Dersimelagon (MT-7117; WHO-10832) is a novel, oral and potent MC1R/melanocortin receptor agonist. It significantly boosted sunlight tolerance in patients with erythropoietic protoporphyria in a multicenter, phase 2 trial.
Physicochemical Properties
| Molecular Formula | C36H45F4N3O5 |
| Molecular Weight | 675.753224134445 |
| Exact Mass | 675.329 |
| CAS # | 1835256-48-8 |
| Related CAS # | 2490660-87-0 (phosphate);1835256-48-8; |
| PubChem CID | 126736894 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 3.1 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 48 |
| Complexity | 1110 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | F[C@]1(C(N2C[C@@H](COC)[C@H](C3=CC=C(C(F)(F)F)C=C3N3CCC(C(=O)O)CC3)C2)=O)CN(C[C@@H]1C1C=CC(=CC=1)OC)C1CCCC1 |
| InChi Key | MUNWOYRHJPWQNE-GMFUQMJFSA-N |
| InChi Code | InChI=1S/C36H45F4N3O5/c1-47-21-25-18-42(19-30(25)29-12-9-26(36(38,39)40)17-32(29)41-15-13-24(14-16-41)33(44)45)34(46)35(37)22-43(27-5-3-4-6-27)20-31(35)23-7-10-28(48-2)11-8-23/h7-12,17,24-25,27,30-31H,3-6,13-16,18-22H2,1-2H3,(H,44,45)/t25-,30+,31+,35+/m1/s1 |
| Chemical Name | 1-[2-[(3S,4R)-1-[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidine-3-carbonyl]-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl]piperidine-4-carboxylic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | In B16F1 cells, dersimelagon (0, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300 pM; 3 days) stimulates eumelanin synthesis in a concentration-dependent manner with an EC50 of 13 pM [1]. |
| ln Vivo | Ay/a mice's coat color darkens when dersimelagon (0.003, 0.03, 0.3, 3 mg/kg; orally administered for 6 days) is taken at dosages of 0.3 and 3 mg/kg [1]. In Ay/a mice, dersimelagon (0.03, 0.3, and 3 mg/kg; oral; single dose) increases Tyr, Trp1, and Dct expression at 24, 48, and 72 hours [1]. Cynomolgus monkeys administered with dersimelagon (1, 3, 10 mg/kg for 4 weeks; 30 mg/kg for 3 weeks; po) experience dose-dependent pigmentation induction that reverses upon stopping the medication [1]. |
| Animal Protocol |
Animal/Disease Models: cynomolgus monkey[1] Doses: 1, 3, 10, 30 mg/kg Route of Administration: oral; 1, 3, 10 mg/kg for 4 weeks, 30 mg/kg for 3 weeks Experimental Results: Based on dose Induces pigmentation in a dependent manner. The minimum effective dose for pigmentation is 1 mg/kg. Pigmentation diminished 4 weeks after cessation of treatment in the 1, 3 and 10 mg/kg groups, and 16 weeks after cessation of treatment in the 30 mg/kg group. |
| References |
[1]. Melanogenic effect of dersimelagon (MT-7117), a novel oral melanocortin 1 receptor agonist. Skin Health Dis. 2022; 2(1):e78. [2]. Porphyrias in the Age of Targeted Therapies. Diagnostics (Basel). 2021;11(10):1795. Published 2021 Sep 29. |
| Additional Infomation |
Dersimelagon is an orally bioavailable selective, non-peptide melanocortin-1 receptor (MC1R; melanocyte-stimulating hormone receptor; MSHR; melanin-activating peptide receptor; melanotropin receptor) agonist, that can potentially be used to prevent phototoxicity. Upon administration, dersimelagon targets, binds to and activates MC1R. This may prevent phototoxicity and related pain in erythropoietic protoporphyria (EPP) or X-Linked Protoporphyria (XLP) patients. MC1R, a G protein-coupled receptor that binds to melanocortins and are located on melanocytes, is involved in regulating mammalian skin and hair color. Drug Indication Treatment of erythropoietic protoporphyria, Treatment of X-linked protoporphyria |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4798 mL | 7.3992 mL | 14.7984 mL | |
| 5 mM | 0.2960 mL | 1.4798 mL | 2.9597 mL | |
| 10 mM | 0.1480 mL | 0.7399 mL | 1.4798 mL |