Shirt a Phobia

Sample Page

BMB-101 is a selective serotonin 5-HT2C receptor agonist of the phenylcyclopropylmethylamine (PCPMA) family which is under development for the treatment of absence epilepsy, binge-eating disorder, Dravet syndrome, Lennox–Gastaut syndrome, Pitt–Hopkins syndrome, Prader–Willi syndrome, and Rett syndrome.[1][2][3][4][5] It is taken orally.[1]

Pharmacology

Pharmacodynamics

BMB-101 activities
Target Affinity (Ki, nM)
5-HT2A ND (Ki)
2,280 (EC50Tooltip half-maximal effective concentration)
ND (EmaxTooltip maximal efficacy)
5-HT2B ND (Ki)
>10,000 (EC50)
ND (Emax)
5-HT2C ND (Ki)
Gq: 16 (EC50)
βarr1: 75 (EC50)
βarr2: 77 (EC50)
Gq: ~100% (Emax)
βarr1: 13% (Emax)
βarr2: 21% (Emax)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [3][4][5][6]

BMB-101 acts as a highly selective biased agonist of the serotonin 5-HT2C receptor.[1][7][3][5] It has greater that 100-fold selectivity for the serotonin 5-HT2C receptor over other serotonin receptors, including the serotonin 5-HT2A and 5-HT2B receptors.[3][5] In addition, the drug shows no significant activity at other serotonin receptors.[6] BMB-101 shows functional selectivity at the serotonin 5-HT2C receptor for activation of Gq signaling with minimal β-arrestin recruitment.[7][3][5] This in turn appears to minimize receptor desensitization and development of tolerance.[7][3] Due to its much greater selectivity for the serotonin 5-HT2C receptor, BMB-101 is not expected to possess the psychedelic effects or cardiotoxicity that have been associated with existing drugs like fenfluramine and lorcaserin at therapeutic or supratherapeutic doses.[3][4][5] In accordance with its mechanism of action, BMB-101 produces anticonvulsant effects in animals.[4]

The activation of serotonin 5-HT2C receptors has been shown to reduce epileptic seizure activity by inhibiting T-type calcium channels (Cav3).[8] These calcium channels facilitate high frequency burst firing in principal neurons of the subiculum. This firing pattern is upregulated following status epilepticus, with these hyperactive neurons often serving as the initiation point for seizures.[9][10][11]

Chemistry

Lumocaserin structure.

The exact chemical structure of BMB-101 does not yet appear to have been disclosed.[1][2][12] However, it is known to be a 2-phenylcyclopropylmethylamine (PCPMA) derivative and to share structural commonalities with tranylcypromine.[5][12] Moreover, lumocaserin (INNTooltip International Nonproprietary Name; CAS no. 1656330-84-5), a serotonin 5-HT2C receptor agonist of the PCPMA scaffold described as an anticonvulsant,[13] has been patented by Bright Minds Biosciences-associated researchers including Alan Kozikowski and Jianjun Cheng.[14][15] Lumocaserin’s INN was registered in January 2026.[13] The pharmacology and synthesis of lumocaserin have been described.[16] Various structurally related serotonin 5-HT2C receptor agonists have also been studied and described by Kozikowski and colleagues.[16][17]

Research

BMB-101 is under development by Bright Minds Biosciences.[1][2] As of January 2026, it is in phase 2 clinical trials for the treatment of absence epilepsy, Dravet Syndrome, Lennox–Gastaut syndrome, Pitt–Hopkins syndrome, Prader–Willi syndrome, and Rett syndrome.[1][2] It is or was also under development for the treatment of binge-eating disorder and opioid use disorder, but no recent development has been reported for these indications.[1][2]

The drug has been found to increase REM sleep time by 90% (from 56 minutes to 107 minutes) without altering total sleep duration (9.1 hours vs. 8.9 hours) in people with absence seizures in a clinical study.[18]

See also

References

  1. ^ a b c d e f g h “BMB 101”. AdisInsight. 23 October 2024. Retrieved 30 October 2024.
  2. ^ a b c d e “Delving into the Latest Updates on BMB-101 with Synapse”. Synapse. 29 October 2024. Retrieved 30 October 2024.
  3. ^ a b c d e f g Vasilkevich A, Duan J, Smith M, McCorvy JD, Pedersen J (May 2024). BMB-101: A selective 5-HT2C agonist for the treatment of rare epilepsies (PDF). Seventeenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII), Madrid, Spain 5–8 May 2024.
  4. ^ a b c d Vasilkevich A, Lovera A, Duan J, Smith MA, McCorvy J, Pedersen JT (October 2024). Selective 5-HT2C Agonists for the Treatment of Rare Epileptic Disorders (PDF). Society for Neuroscience 2024 Annual Meeting (Chicago), Satellite NIH Forum, October 5–9.
  5. ^ a b c d e f g “Bright Minds Investor Deck” (PDF). Bright Minds Biosciences Inc. September 2024.
  6. ^ a b Vasilkevich A, Duan J, McDonald I, Sourbron J, Smith M, McCorvy J, et al. (7 December 2024). BMB-101 and Biased 5-HT2C Agonism: A Novel Approach for Sustained Epilepsy Management (PDF). American Epilepsy Society Meeting 2024. Archived from the original on 1 December 2024. BMB-101 was investigated at 5-HT2A/2B/2C receptors using Gq dissociation as measured by BRET. In this assay, BMB-101 is a potent 5-HT2C agonist (EC50 = 16.2 nM) with minimal activity at 5-HT2A (EC50 = 2280 nM) and 5-HT2B (EC50 > 10000 nM) receptors. BMB-101 was evaluated for recruitment of β-arr1 and β-arr2 as measured by BRET and compared to Lorcaserin. BMB-101 exhibits weak partial agonism of β-arr1 and β-arr2 recruitment (βarr1: EC50 = 75 nM; Emax = 12.9%; βarr2: EC50 = 77 nM; Emax = 20.8%) compared to Gq dissociation measured by BRET. Lorcaserin, on the other hand, is able to maximally recruit β-arr1 and β-arr2 (βarr1: EC50 = 52.8 nM; Emax = 100.3%; βarr2: EC50 = 24.1 nM; Emax = 107.4%). BMB-101 shows a greater preference for Gq dissociation agonist activity versus β-arr1 and β-arr2 recruitment activity compared to Lorcaserin, thus demonstrating Gq-biased agonism.
  7. ^ a b c “Bright Minds Biosciences Launches Phase 2 Trial of BMB-101 for Epilepsy”. Synapse. 14 September 2024. Retrieved 30 October 2024.
  8. ^ Petersen AV, Jensen CS, Crépel V, Falkerslev M, Perrier JF (2017). “Serotonin Regulates the Firing of Principal Cells of the Subiculum by Inhibiting a T-type Ca2+ Current”. Frontiers in Cellular Neuroscience. 11: 60. doi:10.3389/fncel.2017.00060. PMC 5339341. PMID 28326015.
  9. ^ Menendez de la Prida L, Gal B (June 2004). “Synaptic contributions to focal and widespread spatiotemporal dynamics in the isolated rat subiculum in vitro”. The Journal of Neuroscience. 24 (24): 5525–36. doi:10.1523/JNEUROSCI.0309-04.2004. PMC 6729319. PMID 15201325.
  10. ^ Su H, Sochivko D, Becker A, Chen J, Jiang Y, Yaari Y, et al. (May 2002). “Upregulation of a T-type Ca2+ channel causes a long-lasting modification of neuronal firing mode after status epilepticus”. The Journal of Neuroscience. 22 (9): 3645–55. doi:10.1523/JNEUROSCI.22-09-03645.2002. PMC 6758371. PMID 11978840.
  11. ^ Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R (2002). “On the origin of interictal activity in human temporal lobe epilepsy in vitro”. Science. 298 (5597): 1418–1421. Bibcode:2002Sci…298.1418C. doi:10.1126/science.1076510. PMID 12434059.
  12. ^ a b Vasilkevich A, Lovera A, Duan J, McDonald I, Collins SD, Pedersen JT (7 December 2025). Overview of Bright Minds Biosciences: Pioneering Serotonin Pharmacology (PDF). 2025 AES Annual Meeting, December 5–9, Atlanta, Georgia.
  13. ^ a b “International Nonproprietary Names for Pharmaceutical Substances (INN)” (PDF). WHO Drug Information. 39 (4): 1221. 2025.
  14. ^ “Cyclopropylmethanamines as selective 5-HT(2C) receptor agonists”. Google Patents. 27 January 2016. Retrieved 19 February 2026.
  15. ^ “Lumocaserin”. PubChem. Retrieved 19 February 2026.
  16. ^ a b Cheng J, Giguère PM, Onajole OK, Lv W, Gaisin A, Gunosewoyo H, et al. (February 2015). “Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents”. J Med Chem. 58 (4): 1992–2002. doi:10.1021/jm5019274. PMC 4834193. PMID 25633969. Routes to the 5-fluoro compounds are depicted in Scheme 2 […] These intermediates were separated using chiral preparative HPLC and then deprotected with HCl in diethyl ether to give both (−)- and (+)-enantiomers of compound 16a−16d. […] Scheme 2. Synthesis of 5-Fluoro Compoundsa […] Table 4. Efficacy and Selectivity Data of Compound 16a−16da,b […] (+)-16a […] Compound (+)-16a, bearing an n-propyl group, displayed an EC50 value of 11 nM at 5-HT2C and was 9-fold more potent than its 5-chloro analogue (+)-13b (EC50 = 103 nM). It showed a high degree of selectivity over 5-HT2B (EC50 = 1994 nM) and 5-HT2A (no activity). […] General Method C: Deprotection of N-Boc-Amines to Afford HCl Salts (13a, 13b, 13e−13g, 13i−13n, and 16a−16d). […]
  17. ^ Zhang G, Cheng J, McCorvy JD, Lorello PJ, Caldarone BJ, Roth BL, et al. (July 2017). “Discovery of N-Substituted (2-Phenylcyclopropyl)methylamines as Functionally Selective Serotonin 2C Receptor Agonists for Potential Use as Antipsychotic Medications”. J Med Chem. 60 (14): 6273–6288. doi:10.1021/acs.jmedchem.7b00584. PMC 7374938. PMID 28657744.
  18. ^ Meglio M (16 January 2026). “BMB-101 Heads for Registrational Trials Following Positive Phase 2 Data in Absence Seizures, Developmental Encephalopathies”. NeurologyLive. Retrieved 16 January 2026. Outside of seizure control, BMB-101 also demonstrated a positive impact on outcomes of sleep in treated patients. Treatment with BMB-101 increased REM sleep by approximately 90% (from 56.2 minutes at baseline to 106.7 minutes) without meaningfully changing total sleep duration (9.1 vs 8.9 hours), indicating that REM gains were independent of overall sleep time.