1. Cell Cycle/DNA Damage
  2. Topoisomerase

Genz-644282 

Cat. No.: HY-16228 Purity: 98.00%
Handling Instructions

Genz-644282 is a non-camptothecin topoisomerase I inhibitor, used for cancer research.

For research use only. We do not sell to patients.

Genz-644282 Chemical Structure

Genz-644282 Chemical Structure

CAS No. : 529488-28-6

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 158 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
5 mg USD 144 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 264 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 624 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 1128 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

View All Topoisomerase Isoform Specific Products:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Genz-644282 is a non-camptothecin topoisomerase I inhibitor, used for cancer research.

IC50 & Target[1]

Topoisomerase I

 

In Vitro

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].

In Vivo

Genz-644282 (1-4 mg/kg) is active when administered intravenously to the mice. Genz-644282 (2.7 mg/kg, i.v.) causes tumor growth delay (TGD) of 34 days in the human HCT-116 colon cancer xenograft, 27 days in the human HT-29 colon carcinoma xenograft and mice bearing the NCI-H460 human non-small cell lung carcinoma. Genz-644282 (2 mg/kg, i.v.) results in a TGD of 33 days in the human HCT-15 colon carcinoma xenograft, and 28 days in mice bearing LOX-IMVI melanoma. Moreover, Genz-644282 (1 mg/kg, i.v.) leads to 14 days of TGD in mice bearing the DLD-1 human colon carcinoma xenograft. Genz-644282 (1.7 mg/kg, i.v.) also produces a TGD of 23 days in mice bearing 786-O tumors and 33 days in NCI-H1299 human non-small cell lung carcinoma xenograft[1]. Genz644282 at maximum tolerated dose (MTD, 4 mg/kg) results in maintained complete responses (MCR) in 6/6 evaluable solid tumor models. Genz644282 (2 mg/kg) induces CR or MCR in 3/3 tumor models and causes objective regressions in 7 of 17 (41%) models, but there are no objective responses at 1 mg/kg[2].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.4545 mL 12.2723 mL 24.5447 mL
5 mM 0.4909 mL 2.4545 mL 4.9089 mL
10 mM 0.2454 mL 1.2272 mL 2.4545 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Genz-644282 is formulated in M/6 lactate.

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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

407.42

Formula

C₂₂H₂₁N₃O₅

CAS No.

529488-28-6

SMILES

O=C1N(CCNC)C2=C(C=NC(C2=C3)=CC4=C3OCO4)C5=CC(OC)=C(OC)C=C15

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country or Region *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
Genz-644282
Cat. No.:
HY-16228
Quantity: