blot analysis[1]
Cell Types: MDA-MB-231 cells. Tested Concentrations: 0-40 μM. Incubation Duration: 24 hrs (hours) Experimental Results: Dramatically diminished protein levels of surface EGFR, pY1068 EGFR, pAKT and MATN2. Increased protein levels of pSMAD2. In vitro cellular assays typically use cancer cell lines or MDCK cysts treated with CCT 365623 at various concentrations (0-40 μM). EGFR surface levels are measured by cell surface biotinylation followed by Western blotting. Phosphorylation of EGFR (pY1068) and AKT is assessed by Western blot. TGFβ1 signaling is evaluated by measuring pSMAD2 levels. |
| Animal Protocol |
Animal/Disease Models: Mouse model (70 days old) of spontaneous breast cancer metastasis to the lungs [1].
Doses: 70 mg/kg. Route of Administration: Administer by po (oral gavage) daily for approximately 3 weeks. Experimental Results: MATN2 protein levels were Dramatically diminished in primary and metastatic lung tumors and were accompanied by the loss of EGFR on the plasma membrane of primary and metastatic tumor cells. In vivo animal studies typically use xenograft or orthotopic tumor models in immunocompromised mice. Animals are administered CCT 365623 orally at 70 mg/kg once daily. Primary tumor growth is monitored by caliper measurement, and metastatic lung burden is assessed by histological analysis or bioluminescence imaging. |
| ADME/Pharmacokinetics |
CCT 365623 exhibits an oral half-life (T1/2 PO) of 0.6 hours and an oral bioavailability (F%) of 45%. It is orally bioavailable with moderate systemic exposure. The compound is metabolized primarily in the liver, and its metabolites are excreted via the kidneys and bile.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of CCT 365623 would typically include acute and repeated-dose toxicity in rodents, as well as genotoxicity and safety pharmacology assessments. As a LOX inhibitor, potential off-target effects on extracellular matrix remodeling and wound healing should be monitored. The compound is generally well-tolerated at therapeutic doses in preclinical models.
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| References | |
| Additional Infomation |
CCT 365623 HCl is a research compound that functions as a potent, orally active lysyl oxidase (LOX) inhibitor. By inhibiting LOX, it disrupts EGFR cell surface retention and signaling, thereby delaying tumor growth and metastasis. The compound is available for research use only and is not approved for therapeutic applications.
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| Molecular Formula |
C18H18CLNO4S3
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|---|---|
| Molecular Weight |
443.9878
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| Exact Mass |
443.008
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| CAS # |
2126136-98-7
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| Related CAS # |
CCT365623;2126134-01-6
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| PubChem CID |
139266765
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| Appearance |
White to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
674
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].S(C1=C([H])C([H])=C(C([H])([H])N([H])[H])S1)(C1=C([H])C(C2C([H])=C([H])C([H])=C([H])C=2[H])=C([H])C(=C1[H])S(C([H])([H])[H])(=O)=O)(=O)=O
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| InChi Key |
MKBRQENFVVWIGU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H17NO4S3.ClH/c1-25(20,21)16-9-14(13-5-3-2-4-6-13)10-17(11-16)26(22,23)18-8-7-15(12-19)24-18;/h2-11H,12,19H2,1H3;1H
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| Chemical Name |
[5-(3-methylsulfonyl-5-phenylphenyl)sulfonylthiophen-2-yl]methanamine;hydrochloride
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| Synonyms |
365623 HCl CCT365623HClCCT-365623 HCl
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~563.08 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.68 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 (4.68 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 (4.68 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 | 2.2523 mL | 11.2615 mL | 22.5230 mL | |
| 5 mM | 0.4505 mL | 2.2523 mL | 4.5046 mL | |
| 10 mM | 0.2252 mL | 1.1262 mL | 2.2523 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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