Genz-644282
Based on 2 publication(s) in Google Scholar
Genz-644282 is a non-camptothecin topoisomerase I inhibitor, used for cancer research.
For research use only. We do not sell to patients.
- Purity: 99.13%
- CAS No.: 529488-28-6
- Formula: C22H21N3O5
- Molecular Weight:407.42
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Storage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Cell Cycle/DNA Damage Compound Library
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HY-L025
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HY-L158
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Publications Citing Use of MedChemExpress (MCE) Genz-644282
MoreAll Topoisomerase Isoforms
More
Biological Activity
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Topoisomerase I |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| KB 3-1 | IC50 |
0.022 μM
Compound: 6a
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Inhibitory concentration against KB/V-1 cells overexpress MDR1
Inhibitory concentration against KB/V-1 cells overexpress MDR1
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[PMID: 15689163] |
| KB 3-1 | IC50 |
0.0004 μM
Compound: 6a
|
Inhibitory concentration against KB3-1 cell line was determined
Inhibitory concentration against KB3-1 cell line was determined
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[PMID: 15689163] |
| KB 3-1 | IC50 |
0.4 nM
Compound: 6a
|
Inhibitory concentration against KB3-1 cell line was determined
Inhibitory concentration against KB3-1 cell line was determined
|
[PMID: 15689163] |
| P388 | IC50 |
0.07 μM
Compound: 6a
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Inhibitory concentration against camptothecin-resistant variant of P388 cell line was determined
Inhibitory concentration against camptothecin-resistant variant of P388 cell line was determined
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[PMID: 15689163] |
| P388 | IC50 |
0.0003 μM
Compound: 6a
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Inhibitory concentration against P388 cell line in mouse leukemia was determine
Inhibitory concentration against P388 cell line in mouse leukemia was determine
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[PMID: 15689163] |
| P388 | IC50 |
0.3 nM
Compound: 6a
|
Inhibitory concentration against P388 cell line in mouse leukemia was determine
Inhibitory concentration against P388 cell line in mouse leukemia was determine
|
[PMID: 15689163] |
| RPMI 8402 | IC50 |
0.25 μM
Compound: 6a
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Cytotoxicity against camptothecin-resistant RPMI 8402
Cytotoxicity against camptothecin-resistant RPMI 8402
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[PMID: 15689163] |
| RPMI 8402 | IC50 |
0.0003 μM
Compound: 6a
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Inhibitory concentration against lymphoblast RPMI 8402 cell line was determined
Inhibitory concentration against lymphoblast RPMI 8402 cell line was determined
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[PMID: 15689163] |
| RPMI 8402 | IC50 |
0.3 nM
Compound: 6a
|
Inhibitory concentration against lymphoblast RPMI 8402 cell line was determined
Inhibitory concentration against lymphoblast RPMI 8402 cell line was determined
|
[PMID: 15689163] |
Genz-644282 is a topoisomerase I inhibitor. Genz-644282 shows potent activities against 29 human tumor cell lines with IC50s ranging from 1.8 nM to 1.8 μM[1]. Genz-644282 suppresses the PPTP cell lines, with IC50s of 0.2-21.9 nM, and the mean IC50 value is 1.2 nM[2]. Genz-644282 is potent at trapping Top1-DNA covalent cleavage complexes. Genz-644282 (0.1 μM) induces γH2AX foci in human colon cancer HCT116 cells and breast cancer MCF7 cells. Genz-644282 is cytotoxic on the CPT-resistant human cancer cell lines[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 529488-28-6
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Appearance Solid
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Molecular Weight 407.42
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Formula C22H21N3O5
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Color White to light brown
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SMILES
O=C1N(CCNC)C2=C(C=NC(C2=C3)=CC4=C3OCO4)C5=CC(OC)=C(OC)C=C15
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Publications (2)
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Journal Impact Factor
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Most Recent
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Commun Biol
Mechanism of action of non-camptothecin inhibitor Genz-644282 in topoisomerase I inhibition. [Abstract]2022 Sep 16;5(1):982. PMID: 36114357 -
J Mol Med (Berl)
2019 Aug;97(8):1183-1193. PMID: 31201471
Solvent & Solubility
DMSO : 3.64 mg/mL (8.93 mM; ultrasonic and warming and heat to 75°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Twenty-nine established human tumor cell lines are exposed to a concentration range of Genz-644282 in two-four independent experiments. Human tumor cell lines representing a range of histology and potential resistance mechanisms includ MIA PaCa-2, AsPC-1, BxPC-3, CFPAC-1, Hs766T and Capan-1 pancreatic cancers, MEL624, C32, Hs695T and SK-MEL-3 melanomas, NCI-H1299, NCI-H292, NCI-H1915 and SW900 non-small cell lung cancers, HCC1395, HCC1937, HCC202, Hs578T, T-47D and ZR-75-1 breast cancer, ACHN, 769-P, A-498, A-704, SW156, Caki-2 and TK-10 renal cancers and OVCAR-4 and OVCAR-5 ovarian cancers. Cells are plated at 4 × 103/well in 96-well tissue culture plates in 100 µL RPMI medium supplemented with 5% FBS and 12 concentrations of Genz-644282 from 0.1 nM to 10 µM, with each concentration tested in triplicate. Plates are incubated overnight at 37ºC in humidified air with 5% CO2. Plates are incubated with Genz-644282 at 37ºC with humidified air/5% CO2 for 72 hrs. After the incubation period, the test plates are read utilizing Cell Titer-Glo Luminescent Cell Viability Assay. Luminescence is measured with a Synergy HT plate reader utilizing the associated ineticalc software, Version #3.4. Luminescence data are converted to growth fraction by comparison to the luminescence for the untreated control for each cell line and IC50 and IC90 values determined from the graphical data. Each cell line is tested in t least two independent experiments[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Nu/nu mice are implanted subcutaneously with a 4 mm3 tumor fragment, and treatments are initiated when tumors reach 200 mm3. Compounds are prepared freshly prior to injection, with Genz-644282 is formulated in M/6 lactate, irinotecan in D5W (5% Dextrose, aqueous), gemcitabine in saline, and docetaxel in ethanol, Cremophor EL and saline. Genz-644282 is compared with irinotecan in experiments with the human HCT-116, HT-29, HCT-15 and DLD-1 colon carcinoma and 786-O renal cell carcinoma xenografts. Irinotecan is administered at 60 mg/kg/day by IV injection every fourth day for three injections. Genz-644282 is compared with docetaxel in the human CIH460 non-small cell lung carcinoma xenograft. Docetaxel is administered at 12, 16 or 20 mg/kg/day by IV injection on alternate days for three injections. Genz-644282 is compared with dacarbazine in the human LOX-IMVI melanoma xenograft. Dacarbazine is administered at 90 mg/kg/day by IP injection once daily for 5 days. Genz-644282 is administered at 1, 1.36, 1.7, 2.7 or 4.1 mg/kg/day by IV on alternate days 3-times per week for 2 weeks in all in vivo experiments[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Kurtzberg LS, et al. Genz-644282, a novel non-camptothecin topoisomerase I inhibitor for cancer treatment. Clin Cancer Res. 2011 May 1;17(9):2777-87. [Content Brief]
[2]. Houghton PJ, et al. Testing of the topoisomerase 1 inhibitor Genz-644282 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Feb;58(2):200-9. [Content Brief]
[3]. Sooryakumar D, et al. Molecular and cellular pharmacology of the novel noncamptothecin topoisomerase I inhibitor Genz-644282. Mol Cancer Ther. 2011 Aug;10(8):1490-9. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4545 mL | 12.2723 mL | 24.5447 mL | 61.3617 mL |
| 5 mM | 0.4909 mL | 2.4545 mL | 4.9089 mL | 12.2723 mL |
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