WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H414720
CAS#: 1224591-33-6 (free base)
Description: Simufilamum, also known as PTI-125, is a filamin A altered conformations binder. PTI-125 is an oral small molecule drug candidate that binds and reverses an altered conformation of the scaffolding protein filamin A found in Alzheimer's disease brain. PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis. PTI-125 also reduced tau hyperphosphorylation, aggregated Aβ42 deposition, neurofibrillary tangles, and neuroinflammation. Efficacy in postmortem AD and Aβ42-treated age-matched control hippocampal slices was concentration-dependent starting at 1 picomolar (pM) concentration. PTI-125 is the first therapeutic candidate to preferentially bind an altered protein conformation and reverse this proteopathy.
Hodoodo Cat#: H414720
Name: Simufilamum
CAS#: 1224591-33-6 (free base)
Chemical Formula: C15H21N3O
Exact Mass: 259.17
Molecular Weight: 259.350
Elemental Analysis: C, 69.47; H, 8.16; N, 16.20; O, 6.17
Related CAS #: 2480226-07-9 (HCl) 1224591-33-6 (free base) 2375909-85-4 (2HCl H2O) 2480226-06-8 (2HCl)
Synonym: simufilamum; simufilam; PTI125; PTI 125; PTI-125
IUPAC/Chemical Name: 1-benzyl-8-methyl-1,4,8-triazaspiro[4.5]decan-2-one
InChi Key: BSQPTZYKCAULBH-UHFFFAOYSA-N
InChi Code: InChI=1S/C15H21N3O/c1-17-9-7-15(8-10-17)16-11-14(19)18(15)12-13-5-3-2-4-6-13/h2-6,16H,7-12H2,1H3
SMILES Code: O=C1N(CC2=CC=CC=C2)C3(CCN(C)CC3)NC1
Appearance: 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: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
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
More Info:
| Biological target: | |
| In vitro activity: | |
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The following data is based on the product molecular weight 259.35 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: | |
| In vitro protocol: | |
| In vivo protocol: |
1: Wang HY, Pei Z, Lee KC, Lopez-Brignoni E, Nikolov B, Crowley CA, Marsman MR, Barbier R, Friedmann N, Burns LH. PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients. J Prev Alzheimers Dis. 2020;7(4):256-264. doi: 10.14283/jpad.2020.6. PMID: 32920628.
2: Zhang L, Huang T, Teaw S, Nguyen LH, Hsieh LS, Gong X, Burns LH, Bordey A. Filamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations. Sci Transl Med. 2020 Feb 19;12(531):eaay0289. doi: 10.1126/scitranslmed.aay0289. PMID: 32075941.
3: Wang HY, Lee KC, Pei Z, Khan A, Bakshi K, Burns LH. PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis. Neurobiol Aging. 2017 Jul;55:99-114. doi: 10.1016/j.neurobiolaging.2017.03.016. Epub 2017 Mar 31. PMID: 28438486.
4: Burns LH, Wang HY. Altered filamin A enables amyloid beta-induced tau hyperphosphorylation and neuroinflammation in Alzheimer's disease. Neuroimmunol Neuroinflamm. 2017;4(12):263-271. doi: 10.20517/2347-8659.2017.50. Epub 2017 Dec 8. PMID: 34295950; PMCID: PMC8294116.
5: Wang HY, Bakshi K, Frankfurt M, Stucky A, Goberdhan M, Shah SM, Burns LH. Reducing amyloid-related Alzheimer's disease pathogenesis by a small molecule targeting filamin A. J Neurosci. 2012 Jul 18;32(29):9773-84. doi: 10.1523/JNEUROSCI.0354-12.2012. Erratum in: J Neurosci. 2021 Dec 15;41(50):10405. Erratum in: J Neurosci. 2022 Jan 19;42(3):529. PMID: 22815492; PMCID: PMC6621293.
