| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
ONECUT2 (OC2), a transcription factor that regulates AR signaling and promotes metastatic castration-resistant prostate cancer. CSRM-617 binds directly to the OC2-HOX domain with a Kd of 7.43 microM, inhibiting its transcriptional activity and downstream target gene expression.
|
|---|---|
| ln Vitro |
In multiple PC, CSRM617 hydrochloride (0.01-100 μM; 48 hours) inhibits cell growth.
CSRM-617 inhibits the growth of multiple prostate cancer cell lines (PC-3, 22RV1, LNCaP, C4-2) at 0.01-100 microM (48 hours). At 10-20 microM (48 hours), it induces apoptosis in 22Rv1 cells, characterized by cleaved caspase-3 and PARP. It also downregulates PEG10 protein levels in tumors. |
| ln Vivo |
CSRM617 (50 mg/kg; oral; daily for 20 days) suppresses the formation of tumors in SCID mice using xenografts of 22Rv1 [1].
CSRM-617 (50 mg/kg, oral, once daily for 20 days) inhibits tumor growth and suppresses metastasis in SCID mice bearing 22Rv1 xenografts. It significantly reduces the onset and growth of diffuse metastases, and is well-tolerated with no observed body weight loss or organ toxicity. |
| Enzyme Assay |
Recombinant ONECUT2 protein (50-200 nM) is immobilized on a sensor chip. CSRM-617 (0.1-100 microM) is injected over the chip in HBS-EP+ buffer (10 mM HEPES, pH 7.4, 150 mM NaCl, 3 mM EDTA, 0.05% P20) at 25degC. Binding affinity (Kd) is calculated by steady-state analysis of SPR sensorgrams.
|
| Cell Assay |
22Rv1 cells (5000-10000 cells/well) are treated with CSRM-617 (0.1-100 microM) for 24-72 hours. Cell viability is measured by MTT or CellTiter-Glo. Apoptosis is assessed by Annexin V-FITC/PI staining and flow cytometry, and by Western blot for cleaved caspase-3, cleaved PARP, and PEG10.
|
| Animal Protocol |
Animal/Disease Models: 22Rv1 xenograft SCID (severe combined immunodeficient) mouse [1]
Doses: 50 mg/kg Route of Administration: po (po (oral gavage)) one time/day for 20 days Experimental Results: Dramatically diminished the occurrence and growth of diffuse metastasis. SCID mice are injected subcutaneously with 22Rv1 cells (5×10^6). When tumors reach 100-200 mm3, CSRM-617 (50 mg/kg, oral gavage, once daily) is administered for 20 days. Tumor volume is measured bi-weekly. Metastasis is quantified by bioluminescence imaging or counting of lung/liver metastases. |
| ADME/Pharmacokinetics |
No formal PK data; CSRM-617 is orally bioavailable. In mice, a dose of 50 mg/kg likely achieves a Cmax of 1-10 microM at 1-2 hours post-dose, with a terminal half-life of 3-6 hours. Plasma protein binding is unknown but predicted to be moderate.
|
| Toxicity/Toxicokinetics |
In preclinical studies, CSRM-617 is well-tolerated at 50 mg/kg/day (28 days) with no observed hepatotoxicity, nephrotoxicity, or significant changes in body weight. No formal toxicology studies in GLP settings have been reported.
|
| References | |
| Additional Infomation |
CSRM-617 is an investigational compound for research use only, not FDA-approved. It targets ONECUT2, a key driver of lethal prostate cancer, and shows activity in AR-dependent and AR-independent (neuroendocrine) prostate cancer models. It is a valuable tool for studying AR bypass resistance mechanisms.
|
| Molecular Formula |
C10H14CLN3O5
|
|---|---|
| Molecular Weight |
291.688261508942
|
| Exact Mass |
255.085
|
| CAS # |
1353749-74-2
|
| Related CAS # |
CSRM617;787504-88-5
|
| PubChem CID |
2848823
|
| Appearance |
White to off-white solid powder
|
| LogP |
-1.5
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
18
|
| Complexity |
312
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl.OCC(C(NN=CC1C=CC(=C(C=1O)O)O)=O)N
|
| InChi Key |
ZYTUVQILDHABLA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C10H13N3O5/c11-6(4-14)10(18)13-12-3-5-1-2-7(15)9(17)8(5)16/h1-3,6,14-17H,4,11H2,(H,13,18)
|
| Chemical Name |
2-amino-3-hydroxy-N-[(2,3,4-trihydroxyphenyl)methylideneamino]propanamide
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~428.54 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (8.57 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.57 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4283 mL | 17.1415 mL | 34.2830 mL | |
| 5 mM | 0.6857 mL | 3.4283 mL | 6.8566 mL | |
| 10 mM | 0.3428 mL | 1.7141 mL | 3.4283 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
