Synonym
TAK063, TAK 063, TAK-063, Balipodect
IUPAC/Chemical Name
1-(2-fluoro-4-(1H-pyrazol-1-yl)phenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one
InChi Key
KVHRYLNQDWXAGI-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H17FN6O2/c1-32-21-15-29(19-9-8-17(14-18(19)24)28-13-5-11-25-28)27-22(23(21)31)20-10-12-26-30(20)16-6-3-2-4-7-16/h2-15H,1H3
SMILES Code
O=C1C(C2=CC=NN2C3=CC=CC=C3)=NN(C4=CC=C(N5N=CC=C5)C=C4F)C=C1OC
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Balipodect (TAK-063) is a PDE10A inhibitor with IC50 of 0.30 nM; >15000-fold selectivity over other PDEs.
In vitro activity:
The half-maximal inhibitory concentration (IC50) value of TAK-063 for PDE10A2 was 0.30 nM, and the minimum IC50 value among the other 10 PDE families was 5500 nM for PDE4D2. Thus, the PDE10A2 selectivity of TAK-063 over other PDE family enzymes was more than 15000-fold. In vitro PDE10A2 selectivity of TAK-063 was further assessed by measuring its inhibitory or stimulatory activities against enzymes (Table 1) and receptors (Table 2) at Ricerca Biosciences (Concord, OH). More than 50% inhibition or stimulation by 10 μM of TAK-063 was considered as a significant response. TAK-063 did not induce a significant response in 91 target molecules, except for PDEs. These results indicate that TAK-063 is a potent and selective inhibitor of human PDE10A in vitro.
Reference: PLoS One. 2015; 10(3): e0122197. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376699/
In vivo activity:
TAK-063 showed significant improvement in overall recovery, with a difference in stroke + 3.0 mg/kg over the 9-week treatment compared with stroke + vehicle controls (Fig. 1a, n = 8–10 for each treatment group, P = 0.0129). TAK-063 did not enhance recovery of motor function in cortical stroke (Fig. 1b, n = 8–11, P = 0.9934). Overall, the results obtained from the Grid-Walking Task indicate that a daily dose of TAK-063 leads to improvement in gait and forelimb motor control in striatal stroke but not in cortical stroke. A separate behavioral test, the Cylinder Task, a measure of forelimb use in exploratory rearing, was also performed for both striatal and cortical stroke mice. The Cylinder test showed great variability between animals in motor performance and across time points. The stroke + 3.0 mg/kg dose of TAK-063 produced a tendency toward recovery of function in the affected forelimb in the striatal stroke over the 9-week treatment compared with stroke + vehicle controls (Supplementary Fig. 2A, P = 0.0558).
Reference: Transl Stroke Res. 2021; 12(2): 303–315. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644574/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
55.0 |
128.38 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
428.42
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Harada A, Suzuki K, Kamiguchi N, Miyamoto M, Tohyama K, Nakashima K, Taniguchi T, Kimura H. Characterization of binding and inhibitory properties of TAK-063, a novel phosphodiesterase 10A inhibitor. PLoS One. 2015 Mar 27;10(3):e0122197. doi: 10.1371/journal.pone.0122197. PMID: 25815469; PMCID: PMC4376699.
2. Birjandi SZ, Abduljawad N, Nair S, Dehghani M, Suzuki K, Kimura H, Carmichael ST. Phosphodiesterase 10A Inhibition Leads to Brain Region-Specific Recovery Based on Stroke Type. Transl Stroke Res. 2021 Apr;12(2):303-315. doi: 10.1007/s12975-020-00819-8. Epub 2020 May 6. Erratum in: Transl Stroke Res. 2020 Oct 29;: PMID: 32378029; PMCID: PMC7644574.
3. Tohyama K, Sudo M, Morohashi A, Kato S, Takahashi J, Tagawa Y. Pre-clinical Characterization of Absorption, Distribution, Metabolism and Excretion Properties of TAK-063. Basic Clin Pharmacol Toxicol. 2018 Jun;122(6):577-587. doi: 10.1111/bcpt.12964. Epub 2018 Feb 26. PMID: 29345044.
In vitro protocol:
1. Harada A, Suzuki K, Kamiguchi N, Miyamoto M, Tohyama K, Nakashima K, Taniguchi T, Kimura H. Characterization of binding and inhibitory properties of TAK-063, a novel phosphodiesterase 10A inhibitor. PLoS One. 2015 Mar 27;10(3):e0122197. doi: 10.1371/journal.pone.0122197. PMID: 25815469; PMCID: PMC4376699.
In vivo protocol:
1. Birjandi SZ, Abduljawad N, Nair S, Dehghani M, Suzuki K, Kimura H, Carmichael ST. Phosphodiesterase 10A Inhibition Leads to Brain Region-Specific Recovery Based on Stroke Type. Transl Stroke Res. 2021 Apr;12(2):303-315. doi: 10.1007/s12975-020-00819-8. Epub 2020 May 6. Erratum in: Transl Stroke Res. 2020 Oct 29;: PMID: 32378029; PMCID: PMC7644574.
2. Tohyama K, Sudo M, Morohashi A, Kato S, Takahashi J, Tagawa Y. Pre-clinical Characterization of Absorption, Distribution, Metabolism and Excretion Properties of TAK-063. Basic Clin Pharmacol Toxicol. 2018 Jun;122(6):577-587. doi: 10.1111/bcpt.12964. Epub 2018 Feb 26. PMID: 29345044.
1: Suzuki K, Harada A, Shiraishi E, Kimura H. In Vivo Pharmacological Characterization of TAK-063, a Potent and Selective Phosphodiesterase 10A Inhibitor with Antipsychotic-Like Activity in Rodents. J Pharmacol Exp Ther. 2015 Mar;352(3):471-9. doi: 10.1124/jpet.114.218552. Epub 2014 Dec 18. PubMed PMID: 25525190.
2: Kunitomo J, Yoshikawa M, Fushimi M, Kawada A, Quinn JF, Oki H, Kokubo H, Kondo M, Nakashima K, Kamiguchi N, Suzuki K, Kimura H, Taniguchi T. Discovery of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyri dazin-4(1H)-one (TAK-063), a highly potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor. J Med Chem. 2014 Nov 26;57(22):9627-43. doi: 10.1021/jm5013648. Epub 2014 Nov 10. PubMed PMID: 25384088.
Knott EP, Assi M, Rao SN, Ghosh M, Pearse DD. Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair. Int J Mol Sci. 2017 Mar 24;18(4):696. doi: 10.3390/ijms18040696. PMID: 28338622; PMCID: PMC5412282.
