CB03-154
| Clinical data | |
|---|---|
| Other names | CB-03; CB03; CB-003; CB003 |
| Routes of administration | Oral[1] |
| Drug class | Kv7.2 and Kv7.3 potassium channel opener |
| Identifiers | |
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| PubChem CID | |
| Chemical and physical data | |
| Formula | C23H27FN2O |
| Molar mass | 366.480 g·mol−1 |
| 3D model (JSmol) | |
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CB03-154 is a Kv7.2 and Kv7.3 potassium channel opener which is under development for the treatment of amyotrophic lateral sclerosis (ALS), epilepsy, major depressive disorder, bipolar disorders, stroke, and pain in China.[1][2][3][4][5] It is taken orally.[1][5] The drug is said to have higher selectivity and stability compared to retigabine.[4][6] CB03-154 is under development by Shanghai Zhimeng Biopharma.[1][2][4] As of November 2025, it is in 2/3 clinical trials for ALS, phase 2 trials for epilepsy and major depressive disorder, phase 1 trials for bipolar disorders, and the preclinical research stage of development for stroke, whereas no recent development has been reported for pain.[1][2]
See also
References
- ^ a b c d e "CB 03". AdisInsight. 6 November 2025. Retrieved 4 June 2026.
- ^ a b c "Delving into the Latest Updates on CB03-154 with Synapse". Synapse. 19 September 2024. Retrieved 4 June 2026.
- ^ Perucca E, Taglialatela M (March 2025). "Targeting Kv7 Potassium Channels for Epilepsy". CNS Drugs. 39 (3): 263–288. doi:10.1007/s40263-024-01155-3. PMC 11850491. PMID 39853501.
CB-003 or CB03, also known as CB03-154 or CB04 (N-(2-(4-fluorophenyl)−5,7-dimethyl-1,2,3,4-tetrahydro isoquinolin-6-yl)−2-(1-methylcyclopropyl) acetamide) is another Kv7.2/3 activator from China [169, 170]. Details on the pharmacology of this compound do not appear to have been published. The sponsor (Shanghai Zhimeng Biopharma) has completed a single and multiple-dose phase 1 safety, tolerability, and pharmacokinetic study in healthy subjects (NCT05502549) and a double-blind placebo-controlled safety and efficacy trial in patients with focal epilepsy is due to initiate in late 2024 (NCT06612775) [171]. CB-003 also received FDA orphan drug designation for amyotrophic lateral sclerosis [172].
- ^ a b c Martinez-Gonzalez L, Sanchez-Santos C, Huang CS, Gil C, Martinez A (May 2026). "Innovative therapies under clinical development for ALS treatment: small molecules". Expert Opinion on Investigational Drugs. 35 (5): 351–367. doi:10.1080/13543784.2026.2667249. hdl:10261/432424. PMID 42046889.
CB03-154, a selective voltage-gated potassium channel (KCNQ2/3) opener developed by Shanghai Zhimeng Biopharma, targets neuronal hyperexcitability in ALS with higher selectivity and stability compared to retigabine (withdrawn 2017 due to safety issues). Preclinical studies showed reduced hyperexcitability in iPSC motor neurons and extended survival in SOD1-ALS mice. Phase 1 trials in healthy volunteers (NCT05499260 US, NCT05502549 Australia) also showed promising safety/tolerability, supporting US orphan drug designation (October 2023) and China Center for Drug Evaluation (CDE) approval (July 2025). The phase 2/3 pivotal trial, which started late October 2025, is a multicenter, randomized, double-blind, placebo-controlled study with open-label extension enrolling ~240 ALS patients (disease duration <24 months) across 15 Chinese centers. The primary endpoint is change in ALSFRS-R from baseline at week 39 [47]. A US phase 2/3 trial (NCT07082192) is registered on ClinicalTrials.gov but has not yet started recruiting.
- ^ a b Zhu M, Hua B, Li B, Guo R, Liu G, Liu X, et al. (September 2024). "A Randomized, Double-Blind, Placebo-Controlled, Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of CB03-154 in Healthy Subjects". Annals of Neurology. 96: S179–S180.
- ^ Guo R, Hua B, Liang B, Liu G, Zhou X, Song C, et al. (September 2024). "Preclinical Overview of CB03-154 (KCNQ2/3 Channel Opener) for Amyotrophic Lateral Sclerosis (ALS)". Annals of Neurology. 96: S268–S269.