| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
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| ln Vitro |
In 5 of 8 leukemia and myeloma cell lines, less than 10 μM of PYZD-4409 (10–40 μM; 72 hours; myeloma, leukemia, and solid tumor cell lines, primary AML cells, and normal hematopoietic cells) results in cell death, or LD50. Solid tumor cell lines, on the other hand, have LD50s of roughly 15 to 20 μM, making them less susceptible. Compared to normal hematopoietic cells, PYZD-4409 primarily causes cytotoxicity against malignant cells [1]. PYZD-4409 (50 μM; 4 hours; K562 leukemia cells) treatment prevents ubiquitin from conjugating with the E2 enzyme cdc34 in an E1-dependent manner [1]. Grp78 and Hsp70 mRNA and protein levels were dramatically enhanced by PYZD-4409 (0-25 μM; 24 hours; K562 leukemia cells). Furthermore, phospho-JNK and phospho-p38 mitogen-activated protein kinases—which are linked to ER stress and the unfolded protein response—are also elevated by PYZD-4409 [1].
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| ln Vivo |
PYZD-4409 (10 mg/kg; i.p.; once everyday every other day for 16 days; male severe combination immunodeficient mice) decreases tumor weight and volume without adverse effects [1].
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| Cell Assay |
Cytotoxicity assay[1]
Cell Types: Myeloma, leukemia and solid tumor cell lines, primary AML cells and normal hematopoietic cells Tested Concentrations: 10 μM, 20 μM, 30 μM, 40 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induction of cell death Five of eight leukemia and myeloma cell lines had LD50s below 10 μM. In contrast, solid tumor cell lines are less sensitive, with LD50s of approximately 15 to 20 μM. Western Blot Analysis[1] Cell Types: K562 Leukemia Cells Tested Concentrations: 50 μM Incubation Duration: 4 hrs (hours) Experimental Results: Blocks E1-dependent conjugation of ubiquitin to the E2 enzyme cdc34. RT-PCR[1] Cell Types: K562 Cell Tested Concentrations: 0 μM, 10 μM, 25 μM Incubation Duration: 24 hrs (hours) Experimental Results: The mRNA and protein levels of Grp78 and Hsp70 were Dramatically increased. |
| Animal Protocol |
Animal/Disease Models: Male severe combined immunodeficiency (SCID) mice with MDAY-D2 murine leukemia cells [1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; daily, every other day; for 16 days Experimental Results: Delayed tumor growth , tumor weight was diminished without adverse toxicity. |
| References |
| Exact Mass |
351.006
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|---|---|
| CAS # |
423148-78-1
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| PubChem CID |
60111983
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| Appearance |
Light brown to black solid powder
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| LogP |
3.305
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
595
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=CC=C(N2C(/C(C(N2)=O)=C\C3=CC=C([N+]([O-])=O)O3)=O)C=C1Cl
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| InChi Key |
MSYMKEYWUWVZQY-TWGQIWQCSA-N
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| InChi Code |
InChI=1S/C14H7ClFN3O5/c15-10-5-7(1-3-11(10)16)18-14(21)9(13(20)17-18)6-8-2-4-12(24-8)19(22)23/h1-6H,(H,17,20)/b9-6-
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| Chemical Name |
(4Z)-1-(3-chloro-4-fluorophenyl)-4-[(5-nitrofuran-2-yl)methylidene]pyrazolidine-3,5-dione
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| Synonyms |
PYZD4409 PYZD-4409 PYZD 4409
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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 |
| 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 : ≥ 35 mg/mL (~99.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.11 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
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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