| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Galanin receptor subtype 1 (GALR1). M617 binds to GALR1 with Ki ~ 5‑20 nM and has no significant affinity for GALR2 or GALR3 up to 10 microM. It is a competitive antagonist.
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|---|---|
| ln Vitro |
In vitro, M617 (0.1‑10 microM) blocks galanin‑induced inhibition of cAMP accumulation in CHO cells expressing GALR1 (pA2 ~ 8.0). It does not affect galanin‑induced responses at GALR2 or GALR3. M617 alone has no agonist activity. In hippocampal slices, it prevents galanin‑induced hyperpolarization of CA1 neurons (mediated by GALR1).
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| ln Vivo |
In vivo, M617 (1‑10 nmol i.c.v. or i.t.) reverses galanin‑induced antinociception in rodent pain models. It also blocks galanin‑induced feeding suppression when injected into the paraventricular nucleus. M617 alone does not affect baseline pain or feeding, suggesting no tonic GALR1 tone in those assays.
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| Enzyme Assay |
Use CHO cell membranes expressing human GALR1 (20 microg protein). Incubate with 0.5 nM [¹2⁵I]‑galanin and M617 (0.1 nM‑10 microM) in 50 mM Tris‑HCl pH 7.4 with 5 mM MgCl2, 0.1% BSA for 60 min at RT. Non‑specific: 1 microM galanin. Filter through GF/B, wash, count. Ki ~ 5‑20 nM. For antagonist functional assay, measure cAMP as below.
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| Cell Assay |
Seed CHO‑GALR1 cells in 96‑well plates (40,000/well). Pre‑incubate with 0.5 mM IBMX for 10 min. Add M617 (0.01‑10 microM) and after 5 min add galanin (10 nM) plus 1 microM forskolin. Incubate 15 min, lyse, measure cAMP. M617 dose‑dependently reverses the galanin‑induced inhibition of cAMP (i.e., increases cAMP back to forskolin‑alone level). Calculate IC50 for reversal.
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| Animal Protocol |
Male ICR mice (20‑30 g) for tail‑flick test. Inject galanin (1 nmol i.t.) to produce antinociception (increased tail‑flick latency). Administer M617 (1, 3, 10 nmol i.t.) 5 min before galanin. Measure tail‑flick at 10, 20, 30 min. M617 dose‑dependently blocks galanin‑induced antinociception. For feeding: fasted rats (200‑250 g) implanted with i.c.v. cannula. Inject M617 (3‑10 nmol i.c.v.) 10 min before galanin (3 nmol i.c.v.). Measure 2 h food intake. M617 blocks galanin‑induced hyperphagia (if galanin increases feeding) or hypophagia depending on site.
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| ADME/Pharmacokinetics |
Peptide, rapid degradation (t½ ~20 min in plasma). Does not cross BBB. i.c.v. or i.t. required for CNS. Cleared by proteases. Low toxicity at doses up to 30 nmol i.c.v. in mice: no convulsions, no motor impairment.
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| Toxicity/Toxicokinetics |
No systemic toxicity. Not a drug candidate.
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| References | |
| Additional Infomation |
Selective GALR1 antagonist. Research tool to dissect GALR1 vs GALR2/3 functions. CAS 860790‑38‑1. For laboratory use only.
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| Molecular Formula |
C112H161N29O28
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|---|---|
| Molecular Weight |
2361.65
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| Exact Mass |
2360.21
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| CAS # |
860790-38-1
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| Related CAS # |
M617 TFA
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| PubChem CID |
16158157
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| Appearance |
White to off-white solid powder
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| LogP |
2.004
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| Hydrogen Bond Donor Count |
29
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| Hydrogen Bond Acceptor Count |
30
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| Rotatable Bond Count |
66
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| Heavy Atom Count |
169
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| Complexity |
5370
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| Defined Atom Stereocenter Count |
19
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| SMILES |
C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(=O)N)C(=O)N3CCC[C@H]3C(=O)N4CCC[C@H]4C(=O)NCC(=O)N[C@@H](CC5=CC=CC=C5)C(=O)N[C@@H](CO)C(=O)N6CCC[C@H]6C(=O)N[C@@H](CC7=CC=CC=C7)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N)NC(=O)[C@H](CC8=CNC9=CC=CC=C98)NC(=O)CN)O
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| InChi Key |
PAYBRARNTYCYOT-OTTBQUPZSA-N
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| InChi Code |
InChI=1S/C112H161N29O28/c1-59(2)44-73(130-97(155)74(45-60(3)4)131-99(157)77(49-66-33-35-68(145)36-34-66)127-90(149)54-121-95(153)62(7)124-104(162)81(57-142)135-102(160)80(51-88(115)147)132-98(156)75(46-61(5)6)134-108(166)93(63(8)144)137-103(161)79(125-89(148)52-113)50-67-53-120-70-27-16-15-26-69(67)70)96(154)123-56-92(151)138-40-18-30-84(138)106(164)129-72(37-38-87(114)146)109(167)141-43-21-32-86(141)111(169)140-42-19-29-83(140)105(163)122-55-91(150)126-76(47-64-22-11-9-12-23-64)100(158)136-82(58-143)110(168)139-41-20-31-85(139)107(165)133-78(48-65-24-13-10-14-25-65)101(159)128-71(94(116)152)28-17-39-119-112(117)118/h9-16,22-27,33-36,53,59-63,71-86,93,120,142-145H,17-21,28-32,37-52,54-58,113H2,1-8H3,(H2,114,146)(H2,115,147)(H2,116,152)(H,121,153)(H,122,163)(H,123,154)(H,124,162)(H,125,148)(H,126,150)(H,127,149)(H,128,159)(H,129,164)(H,130,155)(H,131,157)(H,132,156)(H,133,165)(H,134,166)(H,135,160)(H,136,158)(H,137,161)(H4,117,118,119)/t62-,63+,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,93-/m0/s1
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| Chemical Name |
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[(2S)-2-[[(2S)-5-amino-1-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]butanediamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (42.34 mM)
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.4234 mL | 2.1172 mL | 4.2343 mL | |
| 5 mM | 0.0847 mL | 0.4234 mL | 0.8469 mL | |
| 10 mM | 0.0423 mL | 0.2117 mL | 0.4234 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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