| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
D2/D3 Receptor
|
|---|---|
| ln Vitro |
MLL1 methyltransferase activity is specifically inhibited and MLL-r cell growth is preferentially inhibited by piribedil diHClide (0-160 μM, 7 days) [4]. By disrupting the MLL1-WDR5 connection, piribedil diHClide (0-160 μM, 4 days) specifically lowers H3K4 methylation in MLL-r cells (THP-1 and MV4; 11). Cell cycle arrest, apoptosis, and differentiation of MLL-r cells (THP-1 and MV4; 11) are induced by piribedil diHClide (0-160 μM, 4 days) [4].
|
| ln Vivo |
Piribedil diHClide (intraperitoneal injection, 5, 15, 40 mg/kg) can reduce L-DOPA-induced dyskinesia in a rat model of Parkinson's disease [2]. Pirbedil dihydrochloride (oral gavage, 4-5 mg/kg daily for 2 weeks) increases locomotor activity and reverses motor deficits in adult common marmosets [3]. Piribedil diHClide (150 mg/kg orally, daily for 21 days) inhibits MLL-r tumor growth and reduces MLL1 target gene expression in MV4;11 tumor xenografts [4].
|
| Enzyme Assay |
Targeting WT MLL for the treatment of MLL-r leukemia, which is highly aggressive and resistant to chemotherapy, has been shown to be a promising strategy. However, drug treatments targeting WT MLL are lacking. We used an in vitro histone methyltransferase assay to screen a library consists of 592 FDA-approved drugs for MLL1 inhibitors by measuring alterations in HTRF signal and found that Piribedil represented a potent activity. Piribedil specifically inhibited the proliferation of MLL-r cells by inducing cell-cycle arrest, apoptosis and myeloid differentiation with little toxicity to the non-MLL cells. Mechanism study showed Piribedil blocked the MLL1-WDR5 interaction and thus selectively reduced MLL1-dependent H3K4 methylation. Importantly, MLL1 depletion induced gene expression that was similar to that induced by Piribedil and rendered the MLL-r cells resistant to Piribedil-induced toxicity, revealing Piribedil exerted anti-leukemia effects by targeting MLL1. Furthermore, both the Piribedil treatment and MLL1 depletion sensitized the MLL-r cells to doxorubicin-induced apoptosis. Our study support the hypothesis that Piribedil could serve as a new drug for the treatment of MLL-r AML and provide new insight for further optimization of targeting MLL1 HMT activity.[4]
|
| Cell Assay |
Cell viability assay[4]
Cell Types: MLL-r AML cells (THP-1 and MV4;11), non-MLL leukemia cell line (K562) Tested Concentrations: 0, 20, 40, 80 and 160 μM Incubation Duration: 0- 7 Experimental Results: Inhibited the growth rate of THP-1 and MV4;11 cells in a time-dependent manner. Western Blot Analysis[4] Cell Types: THP-1 and MV4; 11 cells Tested Concentrations: 0, 20, 40, 80 and 160 μM Incubation Duration: 4 days Experimental Results: H3K4me2 and H3K4me3 levels were diminished, but did not affect other histones Methylation, such as H3K79, H3K36 and H3K27. |
| Animal Protocol |
Animal/Disease Models: Parkinson's disease rat model [2]
Doses: 5, 15, 40 mg/kg Route of Administration: intraperitoneal (ip) injection, 5 minutes before levodopa administration. Experimental Results: Rotational behavior as well as AD (axial dystonia), OD (oral dyskinesia) and FD (forelimb dyskinesia) were diminished at doses of 5 and 40 mg/kg. LD (dyskinesia) increased at 40 mg/kg. Animal/Disease Models: Adult common marmoset [3] Doses: 4-5 mg/kg Route of Administration: po (oral gavage), one time/day for 2 weeks Experimental Results: Improved alertness and vigilance, reversed MPTP in rostral and caudal stripes Down-regulation of protachykinin mRNA induced in the cyst. |
| References |
|
| Molecular Formula |
C16H20CL2N4O2
|
|---|---|
| Molecular Weight |
371.26
|
| Exact Mass |
334.119
|
| Elemental Analysis |
C, 51.76; H, 5.43; Cl, 19.10; N, 15.09; O, 8.62
|
| CAS # |
1451048-94-4
|
| Related CAS # |
Piribedil;3605-01-4;Piribedil hydrochloride;78213-63-5
|
| PubChem CID |
56972173
|
| Appearance |
Solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
24
|
| Complexity |
356
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl.Cl.C1=CN=C(N2CCN(CC3=CC=C4OCOC4=C3)CC2)N=C1
|
| InChi Key |
LTXWEVPOJXPWAD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H18N4O2.2ClH/c1-4-17-16(18-5-1)20-8-6-19(7-9-20)11-13-2-3-14-15(10-13)22-12-21-14;;/h1-5,10H,6-9,11-12H2;2*1H
|
| Chemical Name |
2-[4-(1,3-Benzodioxol-5-ylmethyl)-1-piperazinyl]pyrimidine Dihydrochloride
|
| Synonyms |
Piribedil 2HCl; Piribedil Dihydrochloride
|
| HS Tariff Code |
2934.99.03.00
|
| 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)
|
| Solubility (In Vitro) |
DMSO: > 10 mM
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6935 mL | 13.4677 mL | 26.9353 mL | |
| 5 mM | 0.5387 mL | 2.6935 mL | 5.3871 mL | |
| 10 mM | 0.2694 mL | 1.3468 mL | 2.6935 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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