121062-08-6

Basic information

• Product Name: Melanotan II
• Synonyms: AC-NLE-CYCLO(-BETA-ASP-HIS-D-PHE-ARG-TRP-EPSILON-LYS-NH2);AC-NLE-CYCLO[(BETA-D)-HFRW-(EPSILON-K)]-NH2;AC-NLE-CYCLO(-ASP-HIS-D-PHE-ARG-TRP-LYS-NH2) ACETATE SALT;AC-NLE4-C[ASP5, D-PHE7, LYS10]ALPHA-MSH (4-10)-NH2;AC-[NLE4, ASP5, D-PHE7, LYS10]-ALPHA-MSH (4-10)-NH2;(AC-NLE4, ASP5, DPHE7, LYS10)-CYCLO-ALPHA-MSH (4-10) AMIDE;AC-NLE-ASP-HIS-D-PHE-ARG-TRP-LYS-NH2;AC-NLE-ASP-HIS-D-PHE-ARG-TRP-LYS-NH2, ASP5-LYS10, CYCLIC LACTAM
• CAS NO: 121062-08-6
• Molecular Formula: C₅₀H₆₉N₁₅O₉
• Molecular Weight: 1024.18
• EINECS: 1308068-626-2
• Product Categories: Amino Acid Derivatives;Peptide;Melanocortin receptor;Peptides
• Mol File: 121062-08-6.mol
• Article Data: 4

Chemical Properties

• Appearance: white/solid
• Density: 1.43
• Refractive Index: 1.669
• Storage Temp.: −20°C
• Solubility: H2O: 5 mg/mL, soluble
• PKA: 13.00±0.70(Predicted)
• CAS DataBase Reference: Melanotan II(CAS DataBase Reference)
• NIST Chemistry Reference: Melanotan II(121062-08-6)
• EPA Substance Registry System: Melanotan II(121062-08-6)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: OL4225000
• Hazardous Substances Data: 121062-08-6(Hazardous Substances Data)

Usage

Description

Melanotan II is a synthetic analogue of the melanocortin peptide hormone alpha-melanocyte stimulating hormone (α-MSH) that occurs naturally. In usage, Melanotan II has been revealed to have aphrodisiac and melanogenesis (tanning) effects that have been subjected to clinical trials and preliminary studies. The compound is a cyclic lactam analogue of α-MSH that has an amino sequence named MTII (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2). Notably, no government drug regulatory agency across the world had approved for the use of any compound incorporating the Melanotan II peptide by 2010

Historical Development

Melanotan II was first developed at the University of Arizona. Various studies conducted at the institution confirmed that the best defence against skin cancer was melanin activated in the skin, a tan. The researchers assumed that an effective procedure to reduce the rates of skin cancer in individuals would be by inducing the body’s natural pigmentary system to produce a tan that would be protective before exposure to UV. Melanogenesis is a process by which the skin’s pigment cells (melanocytes) produce the hormone α-MSH naturally causes the skin's pigment (melanin). After numerous clinical trials by administration of the endogenous hormone to the body, the scientists found that though it appeared to work, α-MSH had a very short half-life in the body to be practical as a therapeutic drug. Therefore, they opted to look for a more stable and potent alternative that would be more practical. Subsequently, after numerous trials, they developed Melanotan I and after that Melanotan II.

Uses

Different sources of media describe the Uses of 121062-08-6 differently. You can refer to the following data:
1. Malanotan II is used for tanning of the skin and producing of erections in men with erectile dysfunction when administered as a shot under the skin. Malanotan II is safe when used under strict medical supervision for treating erectile dysfunction. However, it may cause stomach cramps, tiredness, nausea, spontaneous erections of the penis, and darkened skin.
2. Melanotan II acetate salt has been used to study its inhibitory effects on feeding and energy expenditure in rats.
3. Melanotan II Acetic Acid Salt, is a lab-made chemical that is similar to a hormone found in people. Melanotan II has been shown to have melanogenesis (tanning) and aphrodisiac effects on humans.

BENEFITS OF A MELANOTAN II

Darker tan with less exposure to UV radiationTanning without sunburn, even for fair-skinned individualsPossible reduction in the risk of Melanoma (skin cancer)Possible reduction in the incidence of sun-damaged skinPossible reduction in body fatNo sunburn, n tan linesNo sunless tanning streaks or fake tan removalPossible increase libidoDuring clinical trials for its use as a tanning agent, melanotan II was found to be a potent stimulator of male erections. It has also been shown to increase female sexual desire in patients with sexual arousal disorder).

SIDE EFFECTS

Short term side effects after administration include:Facial flushingReduced appetite, nausea and vomitingIn males, spontaneous erections 1-5 hours after administration (priapism), associated with yawning and stretching complexLong term, there is concern that melanotan II may increase the risk of:Melanoma – a potentially serious form of skin cancerDeepening of the color of moles, new moles and atypical melanocytic naeviMelanonychia – brown to black discoloration of one or more nailsSuggested usage: daily for 1 - 2 weeks then one to two times weekly for maintenance.

Controversy

Melanotan II is widely sold online and in beauty salons as well as gyms as melanotan in their marketing. These products purport to contain the same chemical composition as afamelanotide. These products have been declared illegal and do not have the same chemical components as Melanotan II. As such, countries issues warnings against their use.

Dosage

Melanotan 2 has a half life of ~33 hours, this allows you to be very flexible with dosing. Recommended dosages start at 250mcg every day to help your body acclimatize to the peptide and minimize the side effects. You can continue with this dose indefinitely if you are intending to do a low dosage regimen.If you want to dose higher, after 2-4 days, whenever you feel comfortable, up the dose to 500mcg. 500mcg is the most common dosage amount administed by users. You can increase the dose as far as about 1mg but any higher is generally not advised and the users dosing 1mg/dose normally weigh around the 100kg mark.

General Description

Melanotan II induces melanogenesis and thus increases skin pigmentation. It is an analog of α-melanocyte stimulating hormone.

Biochem/physiol Actions

Melanotan II is a MC3-R/MC4-R melanocortin agonist.

Clinical Use

Melanotan II has been a new treatment for rosacea discussed in the various rosacea support groups on the internet. Melanotan I and Melanotan II are both analogs of the peptide hormone alpha-melanocyte stimulating hormone (a-MSH) that tend to induce skin tanning. Melanotan II has the additional effect of increasing libido. Melanotan II is an α-MSH analog which underwent clinical trials for the treatment of erectile dysfunction. Preliminary double-blind, placebo-controlled studies demonstrated the efficacy of melanotan in inducing penile erection in men with erectile dysfunction, although in a very restricted population.Unfortunately, there are no experimental data on the mode of action of melanotan II, as melanotan II is the first α-MSH agonist inducing penile erection when injected peripherally. Illustration of the proerectile effect of melanotan II (MT-II) in humans. Placebo (A) or MT-II (B, 25 ug/kg and C, 133 ug/kg) was injected subcutaneously in patients and RigiScan recording was performed from 6 h. Apparent erections developed in 8 of 10 men treated with MT-II. (Reproduced with permission from Wessells H et al. Effect of an alphamelanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology 2000; 56:641–646.)

Side effects

When given as a shot: Melanotan is POSSIBLY UNSAFE when given as a shot. It can causes nausea, stomachcramps, decreased appetite, flushing, tiredness, yawning, darkened skin, spontaneous erections of the penis, and other side effects. In some people, especially those with light skin, a change in the shape of moles, new moles, and skin cancer, have all occurred in people using melanotan.

InChI:InChI=1/C50H71N15O10/c1-3-4-16-36(59-29(2)66)44(70)65-41(25-42(67)68)49(75)64-40(24-32-27-55-28-58-32)48(74)62-38(22-30-13-6-5-7-14-30)46(72)61-37(19-12-21-56-50(53)54)45(71)63-39(23-31-26-57-34-17-9-8-15-33(31)34)47(73)60-35(43(52)69)18-10-11-20-51/h5-9,13-15,17,26-28,35-41,57H,3-4,10-12,16,18-25,51H2,1-2H3,(H2,52,69)(H,55,58)(H,59,66)(H,60,73)(H,61,72)(H,62,74)(H,63,71)(H,64,75)(H,65,70)(H,67,68)(H4,53,54,56)/t35-,36-,37-,38+,39-,40-,41-/m0/s1

Synthetic route

→ melanotan-II (121062-08-6)

Boc-Arg(Tos)-OH (13836-37-8) + Boc-Lys(Fmoc)-OH (84624-27-1) + Boc-D-Phe-OH (18942-49-9) + Nα-tert-butoxycarbonyl-1-formyl-L-tryptophan (47355-10-2) + Nα-Boc-His(Nϖ-Bom), Nα-Boc-Asp(β-Fmo), Nα-Boc-Nle, Ac2O → melanotan-II (121062-08-6)

Conditions	Yield
Yield given. Multistep reaction;

Boc-Arg(Tos)-OH (13836-37-8) + Boc-Lys(Fmoc)-OH (84624-27-1) + Boc-D-Phe-OH (18942-49-9) + Nα-Boc-Trp (Nin-MeS) (92916-47-7) + Nα-Boc-His (Nϖ-Bom), Nα-Boc-Asp (β-OFm), Nα-Boc-Nle, Ac2O → melanotan-II (121062-08-6)

Conditions	Yield
Multistep reaction;

Fmoc-Asp(ODmab)-OH; Dmab = 4-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl (269066-08-2) + acetic anhydride (108-24-7) + Fmoc-D-Phe-OH (86123-10-6) + Fmoc-His(Trt)-OH (109425-51-6) + Fmoc-(S)-2-aminohexanoic acid (77284-32-3) + Fmoc-Lys(Dde)-OH (150629-67-7) + 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester (143824-78-6) + Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine → melanotan-II (121062-08-6)

Conditions

Yield

Stage #1: Fmoc-Lys(Dde)-OH With 4-methyl-morpholine; benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide for 0.666667h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.416667h; Stage #3: Fmoc-Asp(ODmab)-OH; Dmab = 4-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl; acetic anhydride; Fmoc-D-Phe-OH; Fmoc-His(Trt)-OH; Fmoc-(S)-2-aminohexanoic acid; 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester; Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine Further stages;

...Expand

C94H103N14O14PolS + acetic anhydride (108-24-7) + Fmoc-(S)-2-aminohexanoic acid (77284-32-3) → melanotan-II (121062-08-6)

Conditions

Yield

Stage #1: C94H103N14O14PolS With piperidine; benzotriazol-1-ol In dichloromethane; N,N-dimethyl-d6-formamide at 20 - 75℃; for 0.1h; rink-amide-MBHA resin; Microwave irradiation; Stage #2: Fmoc-(S)-2-aminohexanoic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 75℃; for 0.0833333h; rink-amide-MBHA resin; Microwave irradiation; Stage #3: acetic anhydride Further stages;

Upstream product

• 13836-37-8 Boc-Arg(Tos)-OH 
• 84624-27-1 Boc-Lys(Fmoc)-OH 
• 18942-49-9 Boc-D-Phe-OH 
• 47355-10-2 Nα-tert-butoxycarbonyl-1-formyl-L-tryptophan 
• 92916-47-7 N^α-Boc-Trp (Nⁱⁿ-MeS) 
• 108-24-7 acetic anhydride 
• 77284-32-3 Fmoc-(S)-2-aminohexanoic acid 
• 269066-08-2 Fmoc-Asp(ODmab)-OH; Dmab = 4-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl 
• 86123-10-6 Fmoc-D-Phe-OH 
• 109425-51-6 Fmoc-His(Trt)-OH 
• 150629-67-7 Fmoc-Lys(Dde)-OH 
• 143824-78-6 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester 
• 187618-60-6 Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine 
• 117499-53-3 Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-NH₂ 

Relevant articles and documents

1,4-disubstituted-[1,2,3]triazolyl-containing analogues of MT-II: Design, synthesis, conformational analysis, and biological activity

Side chain-to-side chain cyclizations represent a strategy to select a family of bioactive conformations by reducing the entropy and enhancing the stabilization of functional ligand-induced receptor conformations. This structural manipulation contributes to increased target specificity, enhanced biological potency, improved pharmacokinetic properties, increased functional potency, and lowered metabolic susceptibility. The CuI-catalyzed azide-alkyne 1,3-dipolar Huisgen's cycloaddition, the prototypic click reaction, presents a promising opportunity to develop a new paradigm for an orthogonal bioorganic and intramolecular side chain-to-side chain cyclization. In fact, the proteolytic stable 1,4- or 4,1-disubstituted [1,2,3]triazolyl moiety is isosteric with the peptide bond and can function as a surrogate of the classical side chain-to-side chain lactam forming bridge. Herein we report the design, synthesis, conformational analysis, and functional biological activity of a series of i-to-i+5 1,4- and 4,1-disubstituted [1,2,3]triazole-bridged cyclopeptides derived from MT-II, the homodetic Asp5 to Lys10 side chain-to-side chain bridged heptapeptide, an extensively studied agonist of melanocortin receptors.

Microwave-assisted solid-phase synthesis of side-chain to side-chain lactam-bridge cyclic peptides

Side-chain to side-chain lactam-bridged cyclic peptides have been utilized as therapeutic agents and biochemical tools. Previous synthetic methods of these peptides need special reaction conditions, form side products and take longer reaction times. Herein, an efficient microwave-assisted synthesis of side-chain to side-chain lactam-bridge cyclic peptides SHU9119 and MTII is reported. The synthesis time and efforts are significantly reduced in the present method, without side product formation. The analytical and pharmacological data of the synthesized cyclic peptides are in accordance with the commercially obtained compounds. This new method could be used to synthesize other side-chain to side-chain lactam-bridge peptides and amenable to automation and extensive SAR compound derivatization.