Synonym
Tovinontrine; IMR-687; IMR 687; IMR687;
IUPAC/Chemical Name
6-{(3S,4S)-4-methyl-1-[(pyrimidin-2-yl)methyl]pyrrolidin-3-yl}-3-(oxan-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one
InChi Key
GWGNPYYVGANHRJ-GDBMZVCRSA-N
InChi Code
InChI=1S/C21H26N6O2/c1-14-10-26(13-19-22-5-2-6-23-19)11-16(14)17-12-27-18(21(28)25-17)9-24-20(27)15-3-7-29-8-4-15/h2,5-6,9,12,14-16H,3-4,7-8,10-11,13H2,1H3,(H,25,28)/t14-,16-/m1/s1
SMILES Code
O=C1C2=CN=C(C3CCOCC3)N2C=C([C@@H]4CN(CC5=NC=CC=N5)C[C@H]4C)N1
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
Shelf Life
>3 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:
Tovinontrine is a PDE9 inhibitor; IC50s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively.
In vitro activity:
To be determined
In vivo activity:
Tovinontrine specifically targets phosphodiesterase-9, leading to increased cellular cGMP levels and HbF production. In preclinical studies, tovinontrine demonstrated its efficacy in reducing red blood cell sickling, immune cell activation, and microvascular stasis in a mouse SCD model. Tovinontrine showed no central nervous system accumulation, genotoxicity, myelotoxicity, or adverse effects on fertility and fetal development.
Reference: Haematologica. 2020 Mar;105(3):623-631. https://pubmed.ncbi.nlm.nih.gov/31147439/
|
Solvent |
mg/mL |
mM |
| Solubility |
| Soluble in DMSO |
100.0 |
253.50 |
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
394.48
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. McArthur JG, Svenstrup N, Chen C, Fricot A, Carvalho C, Nguyen J, Nguyen P, Parachikova A, Abdulla F, Vercellotti GM, Hermine O, Edwards D, Ribeil JA, Belcher JD, Maciel TT. A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease. Haematologica. 2020 Mar;105(3):623-631. doi: 10.3324/haematol.2018.213462. Epub 2019 May 30. PMID: 31147439; PMCID: PMC7049346.
In vitro protocol:
To be determined
In vivo protocol:
1. McArthur JG, Svenstrup N, Chen C, Fricot A, Carvalho C, Nguyen J, Nguyen P, Parachikova A, Abdulla F, Vercellotti GM, Hermine O, Edwards D, Ribeil JA, Belcher JD, Maciel TT. A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease. Haematologica. 2020 Mar;105(3):623-631. doi: 10.3324/haematol.2018.213462. Epub 2019 May 30. PMID: 31147439; PMCID: PMC7049346.
1: Langer AL, Esrick EB. β-Thalassemia: evolving treatment options beyond transfusion and iron chelation. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):600-606. doi: 10.1182/hematology.2021000313. PMID: 34889443.
2: Makis A, Voskaridou E, Papassotiriou I, Hatzimichael E. Novel Therapeutic Advances in β-Thalassemia. Biology (Basel). 2021 Jun 18;10(6):546. doi: 10.3390/biology10060546. PMID: 34207028; PMCID: PMC8235056.
3: McArthur JG, Svenstrup N, Chen C, Fricot A, Carvalho C, Nguyen J, Nguyen P, Parachikova A, Abdulla F, Vercellotti GM, Hermine O, Edwards D, Ribeil JA, Belcher JD, Maciel TT. A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease. Haematologica. 2020 Mar;105(3):623-631. doi: 10.3324/haematol.2018.213462. Epub 2019 May 30. PMID: 31147439; PMCID: PMC7049346.
