Tisolagiline

Last updated

Tisolagiline
Tisolagiline.svg
Clinical data
Other namesKDS-2010; KDS2010; SeReMABI
Drug class Reversible monoamine oxidase B (MAO-B) inhibitor
Identifiers
  • (2S)-2-{{#parsoidfragment:2}}4-[4-(trifluoromethyl)phenyl]phenyl]methylamino]propanamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C17H17F3N2O
Molar mass 322.331 g·mol−1
3D model (JSmol)
  • C[C@@H](C(=O)N)NCC1=CC=C(C=C1)C2=CC=C(C=C2)C(F)(F)F
  • InChI=1S/C17H17F3N2O/c1-11(16(21)23)22-10-12-2-4-13(5-3-12)14-6-8-15(9-7-14)17(18,19)20/h2-9,11,22H,10H2,1H3,(H2,21,23)/t11-/m0/s1
  • Key:XCUXYNYVUMLDKH-NSHDSACASA-N

Tisolagiline (INN Tooltip International Nonproprietary Name; developmental code names KDS-2010, SeReMABI) is a potent, highly selective, and reversible monoamine oxidase B (MAO-B) inhibitor which is under development for the treatment of Alzheimer's disease and obesity. [1] [2] [3] [4] It is taken by mouth. [1] Tisolagiline is being developed by NEUROBiOGEN and Scilex Bio. [1] [2] As of December 2024, it is in phase 2 clinical trials for Alzheimer's disease and obesity. [1] [2]

In 2025, research suggested that KDS-2010 could also be used in recovery of spinal cord injuries. In these injuries, there is an excess of glia cells which protect the site but inhibit neural repair. Use of the MAO-B inhibitor in animal models resulted in improved neurological and locomotor abilities. [5] [6]

References

  1. 1 2 3 4 "KDS 2010". AdisInsight. 6 February 2025. Retrieved 24 February 2025.
  2. 1 2 3 "Delving into the Latest Updates on KDS-2010 with Synapse". Synapse. 23 January 2025. Retrieved 24 February 2025.
  3. ↑ Nam MH, Sa M, Ju YH, Park MG, Lee CJ (April 2022). "Revisiting the Role of Astrocytic MAOB in Parkinson's Disease". International Journal of Molecular Sciences. 23 (8): 4453. doi: 10.3390/ijms23084453 . PMC   9028367 . PMID   35457272. 4.4. KDS2010 A recently developed KDS2010, which is ~12,500-fold more selective to MAOB than MAOA, differentiates the role of MAOB from MAOA and reports that MAOB does not contribute to DA degradation [39]. KDS2010 is a potent (IC50 = 7.6 nM), and selective MAOB inhibitor named shows no known off-target effect (no other enzymes or channels causing >40% inhibition) or toxicity for 4 weeks of repeated dosing in non-human primates [16,41]. KDS2010 was turned out to be highly effective for alleviating the PD-related motor symptoms and PD-like pathology, including reactive astrogliosis, excessive astrocytic GABA, and nigrostriatal DAergic neuronal loss in multiple rodent models of PD [41]. Its clinical efficacy is still waiting to be tested in future studies.
  4. ↑ Duarte P, Cuadrado A, León R (2021). "Monoamine Oxidase Inhibitors: From Classic to New Clinical Approaches". Handbook of Experimental Pharmacology. 264: 229–259. doi:10.1007/164_2020_384. ISBN   978-3-030-68509-6. PMID   32852645. KDS2010 is a novel compound highly potent and selective reversible MAO-B inhibitor (Fig. 2). It has demonstrated learning and memory improvements, promotion of synaptic transmission, and reduction of astrogliosis and astrocytic GABA levels in APP/presenilin 1 mice (Park et al. 2019).
  5. ↑ "Scientists Identify Astrocytic "Brake" That Inhibits Spinal Cord Repair". Bioengineer. 11 September 2025. Retrieved 15 September 2025.
  6. ↑ "Neuroregeneration after Spinal Cord Injury Restored by MAOB Inhibition". Inside Precision Medicine. 12 September 2025. Retrieved 15 September 2025.
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