Volufralin
 | |
| Clinical data | |
|---|---|
| Other names | LIB-01; LIB01; DIC-2024; DIC2024; Libiguin |
| Routes of administration | Oral[1][2] |
| Drug class | Indirect melanocortin MC4 receptor potentiator |
| Pharmacokinetic data | |
| Onset of action | 15–120 min (Tmax[2] |
| Elimination half-life | ≪12 hours[2] |
| Identifiers | |
| |
| CAS Number | |
| Chemical and physical data | |
| Formula | C33H40O12 |
| Molar mass | 628.671 g·mol−1 |
Volufralin (INN;[3] developmental code names LIB-01, DIC-2024 and Libiguin) is an indirect melanocortin MC4 receptor potentiator which is under development for the treatment of erectile dysfunction and premature ejaculation.[1][4] It is taken orally.[2]
Pharmacology
[edit]The drug works by increasing expression of the melanocortin MC4 receptor and of its endogenous agonist in the brain.[4][5] In relation to this, its mechanism of action differs from that of earlier direct melanocortin receptor agonists like bremelanotide.[2][6] As such, the drug is described as a potential first-in-class medication.[2][6] Volufralin produces non-acute long-lasting pro-erectile effects in rodents and humans, with short-term dosing resulting in gradually increasing improvement that is then sustained for weeks despite cessation of dosing.[4][2][6][7][8] The pro-erectile effects of volufralin can be reversed by a melanocortin MC4 receptor antagonist in rodents.[4][5]
Chemistry
[edit]Volufralin is a semisynthetic analogue of alkaloids from Neobeguea mahafalensis root bark such as libiguin A and libiguin B.[8][9] Neobeguea mahafalensis has a long history of traditional use in Madagascar.[8] In 2014, libiguin A and B were discovered via isolation from the roots of the plant and were found to cause "profound enhancement of sexual activity" in rodents.[9][10] This specifically included having very high potency and a remarkably long-lasting duration in increasing mounting behavior in male rodents.[9]
History
[edit]Volufralin was originated by Uppsala University in Sweden and is under development by Dicot Pharma.[1] As of July 2026, it is in phase 2 clinical trials for erectile dysfunction and the preclinical research stage of development for premature ejaculation.[1] The mechanism of action of the drug of indirect melanocortin MC4 receptor potentiation was not initially disclosed, but was announced by its developer in December 2025.[4][5] The exact chemical structure of volufralin was not initially disclosed, aside from it being related to the libiguins.[1][8][9] However, in July 2026, the generic name of volufralin and its structure were published.[3]
See also
[edit]References
[edit]- 1 2 3 4 5 "LIB 01". AdisInsight. 26 December 2025. Retrieved 27 January 2026.
- 1 2 3 4 5 6 7 Padma-Nathan H, Rosen R, Forest C, Holmberg M, Gauffin C (12 August 2024). "(129) Results of a First-In-Human Trial of Lib-01, A Novel, First in Class Potential Oral ED Drug with Unique Pharmacodynamic Properties". The Journal of Sexual Medicine. 21 (Supplement_7) qdae167.127. doi:10.1093/jsxmed/qdae167.127. ISSN 1743-6095. Retrieved 27 January 2026.
LIB-01 is a novel and first in class, small molecule which is an analogue of the active component of a root bark long used in ethnopharmacology. This study reports the results of the first-in-human safety and erectile function study. [...] One participant reported a prolonged erection. [...] After oral dosing of LIB-01, at all dose levels and dosing regimens, high plasma concentrations were observed with a peak at 15 to 120 min. At 12 h, plasma levels were below 3 % of the peak for all dose groups. Erectile rigidity increased in the active drug group as measured by RigiScan® and self-reported improved erectile function (IIEF-EF domain score) was similarly observed in the active drug groups and was most pronounced in the 25 mg, od X 3 days group with a mean change in IIEF-EF domain score of 7.8 and RigiScan® RAU of 3.8 (+40%) and 3.4 (+122%) for tip and base, respectively. The majority of responders experienced the onset of improved erectile function within the first 7 days post-first dose and it remained until Day 28 (end of study). [...] LIB-01, a novel and first-in-class molecule, was safe and well tolerated in males when orally administered at single and multiple ascending doses ranging from 10 mg to 150 mg. In addition, erectile function improvements were demonstrated utilizing the IIEF-EF and RigiScan®. Most interestingly, a unique pharmacodynamic profile was observed with an onset within 7 days and a duration of action of at least 28 days. The long duration of action combined with the short plasma half-life point to a new MOA for potential use in ED therapy and one that would dramatically change the paradigm of management. A Phase 2a study has now been initiated.
- 1 2 "INN Proposed List 135". World Health Organization. 19 July 2026. Retrieved 21 July 2026.
volufralinum volufralin (1R,3aS,3a1R,5S,6aR,8R,9S,9aS,9bR,12aR,13S,14R)-1-(furan-3-carbonyl)-9a-hydroxy-13-(2-methoxy-2-oxoethyl)-1,5,8,14-tetramethyl-11-oxododecahydro-5H-3a,6a,8-(epiethane[1,1,2]triyl)-3a1,5-epoxycyclopenta[d]pyrano[2,3,4-fg][1,3]benzodioxocin9-yl 2-methylpropanoate indirect melanocortin MC4 receptor (MC4R) potentiator, erectile dysfunction [...] C33H40O12 1088920-71-1 [...]
- 1 2 3 4 5 Foster B (12 January 2026). "A new approach could radically change erectile dysfunction treatment". Drug Discovery News. Retrieved 27 January 2026.
- 1 2 3 "Dicot Pharma presents new research findings on the mechanism of action of LIB-01". Dicot Pharma. 7 December 2025.
- 1 2 3 Giuliano F, Padma-Nathan H, Rosen RC, Forest C, Holmberg M, Gauffin C (9 May 2025). "Early Clinical Development Program, Including Results of a First-In-Human Trial of Lib-01, A Novel, First in Class Potential Oral Erectile Dysfunction Drug with Unique Pharmacodynamic Properties". The Journal of Sexual Medicine. 22 (Supplement_2) qdaf077.083. doi:10.1093/jsxmed/qdaf077.083. ISSN 1743-6095. Retrieved 27 January 2026.
- ↑ Giuliano F, Gorny D, Razanakolona M, Behr-Roussel D, Assaly R, Gauffin C (5 February 2024). "(370) Overview of Nonclinical Studies of LIB-01, a Novel Promising Oral Drug Under Development for Treatment of Erectile Dysfunction". The Journal of Sexual Medicine. 21 (Supplement_1) qdae001.355. doi:10.1093/jsxmed/qdae001.355. ISSN 1743-6095. Retrieved 27 January 2026.
- 1 2 3 4 Razanakolona M, Bradesi C, Laurin M, Fugl-Meyer K, Behr-Roussel D, Giuliano F, et al. (1 November 2022). "Prolonged Pro-Erectile Facilitator Effect of Lib-01 in Anesthetized Wistar Rats". The Journal of Sexual Medicine. 19 (Supplement_4): S3. doi:10.1016/j.jsxm.2022.08.082. ISSN 1743-6109. Retrieved 27 January 2026.
- 1 2 3 4 Razafimahefa S, Mutulis F, Mutule I, Liepinsh E, Dambrova M, Cirule H, et al. (March 2014). "Libiguins A and B: novel phragmalin limonoids isolated from Neobeguea mahafalensis causing profound enhancement of sexual activity". Planta Medica. 80 (4): 306–314. Bibcode:2014PlMed..80..306R. doi:10.1055/s-0033-1360390. PMID 24549927.
- ↑ Grigorjeva L, Liepinsh E, Razafimahefa S, Yahorau A, Yahorava S, Rasoanaivo P, et al. (May 2014). "Semisynthesis of libiguin A and its analogues by trans-lactonization of phragmalin". The Journal of Organic Chemistry. 79 (9): 4148–4153. doi:10.1021/jo500318w. PMID 24716657.
